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ADP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation of serine residues of the E1 PDC component
-
-
ir
ATP + Ac-YHGHSMSDPGVSYR
ADP + [Ac-YHGHSMSDPGVSYR]phosphate
ATP + casein
ADP + casein phosphate
-
kidney enzyme, low activity
-
?
ATP + Pda1p subunit
ADP + phosphorylated Pda1p subunit
ATP + PDHA1
ADP + phosphorylated PDHA1
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
ATP + SMAD1/5/8 protein
?
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
ATP + [pyruvate dehydrogenase A1 (acetyl-transferring)]
ADP + [pyruvate dehydrogenase A1 (acetyl-transferring)] phosphate
-
-
-
?
additional information
?
-
ATP + Ac-YHGHSMSDPGVSYR
ADP + [Ac-YHGHSMSDPGVSYR]phosphate
-
-
-
?
ATP + Ac-YHGHSMSDPGVSYR
ADP + [Ac-YHGHSMSDPGVSYR]phosphate
-
recombinant enzyme
-
-
?
ATP + Ac-YHGHSMSDPGVSYR
ADP + [Ac-YHGHSMSDPGVSYR]phosphate
-
synthetic peptide substrate
-
-
?
ATP + Pda1p subunit
ADP + phosphorylated Pda1p subunit
-
the enzyme is the kinase of the Saccharomyces cerevisiae pyruvate dehydrogenase complex, which negatively regulates the complex by reversible phosphorylation of its Pda1p subunit, overview
-
-
?
ATP + Pda1p subunit
ADP + phosphorylated Pda1p subunit
-
the enzyme is the kinase of the Saccharomyces cerevisiae pyruvate dehydrogenase complex, which negatively regulates the complex by reversible phosphorylation of its Pda1p subunit, overview
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
pyruvate dehydrogenase kinase is a negative regulator in the mitochondrial pyruvate dehydrogenase complex and plays a pivotal role in controlling TCA cycle and cell respiration
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
-
-
-
ir
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
a small pocket in the N-terminal region of PDHK2 is involved in enzyme regulation, the pocket is formed by residues L53, Y157, Y80, S83, I111, R112, H115, S153, R154, I157, R158, I161
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
PDHK plays a key role in controlling the balance between glucose and lipid oxidation according to substrate supply, PDHK inhibition leads to increased PDH activity increasing glucose oxidation
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
PDK is involved in fatty acid metabolism
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation of E2-bound E1
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
PDK activity as component of the pyruvate dehydrogenase complex PDC binding the lipoyl domain of E2
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation of 3 serine residues of the E2 domain, isozyme-specific activity
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation of E2-bound E1, higher activity with reduced E2, enzyme stimulation reduces the amount of bound ADP
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation of serine residues of the E1 component of pyruvate dehydrogenase complex PDC
-
-
ir
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation of serine residues of the E1 PDC component
-
-
ir
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
the pyruvate dehydrogenase is a component of the pyruvate dehydrogenase complex, PDC
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
PDHK plays a key role in controlling the balance between glucose and lipid oxidation according to substrate supply, PDHK inhibition leads to increased PDH activity increasing glucose oxidation
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation by PDK inhibits the pyruvate dehydrogenase complex, PDK plays a regulatory role in glucose metabolism, PDK4 expression is regulated by hepatic nuclear factor 4 and peroxisome proliferator-activated receptor gamma coactivator, PGC-1alpha
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
PDH inactivation by phosphorylation at serine residues of the E1alpha component of the complex
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
PDK activity as component of the pyruvate dehydrogenase complex PDC binding the lipoyl domain of E2
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation of 3 serine residues of the E2 domain, isozyme-specific activity
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
Kd for ATP is 2.5 micromol, for ADP 10.6 micromol and for dichloroacetate 226 micromol
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
enzyme has an important role in control of glucose homeostasis
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation of 3 serine residues in the pyruvate dehydrogenase domain of the pyruvate dehydrogenase complex
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
-
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
-
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
-
-
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
-
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
-
PDHK4 inhibits the pyruvate dehydrogenase complex by phosphorylation during starvation, regulation mechanism, overview
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
-
-
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
-
PDHK2 is an integral component of pyruvate dehydrogenase complex tightly bound to the inner lipoyl-bearing domains L2 of the dihydrolipoyl transacetylase component E2 of pyruvate dehydrogenase complex
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
phosphorylation at Ser292 by PDK1
-
-
r
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
reversible phosphorylation of alpha2beta2-heterotetrameric pyruvate dehydrogenase complex, i.e. E1, phosphorylation at Ser292 within the active-site loop structure of E1alpha by PDK1. Substrate mutation of Asp295 to Ala, Asn, or Leu greatly reduces phosphorylation of Ser292, while mutation of Gly297 has relatively little effect. AtPDC E1alpha S298A mutant is phosphorylated by AtPDK. Activity of the enzyme with different substrate mutants, overview
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-
r
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
substrate is kinase-depleted pyruvate dehydrogenase complex from Zea mays
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
highly specific for the substrate
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
highly specific for the substrate
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
highly specific for the substrate
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
highly specific for the substrate
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
incorporates gamma-phosphate from ATP into E1-component of pyruvate dehydrogenase-complex alpha-subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
incorporates gamma-phosphate from ATP into E1-component of pyruvate dehydrogenase-complex alpha-subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
incorporates gamma-phosphate from ATP into E1-component of pyruvate dehydrogenase-complex alpha-subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
incorporates gamma-phosphate from ATP into E1-component of pyruvate dehydrogenase-complex alpha-subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
phosphorylation sites are 3 Ser-residues in the alpha-subunit, i.e. E1, MW 41000, of pyruvate dehydrogenase
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
phosphorylation sites are 3 Ser-residues in the alpha-subunit, i.e. E1, MW 41000, of pyruvate dehydrogenase
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
phosphorylation sites are 3 Ser-residues in the alpha-subunit, i.e. E1, MW 41000, of pyruvate dehydrogenase
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
beta-subunit harbors a regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
the 3 serine phosphorylation sites of the E1 subunit are specifically and with different activity phosphorylated by the 4 isozymes, overview: site 1 is preferably utilized by PDK2, site 2 by PDK3, and site 3 is exclusively utilized by PDK1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
isozyme PDK2 can phosphorylate free pyruvate dehydrogenase complex but bound dihydrolipoyl transacetylase enhances the rate up to 5000fold
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
isozyme PDK3 has a putative regulatory role of the pyruvate dehydrogenase complex in sperm
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
involved in regulation of mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
the 3 serine phosphorylation sites of the E1 subunit are specifically and with different activity phosphorylated by the 4 isozymes, overview: site 1 is preferably utilized by PDK2, site 2 by PDK3, and site 3 is exclusively utilized by PDK1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
recombinant hybrid enzyme of PDK1 and PDK2 phosphorylates site 3 with lower activity than the PDK1 homodimer
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
serine phosphorylation site 3 of subunit E1 is exclusively phosphorylated by isozyme PDK1, not by PDK2, which prefers site 1 over site 2
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
enzyme regulation in the heart depends on thyroid hormone and lipid status
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
enzyme regulates glucose oxidation by pyruvate dehydrogenase complex, isozyme PDHK1 is of more potential importance in adult heart than the other isozymes
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
high-fat feeding increases the expression of isozyme PDK2, but not of PDK4, hyperthyroidism increases the expression of both isozymes, physiological implications
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
high-fat feeding increases the expression of isozyme PDK2, but not of PDK4, hyperthyroidism increases the expression of both isozymes, physiological implications
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
incorporates gamma-phosphate from ATP into E1-component of pyruvate dehydrogenase-complex alpha-subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
optimum activity within a small range of ionic strength of 0.03-0.05 M
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
additional information
?
-
performs pH-dependent autophosphorylation on serine residues
-
-
?
additional information
?
-
-
performs pH-dependent autophosphorylation on serine residues
-
-
?
additional information
?
-
-
pyruvate dehydrogenase Asp295 plays an important role in stabilizing the active-site loop structure of the pyruvate dehydrogenase, facilitating transfer of the gamma-phosphate from ATP to the Ser residue at regulatory site one of E1alpha, substrate structure, overview
-
-
?
additional information
?
-
no autophosphorylation
-
-
?
additional information
?
-
-
no autophosphorylation
-
-
?
additional information
?
-
no autophosphorylation
-
-
?
additional information
?
-
-
no activity with histones of calf thymus type II-A
-
-
?
additional information
?
-
-
little, if any activity with casein of bovine kidney
-
-
?
additional information
?
-
-
no activity with histones of calf thymus type II-A, VI-S and VIII-S
-
-
?
additional information
?
-
-
no activity with glycogen synthase a and rabbit skeletal muscle phosphorylase b
-
-
?
additional information
?
-
-
no activity with glycogen synthase a and rabbit skeletal muscle phosphorylase b
-
-
?
additional information
?
-
-
no activity with glycogen synthase a and rabbit skeletal muscle phosphorylase b
-
-
?
additional information
?
-
-
no activity with glycogen synthase a and rabbit skeletal muscle phosphorylase b
-
-
?
additional information
?
-
-
no autophosphorylation
-
-
?
additional information
?
-
-
activity depends on the buffer system, the reduction status of the lipoyl groups and on the serine phosphorylation site of the E1 subunit of the pyruvate dehydrogenase complex used as substrate
-
-
?
additional information
?
-
-
PDK regulates the pyruvate dehydrogenase multienzyme complex activity
-
-
?
additional information
?
-
-
PDK4 is critically important in the starved state because it helps prevent hypoglycemia, the enzyme is part of the pyruvate dehydrogenase complex PDC, detailed overview and modeling of the complex regulation and the molecular mechanisms
-
-
?
additional information
?
-
-
peroxisome proliferator-activated receptors and insulin have regulatory functions in expression of isozymes PDK2 and PDK4, regulation mechanism
-
-
?
additional information
?
-
-
pyruvate dehydrogenase kinase is part of the pyruvate dehydrogenase complex, regulation and component interactions, PDK2 binds the inner lipoyl domain L2, preferably in dimeric form, overview
-
-
?
additional information
?
-
-
rapid upregulation of isozyme PDK4 in skeletal muscle after prolonged exercise, PDK activity is increased during prolonged exercise, physiologic/metabolic state, overview
-
-
?
additional information
?
-
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
?
additional information
?
-
-
the PDK/PDH pathway is reduced by 73% in non small cell lung carcinoma contributing to hypoxia-inducible factor-1 stability and aerobic glycolysis
-
-
?
additional information
?
-
-
a homodimer of pyruvate dehydrogenase kinase is an integral part of the pyruvate dehydrogenase complex, PDC, to which it is anchore primarily through the inner lipoyl-bearing domains L2 of transacetylase component, binding structure, catalytic cycle of PDHK and its translocation over the PDC surface is thought to be mediated by the symmetric and asymmetric modes, in which the PDHK dimer binds to two and one L2-domain(s), respectively, overview
-
-
?
additional information
?
-
-
hypoxia-inducible factor HIF-1, inducible e.g. by CoCl2, mediates the expression of PDK1, which inhibits the pyruvate dehydrogenase in the tricarboxylic cycle by phosphorylation, high PDK1 activity increases the ATP levels and prevents hypoxia-induced reactive oxygen species generation and apoptosis
-
-
?
additional information
?
-
-
PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate, regulation of the pyruvate dehydrogenase complex, PDK4 overexpression in association with type I diabetes
-
-
?
additional information
?
-
-
PDHK2 is required for binding to the inner lipoyl domain L2 of the dihydrolipoyl acetyltransferase of the pyruvate dehydrogenase complex
-
-
?
additional information
?
-
PDK isozymes are molecular switches that downregulate the pyruvate dehydrogenase complex PDC by reversible phosphorylation in mitochondria, L2 domain binding structure of isozyme PDK3, overview
-
-
?
additional information
?
-
-
PDK isozymes are molecular switches that downregulate the pyruvate dehydrogenase complex PDC by reversible phosphorylation in mitochondria, L2 domain binding structure of isozyme PDK3, overview
-
-
?
additional information
?
-
-
PDK4 expression is specifically regulated by retinoic acids, via retinoid receptors, and trichostatin A, an inhibitor of histone deacetylase
-
-
?
additional information
?
-
-
PDK4 is involved in metabolic changes after induction by high-fat/low carbohydrate diet, overview
-
-
?
additional information
?
-
-
phosphorylation of the pyruvate dehydrogenase complex PDC by the pyruvate dehydrogenase kinases PDK2 and PDK4 inhibits PDC activity, expression of the PDK genes is elevated in diabetes, leading to the decreased oxidation of pyruvate to acetyl-CoA, transcriptional regulation of the PDK4 gene by the estrogen-related receptors ERRalpha and ERRgamma, the ERRs are orphan nuclear receptors whose physiological roles include the induction of fatty acid oxidation in heart and muscle, overview
-
-
?
additional information
?
-
-
pyruvate dehydrogenase kinase isozymes are the molecular switch that down-regulates activity of the pyruvate dehydrogenase complex through reversible phosphorylation
-
-
?
additional information
?
-
-
interaction of PDK with L2 within the pyruvate dehydrogenase complex, overview
-
-
?
additional information
?
-
ligand binding by isozyme PDK1 involves the conserved Ser75
-
-
?
additional information
?
-
-
ligand binding by isozyme PDK1 involves the conserved Ser75
-
-
?
additional information
?
-
-
PD kinase isozymes PDK1, PDK2, PDK3 and PDK4, reduce the active form of pyruvate dehydrogenase complex, PDC, via binding to the inner lipoyl domain L2 of the dihydrolipoyl acetyltransferase E2, PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal regulatory domain, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overall reaction of the pyruvate dehydrogenase complex, overview
-
-
?
additional information
?
-
-
model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms
-
-
?
additional information
?
-
-
fibrates induction of PDK4 might be coupled to an decrease in serum triglycerides and fatty acid levels which can cause protein degradation in muscles, PDK4 induction is increased in acute rhabdomyolysis
-
-
?
additional information
?
-
-
PDK4 is critically important in the starved state because it helps prevent hypoglycemia, the enzyme is part of the pyruvate dehydrogenase complex PDC, complex regulation and the molecular mechanisms
-
-
?
additional information
?
-
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
?
additional information
?
-
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
?
additional information
?
-
-
activity depends on the buffer system, the reduction status of the lipoyl groups and on the serine phosphorylation site of the E1 subunit of the pyruvate dehydrogenase complex used as substrate
-
-
?
additional information
?
-
-
performs autophosphorylation
-
-
?
additional information
?
-
-
binding of homodimers of PDK1 and PDK2, respectively and the heterodimer of PDK1+PDK2 to the pyruvate dehydrogenase complex via dihydrolipoyl transacetylase
-
-
?
additional information
?
-
binding of homodimers of PDK1 and PDK2, respectively and the heterodimer of PDK1+PDK2 to the pyruvate dehydrogenase complex via dihydrolipoyl transacetylase
-
-
?
additional information
?
-
-
PDK4 is critically important in the starved state because it helps prevent hypoglycemia, the enzyme is part of the pyruvate dehydrogenase complex PDC, complex regulation and the molecular mechanisms
-
-
?
additional information
?
-
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
?
additional information
?
-
-
PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate, regulation of the pyruvate dehydrogenase complex, PDK4 overexpression in association with type I diabetes
-
-
?
additional information
?
-
-
modelling of the molecular mechanisms of recognition of the inner lipoyl-bearing domain of dihydrolipoyl transacetylase and of the blood glucose-lowering compound AZD7545 by pyruvate dehydrogenase kinase 2, residues L140, K173, I176, E179 are essential for recognition, and to a lesser extent also D164, D172, and A174, PDHK2 residues forming interfaces with L2, i.e. K17, P22, F31, F44, R372, and K391, are also critical for the maintenance of enhanced PDHK2 activity in the E2-bound state
-
-
?
additional information
?
-
-
PD kinase isozymes PDK1, PDK2, PDK3 and PDK4, reduce the active form of pyruvate dehydrogenase complex, PDC, via binding to the inner lipoyl domain L2 of the dihydrolipoyl acetyltransferase E2, PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal regulatory domain, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overall reaction of the pyruvate dehydrogenase complex, overview
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ATP + Pda1p subunit
ADP + phosphorylated Pda1p subunit
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
ATP + SMAD1/5/8 protein
?
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
ATP + [pyruvate dehydrogenase A1 (acetyl-transferring)]
ADP + [pyruvate dehydrogenase A1 (acetyl-transferring)] phosphate
-
-
-
?
additional information
?
-
ATP + Pda1p subunit
ADP + phosphorylated Pda1p subunit
-
the enzyme is the kinase of the Saccharomyces cerevisiae pyruvate dehydrogenase complex, which negatively regulates the complex by reversible phosphorylation of its Pda1p subunit, overview
-
-
?
ATP + Pda1p subunit
ADP + phosphorylated Pda1p subunit
-
the enzyme is the kinase of the Saccharomyces cerevisiae pyruvate dehydrogenase complex, which negatively regulates the complex by reversible phosphorylation of its Pda1p subunit, overview
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
pyruvate dehydrogenase kinase is a negative regulator in the mitochondrial pyruvate dehydrogenase complex and plays a pivotal role in controlling TCA cycle and cell respiration
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
-
-
-
ir
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
a small pocket in the N-terminal region of PDHK2 is involved in enzyme regulation, the pocket is formed by residues L53, Y157, Y80, S83, I111, R112, H115, S153, R154, I157, R158, I161
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
PDHK plays a key role in controlling the balance between glucose and lipid oxidation according to substrate supply, PDHK inhibition leads to increased PDH activity increasing glucose oxidation
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
PDK is involved in fatty acid metabolism
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation of E2-bound E1
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
PDHK plays a key role in controlling the balance between glucose and lipid oxidation according to substrate supply, PDHK inhibition leads to increased PDH activity increasing glucose oxidation
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
phosphorylation by PDK inhibits the pyruvate dehydrogenase complex, PDK plays a regulatory role in glucose metabolism, PDK4 expression is regulated by hepatic nuclear factor 4 and peroxisome proliferator-activated receptor gamma coactivator, PGC-1alpha
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
-
enzyme has an important role in control of glucose homeostasis
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
-
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
-
PDHK4 inhibits the pyruvate dehydrogenase complex by phosphorylation during starvation, regulation mechanism, overview
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
phosphorylation at Ser292 by PDK1
-
-
r
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
-
-
-
?
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
beta-subunit harbors a regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
isozyme PDK3 has a putative regulatory role of the pyruvate dehydrogenase complex in sperm
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
involved in regulation of mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
enzyme regulation in the heart depends on thyroid hormone and lipid status
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
enzyme regulates glucose oxidation by pyruvate dehydrogenase complex, isozyme PDHK1 is of more potential importance in adult heart than the other isozymes
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
high-fat feeding increases the expression of isozyme PDK2, but not of PDK4, hyperthyroidism increases the expression of both isozymes, physiological implications
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
high-fat feeding increases the expression of isozyme PDK2, but not of PDK4, hyperthyroidism increases the expression of both isozymes, physiological implications
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
-
-
ir
additional information
?
-
-
PDK regulates the pyruvate dehydrogenase multienzyme complex activity
-
-
?
additional information
?
-
-
PDK4 is critically important in the starved state because it helps prevent hypoglycemia, the enzyme is part of the pyruvate dehydrogenase complex PDC, detailed overview and modeling of the complex regulation and the molecular mechanisms
-
-
?
additional information
?
-
-
peroxisome proliferator-activated receptors and insulin have regulatory functions in expression of isozymes PDK2 and PDK4, regulation mechanism
-
-
?
additional information
?
-
-
pyruvate dehydrogenase kinase is part of the pyruvate dehydrogenase complex, regulation and component interactions, PDK2 binds the inner lipoyl domain L2, preferably in dimeric form, overview
-
-
?
additional information
?
-
-
rapid upregulation of isozyme PDK4 in skeletal muscle after prolonged exercise, PDK activity is increased during prolonged exercise, physiologic/metabolic state, overview
-
-
?
additional information
?
-
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
?
additional information
?
-
-
the PDK/PDH pathway is reduced by 73% in non small cell lung carcinoma contributing to hypoxia-inducible factor-1 stability and aerobic glycolysis
-
-
?
additional information
?
-
-
a homodimer of pyruvate dehydrogenase kinase is an integral part of the pyruvate dehydrogenase complex, PDC, to which it is anchore primarily through the inner lipoyl-bearing domains L2 of transacetylase component, binding structure, catalytic cycle of PDHK and its translocation over the PDC surface is thought to be mediated by the symmetric and asymmetric modes, in which the PDHK dimer binds to two and one L2-domain(s), respectively, overview
-
-
?
additional information
?
-
-
hypoxia-inducible factor HIF-1, inducible e.g. by CoCl2, mediates the expression of PDK1, which inhibits the pyruvate dehydrogenase in the tricarboxylic cycle by phosphorylation, high PDK1 activity increases the ATP levels and prevents hypoxia-induced reactive oxygen species generation and apoptosis
-
-
?
additional information
?
-
-
PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate, regulation of the pyruvate dehydrogenase complex, PDK4 overexpression in association with type I diabetes
-
-
?
additional information
?
-
-
PDHK2 is required for binding to the inner lipoyl domain L2 of the dihydrolipoyl acetyltransferase of the pyruvate dehydrogenase complex
-
-
?
additional information
?
-
PDK isozymes are molecular switches that downregulate the pyruvate dehydrogenase complex PDC by reversible phosphorylation in mitochondria, L2 domain binding structure of isozyme PDK3, overview
-
-
?
additional information
?
-
-
PDK isozymes are molecular switches that downregulate the pyruvate dehydrogenase complex PDC by reversible phosphorylation in mitochondria, L2 domain binding structure of isozyme PDK3, overview
-
-
?
additional information
?
-
-
PDK4 expression is specifically regulated by retinoic acids, via retinoid receptors, and trichostatin A, an inhibitor of histone deacetylase
-
-
?
additional information
?
-
-
PDK4 is involved in metabolic changes after induction by high-fat/low carbohydrate diet, overview
-
-
?
additional information
?
-
-
phosphorylation of the pyruvate dehydrogenase complex PDC by the pyruvate dehydrogenase kinases PDK2 and PDK4 inhibits PDC activity, expression of the PDK genes is elevated in diabetes, leading to the decreased oxidation of pyruvate to acetyl-CoA, transcriptional regulation of the PDK4 gene by the estrogen-related receptors ERRalpha and ERRgamma, the ERRs are orphan nuclear receptors whose physiological roles include the induction of fatty acid oxidation in heart and muscle, overview
-
-
?
additional information
?
-
-
pyruvate dehydrogenase kinase isozymes are the molecular switch that down-regulates activity of the pyruvate dehydrogenase complex through reversible phosphorylation
-
-
?
additional information
?
-
-
model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms
-
-
?
additional information
?
-
-
fibrates induction of PDK4 might be coupled to an decrease in serum triglycerides and fatty acid levels which can cause protein degradation in muscles, PDK4 induction is increased in acute rhabdomyolysis
-
-
?
additional information
?
-
-
PDK4 is critically important in the starved state because it helps prevent hypoglycemia, the enzyme is part of the pyruvate dehydrogenase complex PDC, complex regulation and the molecular mechanisms
-
-
?
additional information
?
-
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
?
additional information
?
-
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
?
additional information
?
-
-
PDK4 is critically important in the starved state because it helps prevent hypoglycemia, the enzyme is part of the pyruvate dehydrogenase complex PDC, complex regulation and the molecular mechanisms
-
-
?
additional information
?
-
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
?
additional information
?
-
-
PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate, regulation of the pyruvate dehydrogenase complex, PDK4 overexpression in association with type I diabetes
-
-
?
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(2S)-2,6-diamino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)hexan-1-one
-
(2S)-2-amino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-hydroxypropan-1-one
-
(2S,3S)-2-amino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-hydroxybutan-1-one
-
(3R)-3-amino-4-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-4-oxobutanamide
-
(3S)-3-amino-4-(3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]azetidin-1-yl)-4-oxobutanamide
-
(3S)-3-amino-4-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-4-oxobutanamide
-
(3S)-3-amino-4-[(3R)-3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]pyrrolidin-1-yl]-4-oxobutanamide
-
(3S)-3-amino-4-[(3S)-3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]pyrrolidin-1-yl]-4-oxobutanamide
-
(3S)-3-amino-4-[4-[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]-1,4-diazepan-1-yl]-4-oxobutanamide
-
(3S)-3-amino-4-[4-[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl]-4-oxobutanamide
-
(4-benzylpiperidin-1-yl)[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazol-3-yl]methanone
-
(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)[(3R,5R)-3,4,5-trihydroxycyclohexyl]methanone
-
(4S)-4-amino-5-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-5-oxopentanamide
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(2-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3,4-dichlorophenyl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(4-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(pyridin-2-yl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(2-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3,4-dichlorophenyl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(4-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(pyridin-2-yl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)prop-2-en-1-one
-
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-phenylpiperazin-1-yl)prop-2-en-1-one
-
(R)-3,3,3-trifluoro-2-hydroxy-2-methylpropioamide
-
strong inhibition, isozymes PDK1 and PDK2, inhibition mechanism
(R)-4-(3-chloro-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido)phenylsulfonyl)-N,N-dimethylbenzamide
AZD7545
-
2-(2,6-dimethylphenoxy)-N-(1,3-dioxo-2-phenyl-2,3-dihydro-1H-isoindol-4-yl)acetamide
45.56% inhibition at 0.01 mM
2-(4-nitrophenyl)-2-oxoethyl 1H-indol-3-ylacetate
41.16% inhibition at 0.01 mM
2-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidine-1-carbonyl)benzoic acid
-
2-(5,6-dichloro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-nitrobenzoic acid
79.34% inhibition at 0.01 mM
2-([4-oxo-6-[(4-phenylpiperazin-1-yl)methyl]-4H-pyran-3-yl]oxy)-N-(propan-2-yl)acetamide
64.3% inhibition at 0.01 mM
2-chloro-4-formyl-6-methoxyphenyl 4-chloro-3-nitrobenzoate
41.26% inhibition at 0.01 mM
2-Chloroisohexanoate
-
weak
2-methyl-3-(2-[4-[4-(trifluoromethyl)benzoyl]piperazin-1-yl]ethoxy)-4H-pyran-4-one
-
-
2-methyl-3-[2-oxo-2-(4-phenylpiperazin-1-yl)ethoxy]-4H-pyran-4-one
-
-
2-methyl-3-[2-oxo-2-[4-(pyridin-2-yl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
-
-
2-methyl-3-[2-oxo-2-[4-(pyrimidin-2-yl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
-
-
2-methyl-3-[2-[4-(2-methylphenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
-
-
2-methyl-3-[2-[4-(2-nitrobenzoyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
-
-
2-methyl-3-[2-[4-(2-nitrophenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
-
-
2-methyl-3-[2-[4-(3-methylbenzoyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
-
-
2-methyl-3-[2-[4-(4-nitrophenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
-
-
2-methyl-3-[2-[4-(pyridin-2-ylcarbonyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
-
-
2-[(2,4-dihydroxyphenyl)sulfonyl]-2,3-dihydro-1H-isoindole-4,5-diol
-
2-[(6-[[4-(2-fluorophenyl)piperazin-1-yl]methyl]-4-oxo-4H-pyran-3-yl)oxy]-N-(propan-2-yl)acetamide
79.7% inhibition at 0.01 mM
2-[(6-[[4-(3-chlorophenyl)piperazin-1-yl]methyl]-4-oxo-4H-pyran-3-yl)oxy]-N-cyclopentylacetamide
47.5% inhibition at 0.01 mM
2-[5-[(2S)-1-benzylpiperidin-2-yl]-3-(oxan-4-yl)-1H-1,2,4-triazol-1-yl]ethan-1-ol
93.7% inhibition at 0.01 mM
3-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-oxopropanoic acid
-
3-[2-(4-(3-chlorophenyl)piperazin-1-yl)-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-(4-(3-fluorophenyl)piperazin-1-yl)-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-(4-benzoylpiperazin-1-yl)ethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(2-fluorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(2-fluorophenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(3,5-dimethoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(3,5-dimethylphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(3-methoxybenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(3-methoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(4-chlorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(4-fluorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(4-methoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(dichloroacetyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(diphenylmethyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
-
3-[2-[4-(furan-2-ylcarbonyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
-
4,5-dichloro-2-[[(2,4-dichlorophenyl)amino]carbonyl]benzoic acid
36.08% inhibition at 0.01 mM
4-(5-[[1-(2,3-dihydroxypropyl)piperidin-4-yl]amino]-1,3-dihydro-2H-isoindole-2-sulfonyl)benzene-1,3-diol
-
4-([(2R,5S)-2,5-dimethyl-4-[(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]piperazin-1-yl]carbonyl)benzonitrile
-
4-chloro-2-[[4-(propionyloxy)benzoyl]amino]enzoic acid
39.88% inhibition at 0.01 mM
4-[(5-amino-1,3-dihydro-2H-isoindol-2-yl)sulfonyl]benzene-1,3-diol
-
4-[(5-hydroxy-1,3-dihydro-2H-isoindol-2-yl)sulfonyl]benzene-1,3-diol
-
4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
inhibitor M77976 binds to the ATP-binding pocket of PDK4 and causes local conformational changes with complete disordering of the ATP lid. M77976 binding also leads to a large domain rearrangement that further expands the active-site cleft of PDK4 compared with the ADP- and AMPPNP-bound forms
4-[5-(cyclohexylamino)-1,3-dihydro-2H-isoindole-2-sulfonyl]benzene-1,3-diol
-
4-[5-[(1-benzylpiperidin-4-yl)amino]-1,3-dihydro-2H-isoindole-2-sulfonyl]benzene-1,3-diol
-
4-[[(3S)-3-(2-hydroxyethyl)-4-(3-methylbut-2-en-1-yl)piperazin-1-yl]methyl]-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
86.4% inhibition at 0.01 mM
4-[[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carbonyl]amino]-N-ethylpiperidine-1-carboxamide
-
4-[[5-(piperazin-1-yl)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
-
4-[[5-(piperidin-1-yl)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
-
4-[[5-(piperidin-4-ylamino)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
-
5-(3-bromophenyl)-4-(2-furoyl)-3-hydroxy-1-(5-isopropyl-1,3,4-thiadiazol-2-yl)-1,5-dihydro-2H-pyrrol-2-one
37.15% inhibition at 0.01 mM
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-(pyridin-4-yl)-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-(2-methylpropyl)piperidin-4-yl]-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-[(pyridin-4-yl)methyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-[4-[(morpholin-4-yl)methyl]phenyl]-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-[(2,4-dichlorophenyl)methyl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-[1-(cyclopropylmethyl)piperidin-4-yl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-[1-[(2,4-dichlorophenyl)methyl]piperidin-4-yl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-[4-(dimethylamino)phenyl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
5-bromo-2-([3-[(3-methylbenzoyl)amino]benzoyl]amino)benzoic acid
73.53% inhibition at 0.01 mM
5-[(1,3-benzodioxol-5-yloxy)methyl]-N-(imidazo[1,2-a]pyridin-3-ylmethyl)-N-methyl-1H-pyrazole-3-carboxamide
95.6% inhibition at 0.01 mM
6-(3,5-dichloro-4-hydroxybenzylidene)-5-imino-2-[(2-phenoxyethyl)thio]-5,6-dihydro-7H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one
42.87% inhibition at 0.01 mM
6-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-6-oxohexanoic acid
-
6-bromo-2-(2-methoxyphenyl)-4H-3,1-benzoxazin-4-one
45.07% inhibition at 0.01 mM
9-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-9-oxononanoic acid
-
adenosine 5'-[beta,gamma,imido]triphosphate
-
isozymes PDK1 and PDK2, inhibition mechanism
adenosine 5'-[beta,gamma-imido]triphosphate
-
-
ATP
-
above 0.5 mM, substrate inhibition, only in the presence of K+, Mg2+ does not protect
AZ12
-
i.e. N-[4-([ethylanilino]sulfonyl)2-methylphenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide, binding structure, requires K+ for inhibition
butyryl-CoA
-
at high concentrations
chymotrypsin
-
proteolysis of kinase alpha-, not beta-subunit, no inactivation by trypsin-mediated proteolysis of beta-subunit
-
Cl-
-
40% inhibition at 80 mM, K+-independent inhibition
Disulfides
-
thiols reverse
ethyl 5-benzyl-2-[([2-[(cyclohexylamino)carbonothioyl]hydrazine]carbonothioyl)amino]-3-thiophenecarboxylate
49.53% inhibition at 0.01 mM
H2O2
-
PDHK2 activity is inhibited by low levels of hydrogen peroxide generated by the respiratory chain via reversible oxidation of Cys45 and Cys392 on PDHK2
lactone derivative of dichloroacetophenone
-
isozymes PDK1 and PDK2, inhibition mechanism
menadione
-
PDHK2 activity is inhibited via reversible oxidation of Cys45 and Cys392 on PDHK2
methyl 4-[[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carbonyl]amino]piperidine-1-sulfinate
-
N-(1-acetylpiperidin-4-yl)-5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
N-(1-benzylpiperidin-4-yl)-5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
N-(3-methoxyphenyl)-2-[(phenylsulfonyl)amino]-5-pyrimidinecarboxamide
65.66% inhibition at 0.01 mM
N-(4-(2-chloro-5-methylpyrimidin-4-yl)-phenyl)-N-(4-((2,2-difluoroacetamido)methyl)benzyl)-2,4-dihydroxybenzamide
Ver-246608
-
N-butyl-3-(2-hydroxyphenyl)-N-(pyridin-4-ylmethyl)-1H-pyrazole-5-carboxamide
89.6% inhibition at 0.01 mM
N-methyl-2-([4-oxo-6-[(4-phenylpiperazin-1-yl)methyl]-4H-pyran-3-yl]oxy)acetamide
54.1% inhibition at 0.01 mM
N-[2-([[4-methyl-6-(piperidin-1-yl)pyrimidin-2-yl]methyl]amino)-2-oxoethyl]benzamide
20.1% inhibition at 0.01 mM
N1-(2-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]ethyl)-L-aspartamide
-
N1-(3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]propyl)-L-aspartamide
-
Na+
-
above 50 mM, alone and synergism with ADP
Pfz3
-
i.e. N-(2-aminoethyl)-2-(3-chloro-4-[(4-isopropylbenzyl)oxy]phenyl)acetamide, binding site structure, involves e.g. the R domain, allosteric inhibition mechanism, overview
PS10
2-[(2,4-dihydroxyphenyl)sulfonyl]-2,3-dihydro-1H-isoindole-4,6-diol
-
Pyruvamide
-
inhibition of isozymes PDK1, PDK2, and PDK4
Rapamycin
-
inhibits PDK2 and PDK4, has no effect on insulin-caused downregulation of the isozymes
SO42-
-
with the same effect as HPO42-
triterpenes
-
isozymes PDK1 and PDK2, inhibition mechanism
-
ADP
-
competitive to ATP
ADP
-
competitive to ATP; inhibition only in the presence of monovalent cations; Mg2+ does not protect
ADP
-
competitive to ATP; inhibition only in the presence of monovalent cations
ADP
-
inhibition only in the presence of monovalent cations
ADP
-
50-60% inhibition of isozyme PDK3, in presence of dihydrolipoyl transacetylase 70%
ADP
-
synergism with pyruvate
ADP
-
product inhibition, competitive to ATP, synergistic with pyruvate, PDK2, ADP, and pyruvate form a dead-end complex
ADP
-
binding site structure, involves Gly319 and Phe318, and K+ ions
ADP
-
product inhibition, L2 binding increases affinities for both ADP and ATP
ADP
-
product inhibition, synergistic with pyruvate
ADP
-
binding kinetics,ATP or ADP plus pyruvate at low concentration of about 0.1 mM cause PDHK2 dimer to associate to a tetramer. These changes make major contributions to synergistic inhibition of PDHK2 activity by ADP and pyruvate, overview
ADP
synergism with dichloroacetate
ADP
-
isozyme PDK3: synergistic with phosphate; isozyme PDK4: K+ and dichloroacetate increase the inhibitory effect; synergism with pyruvate
ADP
-
isozyme PDK2: synergistic with phosphate; synergism with pyruvate
ADP
-
competitive to ATP; inhibition only together with pyruvate, kinetics; synergism with pyruvate
ADP
competitive to ATP; isozyme PDK2, wild-type and mutants G284A and G319A
ADP
-
synergism with pyruvate
ADP
recombinant homodimers of PDK1 and PDK2 and heterodimers of PDK1 + PDK2, synergism with dichloroacetate; recombinant homodimers of PDK1 and PDK2 and heterodimers of PDK1 + PDK2, synergism with dichloroacetate
ADP
-
synergism with pyruvate
ADP
-
product inhibition, synergistic with pyruvate
AZD7545
-
noncompetitive to ATP
AZD7545
-
an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor
AZD7545
structural mechanisms for inhibition of pyruvate dehydrogenase kinase isozymes, binding structure analysis, overview, when the E2p/E3BP core is absent, AZD7545 stimulates scaffold-free basal PDK1 and PDK3 activities to 1.3fold and 10fold, respectively
AZD7545
-
noncompetitive to ATP, IC50 values for isozymes PDHK1, PDHK2, and PDHK4
AZD7545
-
compound AZD7545 disrupts the interactions between PDHK2 and L2 and thereby inhibits PDHK2 activity
AZD7545
-
an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor
CaCl2
-
no inhibition
compound K
-
an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor
compound K
-
noncompetitive to ATP, IC50 values for isozymes PDHK1, PDHK2, and PDHK4
compound K
-
an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor
Dichloroacetate
-
noncompetitive; pyruvate analog, synergism with ADP, K+ or phosphate, kinetics
Dichloroacetate
-
inhibition of isozyme PDK3 is independent of dihydrolipoyl transacetylase, while isozyme PDK2 is more sensitive to inhibition when bound to it
Dichloroacetate
-
binds at the pyruvate binding site, binding structure, involves e.g. Arg154
Dichloroacetate
-
R114, S83, I157 and, to some extent, H115 are essential for DCA binding by PDHK, Y80 and D117 are required for the communication between the dichloroacetate-binding site and active site of PDHK2, overview
Dichloroacetate
-
binding kinetics
Dichloroacetate
synergism with ADP, binding promotes conformational changes at the active-site cleft, structural mechanisms for inhibition of pyruvate dehydrogenase kinase isozymes, binding structure analysis, overview
Dichloroacetate
-
the PDK inhibitor restores pyruvate dehydrogenae activity and enhances glucose oxidation with beneficial molecular effects, i.e. downregulation of FOXO-1 and PDK4, and functional improvement,i.e. enhanced right ventricular function and exercise capacity
Dichloroacetate
-
isozyme PDK2: ADP and K+ increase the inhibitory effect; isozyme PDK4: ADP, K+ and Cl- increase the inhibitory effect
Dichloroacetate
-
potent and highly specific synthetic allosteric inhibitor mimicking pyruvate, inhibition mechanism
Dichloroacetate
recombinant homodimers of PDK1 and PDK2 and heterodimers of PDK1 + PDK2, synergism with dichloroacetate; recombinant homodimers of PDK1 and PDK2 and heterodimers of PDK1 + PDK2, synergism with dichloroacetate
Dichloroacetate
highly specific
Dichloroacetate
-
noncompetitive to ATP
Dichloroacetate
-
the PDK inhibitor restores pyruvate dehydrogenae activity and enhances glucose oxidation with beneficial molecular effects, i.e. downregulation of FOXO-1 and PDK4, and functional improvement,i.e. enhanced right ventricular function and exercise capacity
dichloroacetophenone
-
dichloroacetophenone
-
isozymes PDK1 and PDK2, inhibition mechanism
dihydrolipoic acid
-
inhibits the activity of PDK3 towards the reconstituted PD complex slightly, but the activity towards E1 alone completely, inhibition mechanism
dihydrolipoic acid
-
inhibits the activity of PDK1 towards the reconstituted PD complex, inhibition mechanism
DTNB
-
most potent at 0.001 mM
HPO42-
-
enhances inhibition by pyruvate or dichloroacetate
HPO42-
-
noncompetitive to ATP in the range of 1-10 mM; within physiological range, only in the presence of K+, not in its absence
Insulin
-
decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma
-
Insulin
-
blockage of the expression of isozyme PDK4 via insulin-activated pathway
-
K+
-
synergism with ADP
K+
-
pyruvate or dichloroacetate
Nov3r
-
i.e. (4-[(2,5)-dimethyl-4-(3,3,3-trifluoro-2-hydroxy-2-methyl-propanoyl)piperazinyl]carbonyl)benzonitrile, binding structure, requires K+ for inhibition
Nov3r
-
an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor, a mimic of the acetyl-dihydrolipoyl group, inhibits PDK2
Nov3r
-
an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor, a mimic of the acetyl-dihydrolipoyl group, inhibits PDK2
oximes of triterpenes
-
with 17beta hydroxyl and abietane derivatives, several, overview
-
oximes of triterpenes
-
with 17beta hydroxyl and abietane derivatives, several, overview
-
P53
-
negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2
P53
-
negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2
phosphate
-
enhances inhibition by pyruvate
phosphate
-
isozyme PDK2, synergistically with ADP and pyruvate
pyruvate
-
-
pyruvate
-
synergism with ADP
pyruvate
-
kinetics; noncompetitive to ATP; synergism with ADP; synergism with K+ or phosphate
pyruvate
-
synergism with ADP
pyruvate
-
very weak inhibition
pyruvate
-
product inhibition, synergistic with ADP, PDK2, ADP, and pyruvate form a dead-end complex
pyruvate
-
slight product inhibition, synergistic with ADP
pyruvate
-
binding kinetics,ATP or ADP plus pyruvate at low concentration of about 0.1 mM cause PDHK2 dimer to associate to a tetramer. These changes make major contributions to synergistic inhibition of PDHK2 activity by ADP and pyruvate, overview
pyruvate
-
Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase
pyruvate
-
inhibits at concentrations above 0.1 mM, activates below 0.05 mM; isozyme PDK2: ADP and K+ increase the inhibitory effect; isozyme PDK3; synergism with ADP
pyruvate
-
isozyme PDK2: synergistic with phosphate; isozyme PDK3; very weak inhibition
pyruvate
-
dead-end inhibitor; kinetics; noncompetitive to ATP; synergism with ADP
pyruvate
-
isozyme PDHK4 is less sensitive than PDHK1 and PDHK2
pyruvate
-
very weak inhibition
pyruvate
-
product inhibition, synergistic with ADP
R-lipoic acid
-
inhibits isozyme PDK3 activity in the reconstituted PD complex, but not towards E1 alone, inhibition mechanism
R-lipoic acid
-
inhibits isozymes PDK1, PDK2, and PDK4 activities in the reconstituted PD complex and towards E1 alone, inhibition mechanism, overview
radicicol
binding site structure, structural mechanisms for inhibition of pyruvate dehydrogenase kinase isozymes, binding structure analysis, overview
S-lipoic acid
-
inhibits isozyme PDK3 activity in the reconstituted PD complex, but not towards E1 alone, inhibition mechanism
S-lipoic acid
-
inhibits isozymes PDK1, PDK2, and PDK4 activities in the reconstituted PD complex and towards E1 alone, inhibition mechanism, overview
thiamine diphosphate
-
-
thiamine diphosphate
-
2-oxoisopentanoate protects, not pyruvate; non- or uncompetitively inhibition of K+-stimulated activity
thiamine diphosphate
-
kinetics; non- or uncompetitively inhibition of K+-stimulated activity
thiamine diphosphate
-
in the presence of pyruvate
Trypsin
-
-
additional information
-
no inhibition by 2-oxoglutarate; no inhibition by cAMP
-
additional information
-
no inhibition by cAMP; no inhibition by cGMP
-
additional information
-
no inhibition by cAMP; no inhibition by cGMP
-
additional information
-
no inhibition by cAMP; no inhibition by cGMP; not affected by calmodulin with or without Ca2+
-
additional information
-
no inhibition by succinyl-CoA, tiglyl-CoA, crotonyl-CoA, glutaryl-CoA, DL-3-hydroxy-3-methylglutaryl-CoA, acetylcarnitine or 3-hydroxybutyryl-CoA
-
additional information
-
-
-
additional information
-
carnitine, acetylcarnitine, malate, spermine, and calcium have no effect on isozyme PDK3 in presence of dihydrolipoyl transacetylase
-
additional information
-
-
-
additional information
-
-
-
additional information
-
insulin regulate the basal expression level of PDK4 by inhibiting the glucocorticoid-dependent stimulation of PDK4 expression via inactivation of FOXO proteins, FOXO proteins bind to the insulin response element which is required for the glucocorticoid response
-
additional information
-
effects of recombinant E2 component-derived deletion constructs on PDK activity, overview
-
additional information
-
insulin reverses the stimulation effect of reduced glucose levels increasing expression levels of PDK2 and PDK4, insulin alone decreases the enzyme expression levels below basal values, insulin effects on the enzyme are inhibited by phosphoatidyl 3-kinase inhibitors wortmannin and LY294002, i.e. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
-
additional information
-
pyruvamide is a poor inhibitor of PDK3
-
additional information
-
high-fat diet with unaltered n-3 fatty acid levels leads to increase in PDK activity and decrease in PDH activity, high-fat diet with elevated levels of n-3 fatty acids attenuates the increase in PDH kinase activity and decreases PDH activity, overview
-
additional information
-
PDK2 inhibition mechanism, overview
-
additional information
-
insulin downregulates expression of PDK4, but not of PDK2, after high-fat and control diets, but does not regulate the PDK4 protein
-
additional information
inhibition of FGFR1 by a small molecule inhibitor TKI258 results in decreased tyrosine phosphorylation levels of GST-PDHK1 and reduced PDHK1 activity
-
additional information
-
inhibition of FGFR1 by a small molecule inhibitor TKI258 results in decreased tyrosine phosphorylation levels of GST-PDHK1 and reduced PDHK1 activity
-
additional information
-
model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms; the effects of mono- and divalent ions vary greatly between the isozymes
-
additional information
-
isozyme PDK3 undergoes self-association in absence of dihydrolipoyl transacetylase domain L2 leading to a decrease in activity; starvation and diabetes reduce the expression of isozyme PDK2
-
additional information
-
isozyme-specific inhibition by AZD7545 analogues
-
additional information
-
PDK2 inhibition mechanism, overview
-
additional information
-
increase of ionic strength inhibits, changes of osmolarity of assay medium do not affect activity
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
acetoacetyl-CoA
-
slight activation
AZD7545
structural mechanisms for inhibition of pyruvate dehydrogenase kinase isozymes, binding structure analysis, overview, when the E2p/E3BP core is absent, AZD7545 stimulates scaffold-free basal PDK1 and PDK3 activities to 1.3fold and 10fold, respectively
benzoyl-CoA
-
slight activation
dibutyryl cAMP
-
in muscle, reversed by insulin
dihydrolipoyl transacetylase
-
fatty acids
-
leads to overexpression of isozyme PDK4 via mechanism involving peroxisome proliferator-activated receptor-alpha
inner lipoyl-bearing domain 2
-
i.e. L2, binding to the inner lipoyl domain L2 of E2 component of the PDC enzyme complex activates and regulates the enzyme by conformational changes and disrupting the ATP lid and eliminating product inhibition by ADP, mechanism, L2 binding strongly decreases PDHK2 affinity for ATP, strongest activation occurrs in presence of E1, E1-binding domain, and E2, overview
-
L-methylmalonyl-CoA
-
slight activation
L2 domain
-
inner lipoyl domain of the E2 component of PDC, activates PDK2
-
L2 domain of pyruvate dehydrogenase complex
-
binding to the inner lipoyl domains L2 of E2 component activate the enzyme by conformational changes and disrupting the ATP lid and eliminating product inhibition by ADP, binding structure, overview, L2 binding increases affinities for both ADP and ATP
-
lipoyl domain L2
-
L2 of the PDK3-containing pyruvate dehydrogenase complex induces a cross-tail conformation in PDK3, resulting in an opening of the active site cleft and the stimulation of kinase activity
-
Octanoate
-
in muscle, reversed by insulin
oleate
-
activates PDK2 and PDK4 nearly 2fold at 0.1 mM, not synergistic with palmitate, stimulation is completely inhibited by insulin at 0.001 mM
palmitate
-
activates PDK2 and PDK4 nearly 2fold at 0.1 mM, not synergistic with oleate, stimulation is completely inhibited by insulin at 0.001 mmM
peroxisome proliferator-activated receptor-alpha
-
involved in mechanism to enhance expression of isozyme PDK4, but not isozyme PDK2, during starvation
-
phosphate
-
isozyme PDK43, direct inhibition and elevation of the Km for ATP
propionyl-CoA
-
slight activation at low concentrations, synergism with NADH plus NAD+
Thyroid hormones
-
selective increase in amount of isozyme PDHK4 protein in both hyperthyroidism and high-fat feeding
-
2-oxoisopentanoate
-
-
2-oxoisopentanoate
-
only in the presence of K+ and thiamine diphosphate, kinetics
acetyl-CoA
kinase bound to transacetylase core
acetyl-CoA
synergism with NADH
acetyl-CoA
-
involved in the regulation of enzyme activity regulating pyruvate dehydrogenase complex
acetyl-CoA
-
high stimulation through acetylation of the transacetylase-catalyzing inner core portion of the dihydrolipoyl acetyltransferase
acetyl-CoA
-
synergism with NADH
acetyl-CoA
-
kinase bound to transacetylase core
acetyl-CoA
-
synergism with NADH
acetyl-CoA
-
domain-specific binding, isozymes PDK2 and PDK3
acetyl-CoA
-
synergism with NADH
acetyl-CoA
-
stimulation by acetyl-CoA requires both K+ and at least one anion, phosphate or chloride, mechanisms for stimulation of PDK2, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overview
acetyl-CoA
-
Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase
acetyl-CoA
-
activates the enzyme, especially isozyme PDK2
acetyl-CoA
-
domain-specific binding, isozymes PDK2 and PDK3
acetyl-CoA
-
isozyme PDK2: addition of K+ and Cl- required, phosphate increases the stimulating effect
acetyl-CoA
-
synergism with NADH
acetyl-CoA
-
involved in the regulation of enzyme activity regulating pyruvate dehydrogenase complex
acetyl-CoA
-
stimulation by acetyl-CoA requires both K+ and at least one anion, phosphate or chloride, mechanisms for stimulation of PDK2, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overview
dihydrolipoyl transacetylase
pyruvate dehydrogenase-complex transacetylase core
-
dihydrolipoyl transacetylase
-
-
-
dihydrolipoyl transacetylase
-
3-5fold stimulation
-
dihydrolipoyl transacetylase
-
involved in the regulation of enzyme activity regulating pyruvate dehydrogenase complex
-
dihydrolipoyl transacetylase
-
binding and activation mechanism
-
dihydrolipoyl transacetylase
-
pyruvate dehydrogenase-complex transacetylase core
-
dihydrolipoyl transacetylase
-
pyruvate dehydrogenase-complex transacetylase core
-
dihydrolipoyl transacetylase
-
degree of interaction and mechanism differ for the 4 different isozymes
-
dihydrolipoyl transacetylase
-
stimulation rates in different buffers, stimulating domains for the isozyme PDK2 and PDK3 differ, overview
-
dihydrolipoyl transacetylase
-
activation in presence of a binding protein, referred to as dihydrolipoamide dehydrogenase-binding protein
-
dihydrolipoyl transacetylase
-
activation depends on the buffer system, the isozyme and the reduction status of the lipoyl groups
-
dihydrolipoyl transacetylase
-
lipoylation is required for binding, structural mutants stimulate less
-
dihydrolipoyl transacetylase
-
dynamic, effector-modified interactions of the regulatory isozymes with the flexibly held outer domains of the core-forming dihydrolipoyl acetyl transferase component of pyruvate dehydrogenase complex to adapt the complex activity, regulatory mechanism
-
dihydrolipoyl transacetylase
-
domaine-specific binding, isozymes PDK2 and PDK3, the latter binding more tightly to the L2 domain
-
dihydrolipoyl transacetylase
-
degree of interaction and mechanism differ for the 4 different isozymes
-
dihydrolipoyl transacetylase
-
isozyme PDK2 can phosphorylate free pyruvate dehydrogenase complex but bound dihydrolipoyl transacetylase enhances the rate up to 5000fold
-
dihydrolipoyl transacetylase
-
acts as a direct allosteric agent in altering the regulatory kinase activity, serves as an anchoring scaffold
-
dihydrolipoyl transacetylase
-
binding and activation mechanism
-
dihydrolipoyl transacetylase
-
dynamic, effector-modified interactions of the regulatory isozymes with the flexibly held outer domains of the core-forming dihydrolipoyl acetyl transferase component of pyruvate dehydrogenase complex to adapt the complex activity, regulatory mechanism
-
dihydrolipoyl transacetylase
-
-
-
dihydrolipoyl transacetylase
-
requirement
-
dihydrolipoyl transacetylase
-
degree of interaction and mechanism differ for the 4 different isozymes
-
dihydrolipoyl transacetylase
-
isozyme PDK2, activation mechanism, binding structure
-
dihydrolipoyl transacetylase
-
activation in presence of a binding protein, referred to as dihydrolipoamide dehydrogenase-binding protein
-
dihydrolipoyl transacetylase
-
activation depends on the buffer system, the isozyme and the reduction status of the lipoyl groups
-
dihydrolipoyl transacetylase
-
dynamic, effector-modified interactions of the regulatory isozymes with the flexibly held outer domains of the core-forming dihydrolipoyl acetyl transferase component of pyruvate dehydrogenase complex to adapt the complex activity, regulatory mechanism
-
dihydrolipoyl transacetylase
-
rate-limiting in the holo-complex
-
glucocorticoids
-
regulate the basal expression level of PDK4, bind to a glucorticoid response element GRE located in the proximal promotor requiring binding of FOXO proteins, FOXO protein binding to the GRE can be inhibited by insulin, glucocorticoids act synergistically with retinoic acid
-
glucocorticoids
-
leads to overexpression of isozyme PDK4 via mechanism involving peroxisome proliferator-activated receptor-alpha
-
Lipid
-
selective increase in amount of isozyme PDHK4 protein in both hyperthyroidism and high-fat feeding
Lipid
-
enhance expression of hepatic isozyme PDK2 during high-fat feeding
Lipid
-
in muscle, reversed by insulin
NADH
kinase bound to transacetylase core
NADH
synergism with acetyl-CoA
NADH
-
involved in the regulation of enzyme activity regulating pyruvate dehydrogenase complex
NADH
-
activation, in the presence of NH4+
NADH
-
activation, in the presence of K+
NADH
-
kinase bound to transacetylase core
NADH
-
synergism with acetyl-CoA
NADH
-
domain-specific binding, isozymes PDK2 and PDK3
NADH
-
synergism with acetyl-CoA
NADH
-
stimulation by NADH requires both K+ and at least one anion, phosphate or chloride, mechanisms for stimulation of PDK2, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overview
NADH
-
Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase
NADH
-
activates the enzyme, especially isozyme PDK2
NADH
-
domain-specific binding, isozymes PDK2 and PDK3
NADH
-
isozyme PDK2: addition of K+ and Cl- required, phosphate increases the stimulating effect
NADH
-
involved in the regulation of enzyme activity regulating pyruvate dehydrogenase complex
NADH
-
stimulation by NADH requires both K+ and at least one anion, phosphate or chloride, mechanisms for stimulation of PDK2, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overview
pyruvate
-
-
pyruvate
-
at low concentration, with the thiamine diphosphate containing pyruvate dehydrogenase complex, stimulation mechanism
pyruvate
-
inhibits at concentrations above 0.1 mM, activates below 0.05 mM, dependent on thiamine diphosphate
WY-14,643
-
activator of peroxisome proliferator-activated receptor-alpha
WY-14,643
-
in liver, specifically increases PDK4 expression
WY-14,643
-
in gastrocnemius muscle, specifically increases PDK4 expression
additional information
-
agonist activation of peroxisome proliferator-activated receptors alpha and delta specifically upregulates PDK4 transcription, while activation of peroxisome proliferator-activated receptor gamma specifically downregulates PDK2 transcription, reduced glucose levels increase expression levels of PDK2 and PDK4, the stimulation effect is reversed by insulin, insulin alone decreases the enzyme expression levels below basal values
-
additional information
-
effects of recombinant E2 component-derived deletion constructs on PDK activity, overview
-
additional information
-
farnesoid X receptor agonists stimulate PDK4 expression in hepatocytes in vitro
-
additional information
-
fasting largely increases PDK4 expression, increases PDK3 expression, but effects PDK2 and PDK1 only slightly in skeletal muscle, overview, peroxisome proliferator-activated receptor-alpha PPAR-alpha protein and forkhead homologue FKHR in rhabdomyosarcoma are putative transcriptional activators of the enzyme
-
additional information
-
histone acetylation and transcription activation of gene PDK4 by retinoic acid and trichostatin A, retinoic acid acts synergistically with glucocorticoids, induction by dexamethasone can be inhibited by RU486
-
additional information
-
rapid upregulation of isozyme PDK4 in skeletal muscle after prolonged exercise, PDK activity is increased 2.5fold during 240 min of exercise
-
additional information
-
the enzyme is stimulated 3.45fold by NADH/NAD+ and/or acetyl-Co via reduction and reductive acetylation of the lipoyl moieties of pyruvate dehydrogenase complex component E2 dihydrolipoyl acetyltransferase requiring elevated levels of Cl- and K+, activation increases the kcat and Km for ATP
-
additional information
-
the enzyme is stimulated by reduction or reduction/acetylation of the lipoyl moieties of pyruvate dehydrogenase complex component E2
-
additional information
-
hypoxia-inducible factor HIF-1 induces PDK1 expression, PDK1 is a direct target gene of HIF-1
-
additional information
-
PDK4 expression is 2fold induced in high-fat/low carbohydrate diet and is blunted under basal and clamp conditions after high-fat diet, overview
-
additional information
-
PDK4 expression is induced by retinoic acids and trichostatin A
-
additional information
-
the peroxisome proliferator-activated receptor gamma coactivator, PGC-1gamma, as well as estrogen-related receptors ERRalpha and ERRgamma stimulate the expression of isozymes PDK2 and PDK4, the latter being inhibited by insulin, expression of the PDK genes is elevated in diabetes, leading to the decreased oxidation of pyruvate to acetyl-CoA, overview
-
additional information
tyrosine phosphorylation enhances PDHK1 kinase activity by promoting ATP and pyruvate dehydrogenase complex binding
-
additional information
-
tyrosine phosphorylation enhances PDHK1 kinase activity by promoting ATP and pyruvate dehydrogenase complex binding
-
additional information
-
model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms
-
additional information
-
starvation increases expression of isozyme PDK4
-
additional information
-
farnesoid X receptor agonist GW4064 stimulates PDK4 expression in liver in vivo
-
additional information
-
no effects on PDK4 expression level by dexamethasone
-
additional information
-
PDK4 mRNA is very rapidly induced by fibrates, e.g. bezafibrate, and statins, e.g. statin, pravastatin, or simvastatin, and anti-bacterial drugs, e.g. quinolon, ofloxacin, and norfloxacin, in a tissue-specific manner, overview
-
additional information
-
-
-
additional information
-
during hyperthyroidism, the expression of hepatic isozymes PDK2 and PDK4 is increased
-
additional information
-
starvation increases expression of isozyme PDK4
-
additional information
-
starvation increases expression of isozyme PDK4
-
additional information
-
glucocorticoids and farnesoid X receptor agonists, dexamethasone or WY14643, stimulate PDK4 expression in hepatoma cells in vitro
-
additional information
-
glucocorticoids and insulin regulate the basal expression level of PDK4, starvation and diabetes mellitus increase PDK4 expression in most tissues, no effects by dexamethasone
-
additional information
-
PDK4 expression is induced by hepatic nuclear factor 4, HNF4, determination of binding sites on the PDK4 promoter
-
additional information
-
the enzyme is stimulated by reduction or reduction/acetylation of the lipoyl moieties of pyruvate dehydrogenase complex component E2
-
additional information
-
E2-dependent PDHK2 activation, molecular modeling and mechanism
-
additional information
-
expression of isozymes PDK2 and PDK4 is induced by free fatty acids, overview
-
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0.00058
(2S)-2,6-diamino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)hexan-1-one
Homo sapiens
at pH 7.5 and 25°C
0.000068
(2S)-2-amino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-hydroxypropan-1-one
Homo sapiens
at pH 7.5 and 25°C
0.000091
(2S,3S)-2-amino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-hydroxybutan-1-one
Homo sapiens
at pH 7.5 and 25°C
0.000065
(3S)-3-amino-4-(3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]azetidin-1-yl)-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.000058
(3S)-3-amino-4-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.000221
(3S)-3-amino-4-[(3R)-3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]pyrrolidin-1-yl]-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.000156
(3S)-3-amino-4-[(3S)-3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]pyrrolidin-1-yl]-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.001514
(3S)-3-amino-4-[4-[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]-1,4-diazepan-1-yl]-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.000767
(3S)-3-amino-4-[4-[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl]-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.01
(4-benzylpiperidin-1-yl)[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazol-3-yl]methanone
Homo sapiens
IC50 above 0.01 mM, pH and temperature not specified in the publication
0.000432
(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)[(3R,5R)-3,4,5-trihydroxycyclohexyl]methanone
Homo sapiens
at pH 7.5 and 25°C
0.000072
(4S)-4-amino-5-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-5-oxopentanamide
Homo sapiens
at pH 7.5 and 25°C
0.000604
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(2-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.001417
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3,4-dichlorophenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.002949
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000776
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000952
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(4-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000878
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(pyridin-2-yl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000521
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000845
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(2-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.004306
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3,4-dichlorophenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.002369
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000491
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000557
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(4-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.00105
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(pyridin-2-yl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.00107
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.001916
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-phenylpiperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000565
2-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidine-1-carbonyl)benzoic acid
Homo sapiens
at pH 7.5 and 25°C
0.0051
2-methyl-3-(2-[4-[4-(trifluoromethyl)benzoyl]piperazin-1-yl]ethoxy)-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.0018
2-methyl-3-[2-oxo-2-(4-phenylpiperazin-1-yl)ethoxy]-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
2-methyl-3-[2-oxo-2-[4-(pyridin-2-yl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
2-methyl-3-[2-oxo-2-[4-(pyrimidin-2-yl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
2-methyl-3-[2-[4-(2-methylphenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.003
2-methyl-3-[2-[4-(2-nitrobenzoyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.0063
2-methyl-3-[2-[4-(2-nitrophenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
2-methyl-3-[2-[4-(3-methylbenzoyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.0008
2-methyl-3-[2-[4-(4-nitrophenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
2-methyl-3-[2-[4-(pyridin-2-ylcarbonyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.000456
2-[(2,4-dihydroxyphenyl)sulfonyl]-2,3-dihydro-1H-isoindole-4,5-diol
Homo sapiens
at pH 7.5 and 25°C
0.0059 - 0.0076
2-[5-[(2S)-1-benzylpiperidin-2-yl]-3-(oxan-4-yl)-1H-1,2,4-triazol-1-yl]ethan-1-ol
0.001657
3-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-oxopropanoic acid
Homo sapiens
at pH 7.5 and 25°C
0.0091
3-[2-(4-(3-chlorophenyl)piperazin-1-yl)-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.001
3-[2-(4-(3-fluorophenyl)piperazin-1-yl)-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
3-[2-(4-benzoylpiperazin-1-yl)ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.0059
3-[2-[4-(2-fluorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
3-[2-[4-(2-fluorophenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
3-[2-[4-(3,5-dimethoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.0081
3-[2-[4-(3,5-dimethylphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
3-[2-[4-(3-methoxybenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
3-[2-[4-(3-methoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.0039
3-[2-[4-(4-chlorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.0008
3-[2-[4-(4-fluorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.0014
3-[2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
3-[2-[4-(4-methoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
3-[2-[4-(dichloroacetyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
3-[2-[4-(diphenylmethyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.0016
3-[2-[4-(furan-2-ylcarbonyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.000154
4-(5-[[1-(2,3-dihydroxypropyl)piperidin-4-yl]amino]-1,3-dihydro-2H-isoindole-2-sulfonyl)benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.001177
4-[(5-amino-1,3-dihydro-2H-isoindol-2-yl)sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.00057
4-[(5-hydroxy-1,3-dihydro-2H-isoindol-2-yl)sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.648
4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
Homo sapiens
pH 8.0, temperature not specified in the publication
0.00196
4-[5-(cyclohexylamino)-1,3-dihydro-2H-isoindole-2-sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.000416
4-[5-[(1-benzylpiperidin-4-yl)amino]-1,3-dihydro-2H-isoindole-2-sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.00015
4-[[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carbonyl]amino]-N-ethylpiperidine-1-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.001346
4-[[5-(piperazin-1-yl)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.004371
4-[[5-(piperidin-1-yl)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.000195
4-[[5-(piperidin-4-ylamino)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.00058
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-(pyridin-4-yl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000068
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-(2-methylpropyl)piperidin-4-yl]-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000017
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000059
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-[(pyridin-4-yl)methyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00061
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00095
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-[4-[(morpholin-4-yl)methyl]phenyl]-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00061
5-(5-chloro-2,4-dihydroxyphenyl)-N-[(2,4-dichlorophenyl)methyl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000028
5-(5-chloro-2,4-dihydroxyphenyl)-N-[1-(cyclopropylmethyl)piperidin-4-yl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00016
5-(5-chloro-2,4-dihydroxyphenyl)-N-[1-[(2,4-dichlorophenyl)methyl]piperidin-4-yl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00038
5-(5-chloro-2,4-dihydroxyphenyl)-N-[4-(dimethylamino)phenyl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.0157 - 0.0178
5-[(1,3-benzodioxol-5-yloxy)methyl]-N-(imidazo[1,2-a]pyridin-3-ylmethyl)-N-methyl-1H-pyrazole-3-carboxamide
0.00161
6-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-6-oxohexanoic acid
Homo sapiens
at pH 7.5 and 25°C
0.000629
9-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-9-oxononanoic acid
Homo sapiens
at pH 7.5 and 25°C
0.0113
AUY922
Homo sapiens
pH and temperature not specified in the publication
0.013 - 108
Dichloroacetate
0.03559 - 0.04679
ethyl 5-benzyl-2-[([2-[(cyclohexylamino)carbonothioyl]hydrazine]carbonothioyl)amino]-3-thiophenecarboxylate
0.00013
methyl 4-[[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carbonyl]amino]piperidine-1-sulfinate
Homo sapiens
pH and temperature not specified in the publication
0.00021
N-(1-acetylpiperidin-4-yl)-5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000025
N-(1-benzylpiperidin-4-yl)-5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000357
N1-(2-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]ethyl)-L-aspartamide
Homo sapiens
at pH 7.5 and 25°C
0.000067
N1-(3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]propyl)-L-aspartamide
Homo sapiens
at pH 7.5 and 25°C
0.0059
2-[5-[(2S)-1-benzylpiperidin-2-yl]-3-(oxan-4-yl)-1H-1,2,4-triazol-1-yl]ethan-1-ol
Homo sapiens
enzyme from A-549 cells, pH and temperature not specified in the publication
0.0076
2-[5-[(2S)-1-benzylpiperidin-2-yl]-3-(oxan-4-yl)-1H-1,2,4-triazol-1-yl]ethan-1-ol
Homo sapiens
enzyme from NCI-H1650 cells, pH and temperature not specified in the publication
0.0157
5-[(1,3-benzodioxol-5-yloxy)methyl]-N-(imidazo[1,2-a]pyridin-3-ylmethyl)-N-methyl-1H-pyrazole-3-carboxamide
Homo sapiens
enzyme from NCI-H1650 cells, pH and temperature not specified in the publication
0.0178
5-[(1,3-benzodioxol-5-yloxy)methyl]-N-(imidazo[1,2-a]pyridin-3-ylmethyl)-N-methyl-1H-pyrazole-3-carboxamide
Homo sapiens
enzyme from A-549 cells, pH and temperature not specified in the publication
0.087
AZD7545
Homo sapiens
pH 7.5, 25°C, inhibition of isozyme PDK1
0.6
AZD7545
Homo sapiens
pH 7.5, 25°C, inhibition of isozyme PDK3
0.013
Dichloroacetate
Homo sapiens
-
recombinant isozyme PDHK2 mutant I157A
0.29
Dichloroacetate
Homo sapiens
-
wild-type enzyme, apparent IC50 for basal activity
0.48
Dichloroacetate
Homo sapiens
-
wild-type enzyme, apparent IC50 for E2p/E3BP-dependent activity
1.2
Dichloroacetate
Homo sapiens
-
recombinant isozyme PDHK2 mutant R112A
1.7
Dichloroacetate
Homo sapiens
-
recombinant isozyme PDHK2 mutant R154A
2
Dichloroacetate
Homo sapiens
-
recombinant isozyme PDHK2 mutant R158A
2.3
Dichloroacetate
Homo sapiens
-
recombinant wild-type isozyme PDHK2
2.7
Dichloroacetate
Homo sapiens
-
recombinant isozyme PDHK2 mutant I161A
3.04
Dichloroacetate
Homo sapiens
-
mutant Y145F, apparent IC50 for basal activity
3.24
Dichloroacetate
Homo sapiens
-
mutant Y145F, apparent IC50 for E2p/E3BP-dependent activity
8.4
Dichloroacetate
Homo sapiens
-
recombinant isozyme PDHK2 mutant H115A
17.1
Dichloroacetate
Homo sapiens
-
recombinant isozyme PDHK2 mutant L53A
17.9
Dichloroacetate
Homo sapiens
-
recombinant isozyme PDHK2 mutant I111A
35.3
Dichloroacetate
Homo sapiens
-
mutant D382A/W383A, apparent IC50 for E2p/E3BP-dependent activity
37.9
Dichloroacetate
Homo sapiens
-
mutant D382A/W383A, apparent IC50 for basal activity
86.3
Dichloroacetate
Homo sapiens
-
mutant Y145F/R149A, apparent IC50 for E2p/E3BP-dependent activity
98.7
Dichloroacetate
Homo sapiens
-
mutant R149A, apparent IC50 for basal activity
102
Dichloroacetate
Homo sapiens
-
mutant Y145F/R149A, apparent IC50 for basal activity
108
Dichloroacetate
Homo sapiens
-
mutant R149A, apparent IC50 for E2p/E3BP-dependent activity
0.03559
ethyl 5-benzyl-2-[([2-[(cyclohexylamino)carbonothioyl]hydrazine]carbonothioyl)amino]-3-thiophenecarboxylate
Homo sapiens
enzyme from MCF-7 cells, at pH 7.2 and 37°C
0.03796
ethyl 5-benzyl-2-[([2-[(cyclohexylamino)carbonothioyl]hydrazine]carbonothioyl)amino]-3-thiophenecarboxylate
Homo sapiens
enzyme from PaCa-2 cells, at pH 7.2 and 37°C
0.04364
ethyl 5-benzyl-2-[([2-[(cyclohexylamino)carbonothioyl]hydrazine]carbonothioyl)amino]-3-thiophenecarboxylate
Homo sapiens
enzyme from T-98G cells, at pH 7.2 and 37°C
0.04536
ethyl 5-benzyl-2-[([2-[(cyclohexylamino)carbonothioyl]hydrazine]carbonothioyl)amino]-3-thiophenecarboxylate
Homo sapiens
enzyme from HCT-116 cells, at pH 7.2 and 37°C
0.04679
ethyl 5-benzyl-2-[([2-[(cyclohexylamino)carbonothioyl]hydrazine]carbonothioyl)amino]-3-thiophenecarboxylate
Homo sapiens
enzyme from A-549 cells, at pH 7.2 and 37°C
0.23
radicicol
Homo sapiens
pH 7.5, 25°C, inhibition of isozyme PDK1
0.4
radicicol
Homo sapiens
pH 7.5, 25°C, inhibition of isozyme PDK3
1.079
radicicol
Homo sapiens
pH 8.0, temperature not specified in the publication
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malfunction
-
enzyme inhibition results in increased pyruvate dehydrogenase complex activity. Oxidation of Cys45 or Cys392 inhibits PDHK2 activity. Dimer formation is not essential for PDHK2 inactivation via Cys392 oxidation, although it may potentiate it
malfunction
expression of phosphorylation-deficient, catalytic hypomorph PDHK1 mutants in cancer cells leads to decreased cell proliferation under hypoxia and increased oxidative phosphorylation with enhanced mitochondrial utilization of pyruvate, and reduced tumor growth in xenograft nude mice. Cells expressing catalytically less active mPDHK1 mutants, including Y134F and Y239/240F, rely more on oxidative phosphorylation for ATP production and cell proliferation compared to cells with mPDHK1 wild-type
malfunction
-
FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension, overview. The bioenergetic impairment and right ventricular dysfunction can be reversed by dichloroacetate
malfunction
-
FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension, overview. The bioenergetic impairment and right ventricular dysfunction can be reversed by dichloroacetate
malfunction
-
knockdown of PDH kinase 1 does not affect basal insulin secretion but, remarkably, insulin secretion in response to 16.7 mM glucose increases more vigorously than in negative control cells. The metabolite profile of cells with PDH kinase 1 knockdown is significantly different from that of the control cells, expecially the tricarboxylic acid cycle intermediates malate, fumarate and 2-oxoglutarate, overview
malfunction
-
pyruvate dehydrogenase activity is 2.5fold higher at rest in PDK4 knockout mouse muscle compared to the wild-type, and about 2fold in activated muscle at low and high intensity contraction
malfunction
-
wild-type mouse primary cortical neurons treated with amyloid beta peptide or cortical tissue extracts from 12-month-old APPswe/PS1dE9 transgenic mice show decreased expression of lactate dehydrogenase A and PDK1 when compared with controls
malfunction
-
wild-type mouse primary cortical neurons treated with amyloid beta peptide or cortical tissue extracts from 12-month-old APPswe/PS1dE9 transgenic mice show decreased expression of lactate dehydrogenase A and PDK1 when compared with controls
malfunction
enzyme deletion leads to growth retardation, failure in perithecia and conidia production, and increase in pigment formation as well as enhanced sensitivity to osmotic stress and cell membrane-damaging agent. The deletion of the enzyme also prohibits the production of deoxynivalenol and pathogenicity of Fusarium graminearum
malfunction
enzyme inhibition ameliorates the calcification in phosphate-treated vascular smooth muscle cells and aortic rings
malfunction
-
enzyme-deficiency dramatically reduces the expression of genes related to fatty acid uptake, synthesis and gluconeogenesis
malfunction
enzyme-deficiency dramatically reduces the expression of genes related to fatty acid uptake, synthesis and gluconeogenesis. Enzyme deficiency ameliorates the hepatic steatosis significantly in nonalcoholic steatohepatitis mice
malfunction
-
in the presence of glucose, enzyme deletion results in reduced glucose utilization, which affects carbon catabolite repression and hydrolytic enzyme secretion, due to de-regulated glycolysis and tricarboxylic acid cycle enzyme activities
malfunction
-
inhibition of isoform PDK1 decreases cell proliferation and induces cell cycle arrest, cell apoptosis and oxidative damage. Isoform PDK1 inhibition in HepG2 and HepG3B cancer cells affects the level of mitochondrial quality control. Analysis of mitochondrial function reveals significantly increased mitochondrial reactive oxygen species and decreased membrane potential. Therefore, glucose metabolism reprogramming by PDK1 inhibition can induce mitochondrial quality control disorders to aggravate mitochondrial stress damage
malfunction
isoform PDK2 ablation or inhibition in mouse astrocytes attenuates diabetes-induced hypothalamic inflammation, lactate surge, increased food intake, and hyperglycemia in mice
malfunction
isoform PDK2 deletion or inhibition prevents polarization of macrophages to the M1 phenotype in response to inflammatory stimuli (lipopolysaccharide plus interferon gamma). Global isoform PDK2 deficiency in high fat diet-fed mice reduces insulin resistance and adipose tissue inflammation
malfunction
isoform PDK4 deletion or inhibition prevents polarization of macrophages to the M1 phenotype in response to inflammatory stimuli (lipopolysaccharide plus interferon gamma). Global isoform PDK4 deficiency in high fat diet-fed mice reduces insulin resistance and adipose tissue inflammation
malfunction
-
FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension, overview. The bioenergetic impairment and right ventricular dysfunction can be reversed by dichloroacetate
-
malfunction
-
enzyme deletion leads to growth retardation, failure in perithecia and conidia production, and increase in pigment formation as well as enhanced sensitivity to osmotic stress and cell membrane-damaging agent. The deletion of the enzyme also prohibits the production of deoxynivalenol and pathogenicity of Fusarium graminearum
-
metabolism
-
metabolic profiling and glucose-stimulated insulin secretion in pancreatic beta cells with and without knockdown of the enzyme, overview
metabolism
mitochondrial pyruvate dehydrogenase complex, a key multienzyme system catalyzing the irreversible conversion of pyruvate to acetyl-CoA and NADH with CO2 as a byproduct, is regulated through inactivation by pyruvate dehydrogenase kinase phosphorylation and reactivation by phospho-PDH phosphatase dephosphorylation
metabolism
-
p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2, which negatively regulates the pyruvate dehydrogenase complex. Decreased levels of Pdk2 and P-Pdc in turn promote conversion of pyruvate into acetyl-CoA instead of lactate
metabolism
-
p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2, which negatively regulates the pyruvate dehydrogenase complex. Decreased levels of Pdk2 and P-Pdc in turn promote conversion of pyruvate into acetyl-CoA instead of lactate
metabolism
-
PDHK2 is responsible for short-term metabolic responses
metabolism
the mitochondrial pyruvate dehydrogenase complex, PDC, activity is tightly regulated by four members of a family of pyruvate dehydrogenase kinase isoforms, PDK1-4, which phosphorylate and inactivate PDC
metabolism
-
the enzyme is important for glucose utilization positively regulates pyruvate dehydrogenase complex activity
physiological function
phosphorylation (activation) of pyruvate dehydrogenase
physiological function
regulation and controlling of the pyruvate dehydrogenase complex activity in skeletal muscles by phosphorylation
physiological function
-
the mitochondrial pyruvate dehydrogenase complex, PDC, is down-regulated by phosphorylation catalyzed by pyruvate dehydrogenase kinase isoforms
physiological function
-
expression of PDK4 is regulated by its regulatory transcription factor, FOXO1. FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4. Pyruvate dehydrogenase kinase is activated in right ventricular hypertrophy, causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores gluccoe oxidation
physiological function
-
expression of PDK4 is regulated by its regulatory transcription factor, FOXO1. FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4. Pyruvate dehydrogenase kinase is activated in right ventricular hypertrophy, causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores gluccoe oxidation
physiological function
-
PDK1 phosphorylates and inhibits pyruvate dehydrogenase, an enzyme responsible for the conversion of pyruvate to acetyl-CoA
physiological function
-
PDK1 phosphorylates and inhibits pyruvate dehydrogenase, an enzyme responsible for the conversion of pyruvate to acetyl-CoA
physiological function
-
PDK1 phosphorylates and inhibits pyruvate dehydrogenase, an enzyme responsible for the conversion of pyruvate to acetyl-CoA
physiological function
-
Pdk2 is seen as the key control point in conversion of pyruvate to acetyl-CoA reaction because it responds allosterically to rapid local changes in substrate and product: Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase
physiological function
-
Pdk2 is seen as the key control point in conversion of pyruvate to acetyl-CoA reaction because it responds allosterically to rapid local changes in substrate and product: Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase. P53-dependent apoptosis requires downregulation of Pdk2, early apoptotic events do not occur unless p53 can downregulate the transcription of Pdk2
physiological function
-
pyruvate dehydrogenase kinase 4 is one of four PDH kinases regulating the function of the pyruvate dehydrogenase complex, PDH. PDK4 is responsible for reducing PDH activity during low- to moderate-intensity muscle stimulation for contraction of the extensor digitorum muscle
physiological function
pyruvate dehydrogenase kinase is a negative regulator of the mitochondrial pyruvate dehydrogenase complex, which plays a key role in intermediary metabolism
physiological function
-
regulation of Pdk4 gene expression by the CCAAT/enhancer-binding protein beta, i.e. C/EBPbeta, which modulates the expression of multiple hepatic genes including those involved in metabolism, development, and inflammation. C/EBPbeta induces Pdk4 gene expression and decreases pyruvate dehydrogenase complex activity, and it participates in the T3 induction of the Cpt1a and Pdk4 genes, overview
physiological function
tyrosine phosphorylation activates PDHK1 to promote the Warburg effect and tumor growth in cancer cells. Oncogenic FGFR1 is localized in mitochondria in cancer cells, where it phosphorylates PDHK1
physiological function
isoform PDK2 up-regulation in the diabetic dorsal root ganglion plays a critical role in inducing peripheral as well as central sensitizations, eventually causing diabetic neuropathic pain
physiological function
isoform PDK4 up-regulation in the diabetic dorsal root ganglion plays a critical role in inducing peripheral as well as central sensitizations, eventually causing diabetic neuropathic pain
physiological function
the enzyme augments the osteogenic differentiation of vascular smooth muscle cells by phosphorylating SMAD1/5/8 via direct interaction, which enhances BMP2 signaling
physiological function
the enzyme is essential for the repression of pyruvate dehydrogenase activity and morphogenesis of Fusarium graminearum
physiological function
-
the enzyme regulates hepatitis C virus replication
physiological function
astrocytic isoform PDK2 regulates metabolic and inflammatory pathways that contribute to hypothalamic manifestations of diabetes
physiological function
enzyme isoform PDK2 is a metabolic checkpoint for polarization of macrophages to the M1 phenotype
physiological function
enzyme isoform PDK4 is a metabolic checkpoint for polarization of macrophages to the M1 phenotype
physiological function
isoform PDK3 plays important role in the glucose metabolism and is associated with cancer progression
physiological function
the enzyme dominates the pivotal switch from mitochondrial respiration to aerobic glycolysis by inactivating pyruvate dehydrogenase in cancer cells
physiological function
-
the enzyme potentially contributes to the hepatic steatosis in nonalcoholic steatohepatitis via regulating several signaling pathway
physiological function
the enzyme potentially contributes to the hepatic steatosis in nonalcoholic steatohepatitis via regulating several signaling pathway
physiological function
-
expression of PDK4 is regulated by its regulatory transcription factor, FOXO1. FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4. Pyruvate dehydrogenase kinase is activated in right ventricular hypertrophy, causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores gluccoe oxidation
-
physiological function
-
the enzyme is essential for the repression of pyruvate dehydrogenase activity and morphogenesis of Fusarium graminearum
-
additional information
ADP-bound PDK4 has a slightly wider active-site cleft and a more disordered ATP lid compared with AMPPNP-bound PDK4, binding structures of ADP and AMPPNP to isozyme PDK4, detailed overview. The width of the active-site cleft of PDK4 is determined by the location of the Tyr332 side chain
additional information
-
ADP-bound PDK4 has a slightly wider active-site cleft and a more disordered ATP lid compared with AMPPNP-bound PDK4, binding structures of ADP and AMPPNP to isozyme PDK4, detailed overview. The width of the active-site cleft of PDK4 is determined by the location of the Tyr332 side chain
additional information
-
overexpression of lactate dehydrogenase A or PDK1 in the B12 central nervous system cell line confers resistance to amyloid beta, H2O2, and staurosporine. Increased survival in cells overexpressing lactate dehydrogenase A or PDK1, associated with decreased mitochondrial membrane potential
additional information
-
overexpression of lactate dehydrogenase A or PDK1 in the B12 central nervous system cell line confers resistance to amyloid beta, H2O2, and staurosporine. Increased survival in cells overexpressing lactate dehydrogenase A or PDK1. Increased survival in cells overexpressing LDHA or PDK1 is associated with decreased mitochondrial membrane potential
additional information
three-dimensional structures of the two isozymes PDK3 and PDK4 by homology modeling based on the crystal structures of mammalian PDKs, overview. Important structural differences modify the accessibility of the nucleotide binding site in the two isozymes, molecular dynamics and sequence/structure comparisons
additional information
three-dimensional structures of the two isozymes PDK3 and PDK4 by homology modeling based on the crystal structures of mammalian PDKs, overview. Important structural differences modify the accessibility of the nucleotide binding site in the two isozymes, molecular dynamics and sequence/structure comparisons
additional information
-
three-dimensional structures of the two isozymes PDK3 and PDK4 by homology modeling based on the crystal structures of mammalian PDKs, overview. Important structural differences modify the accessibility of the nucleotide binding site in the two isozymes, molecular dynamics and sequence/structure comparisons
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E238A
site-directed mutagenesis, highly reduced activity compared to the wild-type PDK
E238H
site-directed mutagenesis, highly reduced activity compared to the wild-type PDK
E238Q
site-directed mutagenesis, highly reduced activity compared to the wild-type PDK
H121A
site-directed mutagenesis, 50% decreased trans- and autophosphorylation activity
H121Q
site-directed mutagenesis, 50% decreased trans- and autophosphorylation activity
H233A
site-directed mutagenesis, reduced activity compared to the wild-type PDK
K241A
site-directed mutagenesis, highly reduced activity compared to the wild-type PDK
L234A
site-directed mutagenesis, reduced activity compared to the wild-type PDK
L234H
site-directed mutagenesis, reduced activity compared to the wild-type PDK
D117A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
D164A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
D172A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
D382A/W383A
-
substitutions in the DW-motif
E162A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
E170A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is reduced compared to the wild-type isozyme PDK3
E179A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is reduced compared to the wild-type isozyme PDK3
F32A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
F35A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
F48A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
H115A
-
site-directed mutagenesis, the mutant enzyme shows reduced inhibition by dichloroacetate compared to the wild-type PDHK2
I111A
-
site-directed mutagenesis, the mutant enzyme shows reduced inhibition by dichloroacetate compared to the wild-type PDHK2
I157A
-
site-directed mutagenesis, the mutant enzyme shows increased inhibition by dichloroacetate compared to the wild-type PDHK2
I161A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
L140A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is reduced compared to the wild-type isozyme PDK3
L27A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
L53A
-
site-directed mutagenesis, the mutant enzyme shows reduced inhibition by dichloroacetate compared to the wild-type PDHK2
P142A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is unaltered compared to the wild-type isozyme PDK3
R112A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
R114A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
R149A
-
substitution of an interacting residue of the DW-motif, mutant shows drastic increase in apparent IC50 value for dichloroacetate, increased affinity for ADP and ATP
R154A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
R158A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
R196A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
S83A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
T175A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is unaltered compared to the wild-type isozyme PDK3
W383F
-
site-directed mutagenesis of isozyme PDHK2, the mutant shows unaltered catalytic activity compared to the wild-type isozyme PDHK2, but altered ligand binding and higher sensitivity to inhibition by pyruvate and ADP
Y145F
-
substitution of an interacting residue of the DW-motif, increased affinity for ADP and ATP
Y145F/R149A
-
mutant shows drastic increase in apparent IC50 value for dichloroacetate
Y80A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
C195A
-
site-directed mutagenesis
C212A
-
site-directed mutagenesis
C395A
-
site-directed mutagenesis
C45A
-
site-directed mutagenesis
D282A
isozyme PDK2, site-directed mutagenesis, mutation of conserved amino acid, no activity, not able to bind ATP but the protein substrate
E389A
-
site-directed mutagenesis, the mutant shows unaltered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
F168A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
F28A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
F31A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
F44A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
G284A
isozyme PDK2, site-directed mutagenesis, mutation of conserved amino acid, properties similar to wild-type
G286A
isozyme PDK2, site-directed mutagenesis, mutation of conserved amino acid, no activity, not able to bind ATP but the protein substrate
G319A
isozyme PDK2, site-directed mutagenesis, mutation of conserved amino acid, catalytically active, but very poor binding of ATP
I167A
-
site-directed mutagenesis, the mutant shows slightly altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
K17A
-
site-directed mutagenesis, the mutant shows slightly altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
K368A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
K391A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
L160A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
L23A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
L45A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
N247A
isozyme PDK2, site-directed mutagenesis, mutation of conserved amino acid, no activity, not able to bind ATP but the protein substrate
P22A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
Q47A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
R250A
catalytic activity is markedly reduced, Kd value for ATP is 32fold increased, resistant to the inhibitory effect of dichloroacetate, a synthetic analogue of pyruvate
R372A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
T302A
catalytic activity is considerably reduced, Kd value for ATP is 24fold increased, resistant to the inhibitory effect of dichloroacetate, a synthetic analogue of pyruvate
Y320F
catalytic activity is slightly reduced, Kd value for ATP is decreased to 68%, resistant to the inhibitory effect of dichloroacetate, a synthetic analogue of pyruvate
additional information
construction of transgenic plants with silenced PDHK via expression of an antisense construct driven by both constitutive and seed-specific promoters leading to increased respiration rate in leaves, seed oil content, and seed weight in both cases, mutant phenotypes, overview
additional information
-
construction of transgenic plants with silenced PDHK via expression of an antisense construct driven by both constitutive and seed-specific promoters leading to increased respiration rate in leaves, seed oil content, and seed weight in both cases, mutant phenotypes, overview
additional information
overexpression of BnPDK1 in transgenic Arabidopsis thaliana lines repress the pyruvate dehydrogenase complex activity, and results in the decrease of seed oil content and leaf photosynthesis
additional information
-
overexpression of BnPDK1 in transgenic Arabidopsis thaliana lines repress the pyruvate dehydrogenase complex activity, and results in the decrease of seed oil content and leaf photosynthesis
additional information
-
construction of truncated enzyme forms, the N-terminally truncated form, residues 284-402, is catalytically inactive, the C-terminally reduced form, residues 1-334, shows reduced activity
additional information
-
construction of several E2 component-derived domains, overview
additional information
-
overexpression of PDK1 increases the ATP levels and prevents hypoxia-induced reactive oxygen species generation and apoptosis, hypoxia-inducible factor HIF-1 knockout embryonic fibroblasts fail to activate PDK1 and undergo apoptosis with a high rise in reactive oxygen species, hypoxic P493-6 cells with reduced PDK1 levels show impaired growth
additional information
-
serial truncations of the isozyme PDK3 C-terminal tail region either impede or abolish the binding of wild-type L2 to the PDK3 mutants, resulting in the reduction or absence of L2-enhanced kinase activity, overview
additional information
RNAi-mediated stable knockdown of endogenous human PDHK1 (hPDHK1) and rescue expression of wild-type and corresponding Y134F and Y239/240F mutant FLAG-tagged mouse PDHK1s to different extents, overview
additional information
-
RNAi-mediated stable knockdown of endogenous human PDHK1 (hPDHK1) and rescue expression of wild-type and corresponding Y134F and Y239/240F mutant FLAG-tagged mouse PDHK1s to different extents, overview
additional information
-
enzyme-deficient PDHK4-/- mice show lower blood glucose levels and increased pyruvate dehydrogenase complex activity in kidney, gastrocnemius muscle, diaphragm and heart, but not in the liver, compared to the wild-type mice, the mutant mice accumulate less lactate and pyruvate because of a faster rate of pyruvate oxidation and a reduced rate of glycolysis, phenotype, overview, heterozygous mutant mice show about 50% reduced enzyme activity in skeletal muscle, genotype distribution, overview
additional information
-
construction of PDK4 gene promoter deletion and point mutants for functional analysis, overview
additional information
-
knockdown of C/EBPbeta with siRNA
additional information
-
PDH kinase 1 knockout with siRNA, siRNA transfection into 832/13 clonal beta-cells, transfectant metabolite profiling compared to control cells, overview
additional information
-
stable knockdown of PDK1 in B12 cells by transfection with HuSH 29-mer shRNA
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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.