Information on EC 1.2.4.1 - pyruvate dehydrogenase (acetyl-transferring)

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
1.2.4.1
-
RECOMMENDED NAME
GeneOntology No.
pyruvate dehydrogenase (acetyl-transferring)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
-
-
-
-
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
two-step reaction: thiamine diphosphate dependent decarboxylation of pyruvate to 2-hydroxyethylidene-thiamine diphosphate and subsequent reductive acetylation of lipoic acid residues bound to the dihydrolipoamide acetyltransferase, EC 2.3.1.12
-
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
overall reaction of pyruvate dehydrogenase complex: CH3-CO-CO2H + CoA-SH + NAD+ = CH3-CO-S-CoA + CO2 + NADH + H+, proposed mechanism
-
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
active site interactions, reaction mechanism
P0AFG8
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
catalytic site is formed by the conserved residues Tyr281 and Arg282
-
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
reaction mechanism, role of water molecules
P0AFG8
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
active center communication between the cofactors in the enzyme complex. Only one of the thiamine molecules bound to the two active sites is in a chemically activated state whereas the thiamin in the inactive states ionizes with a rate that is at least three orders of magnitude smaller. Model of an active site synchronization via a proton wire that keeps the two active sites in an alternating activation state
-
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
reaction with phosphonolactylthiamine diphosphate gives a covalently bound, pre-decarboxylation reaction intermediate analogue tightly held in the active site through hydrogen bonds with H407, Y599, and H640
-
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
substrate channelling in the multienzyme complex rests on the recognition of the lipoyl domain by enzyme. Cofactor thiamine diphosphate and substrate pyruvate have distinct effects on enzyme/lipoyl domain interaction. conformational freedom is allowed by the linker in the movement of the lipoyl domain between active sites
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
acetyl CoA biosynthesis
-
-
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
Citrate cycle (TCA cycle)
-
-
Glycolysis / Gluconeogenesis
-
-
Metabolic pathways
-
-
Microbial metabolism in diverse environments
-
-
NIL
-
-
oxidative decarboxylation of pyruvate
-
-
pyruvate decarboxylation to acetyl CoA
-
-
Pyruvate metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
pyruvate:[dihydrolipoyllysine-residue acetyltransferase]-lipoyllysine 2-oxidoreductase (decarboxylating, acceptor-acetylating)
Contains thiamine diphosphate. It is a component (in multiple copies) of the multienzyme pyruvate dehydrogenase complex in which it is bound to a core of molecules of EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase, which also binds multiple copies of EC 1.8.1.4, dihydrolipoyl dehydrogenase. It does not act on free lipoamide or lipoyllysine, but only on the lipoyllysine residue in EC 2.3.1.12.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dehydrogenase, pyruvate
-
-
-
-
MtPDC
-
-
-
-
PDH
-
-
-
-
pyruvate decarboxylase
-
-
-
-
pyruvate dehydrogenase
-
-
-
-
pyruvate dehydrogenase complex
-
-
-
-
pyruvic acid dehydrogenase
-
-
-
-
pyruvic dehydrogenase
-
-
-
-
VEG220
-
-
-
-
Vegetative protein 220
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9014-20-4
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain ST
-
-
Manually annotated by BRENDA team
Aeromonas caviae ST
strain ST
-
-
Manually annotated by BRENDA team
microsporidia, uncertain whether pyruvate dehydrogenase is used in acetyl-CoA synthesis and whether the entire pyruvate dehydrogenase complex is present in microsporidia
-
-
Manually annotated by BRENDA team
E1alpha component of the pyruvate dehydrogenase multienzyme complex PDH
-
-
Manually annotated by BRENDA team
sugar beet, cv. TK81-O, type 2 variant of the E1alpha subunit
-
-
Manually annotated by BRENDA team
calf
-
-
Manually annotated by BRENDA team
E1 component of the pyruvate dehydrogenase multienzyme complex
-
-
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
pyruvate dehydrogenase complex
-
-
Manually annotated by BRENDA team
var. botrytis
-
-
Manually annotated by BRENDA team
var. italica, cauliflower, broccoli
-
-
Manually annotated by BRENDA team
analysis of enzyme phylogeny
SwissProt
Manually annotated by BRENDA team
fragment; strain 501R3
UniProt
Manually annotated by BRENDA team
Enterobacter cloacae 501R3
fragment; strain 501R3
UniProt
Manually annotated by BRENDA team
enzyme E1 is a component of the pyruvate dehydrogenase multienzyme complex PDHc
Uniprot
Manually annotated by BRENDA team
pyruvate dehydrogenase multienzyme complex component E1
Uniprot
Manually annotated by BRENDA team
strain K12
-
-
Manually annotated by BRENDA team
Escherichia coli K12
strain K12
-
-
Manually annotated by BRENDA team
subspecies Fundulus heteroclitus heteroclitus
-
-
Manually annotated by BRENDA team
enzyme is a component of the pyruvate dehydrogenase multienzyme complex
-
-
Manually annotated by BRENDA team
Hansenula miso
-
-
-
Manually annotated by BRENDA team
Hansenula sp.
-
-
-
Manually annotated by BRENDA team
comparison of recombinant somatic cell-specific isoform PDH1 and testis-specific isoform PDH2
-
-
Manually annotated by BRENDA team
hyperdiploid strain of Ehrlich-Lettre ascites carcinoma cells
-
-
Manually annotated by BRENDA team
Pigeon
-
-
-
Manually annotated by BRENDA team
organism contains only one single enzyme complex
-
-
Manually annotated by BRENDA team
enzyme is in complex with alpha-ketoglutarate dehydrogenase
-
-
Manually annotated by BRENDA team
var. N5
-
-
Manually annotated by BRENDA team
strain BY4741
-
-
Manually annotated by BRENDA team
regulatory role of pirin in the process of pyruvate catabolism through interaction with enzyme and inhibition of pyruvate dehydrogenase complex
-
-
Manually annotated by BRENDA team
cv. romano
Uniprot
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
expression in Lactococcus lactis
-
-
Manually annotated by BRENDA team
recombinant expression in Haloferax volcanii
-
-
Manually annotated by BRENDA team
Zymomonas mobilis ZM4
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
deletion of the E1a or E3 subunit genes of Plasmodium yoelii PDH causes no defect in blood stage development, mosquito stage development or early liver stage development. However, the gene deletions completely block the ability of the e1alpha- and e3-deficient parasites to form exo-erythrocytic merozoites during late liver stage development, thus preventing the initiation of a blood stage infection
physiological function
-
Plasmodium pyruvate dehydrogenase activity is only essential for the parasites progression from liver infection to blood infection. The sole role of PDH is to provide acetyl-CoA for FAS II. PDH subunits E1a and E3 subunits are not essential for either blood stage or mosquito stage development but are essential for late liver stage development
physiological function
-
pyruvate dehydrogenase is the rate-limiting enzyme coupling cytosolic glycolysis to mitochondrial citric acid cycle, and plays a critical role in maintaining homeostasis of brain glucose metabolism
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-hydroxyethylidene-thiamine diphosphate + 2,6-dichlorophenolindophenol
S-acetyldihydrolipoamide + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
?
2-keto-4-methylhexanoic acid + CoA + NAD+
3-methylpentanoyl-CoA + CO2 + NADH
show the reaction diagram
-
no substrate for wild-type, but for mutants I472A, I476F
-
-
?
2-ketobutanoate + CoA + NAD+
propanoyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
2-ketohexanoate + CoA + NAD+
pentanoyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
2-ketopentanoate + CoA + NAD+
butanoyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
acetaldehyde + benzaldehyde
(R)-phenylacetylcarbinol
show the reaction diagram
-
-
-
-
-
acetaldehyde + benzaldehyde
(R)-phenylacetylcarbinol
show the reaction diagram
-
-
-
-
-
acetaldehyde + benzaldehyde
(R)-phenylacetylcarbinol
show the reaction diagram
-
-
-
-
-
acetaldehyde + benzaldehyde
(R)-phenylacetylcarbinol
show the reaction diagram
-
-
-
-
-
acetaldehyde + benzaldehyde
(R)-phenylacetylcarbinol
show the reaction diagram
-
-
-
-
-
acetaldehyde + benzaldehyde
(R)-phenylacetylcarbinol
show the reaction diagram
-
-
-
-
-
acetaldehyde + benzaldehyde
(R)-phenylacetylcarbinol
show the reaction diagram
-
-
-
-
?
alpha-ketobutyrate + Fe(CN)63- + H2O
hydroxyacetate + CO2 + Fe(CN)64-
show the reaction diagram
-
-
-
?
alpha-ketobutyrate + lipoamide
S-propionyldihydrolipoamide + CO2
show the reaction diagram
-
-
-
?
pyruvate + 2,6-dichlorophenolindophenol
CO2 + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
?
pyruvate + acetylphosphinate + NAD+
(R)-acetoin + ? + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + acetylphosphinate + NAD+
(S)-acetoin + ? + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + ?
show the reaction diagram
-
artifical electron acceptor
-
-
ir
pyruvate + CoA + 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + ?
show the reaction diagram
-
artificial electron acceptor
-
-
?
pyruvate + CoA + 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
P0AFG8
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
P0AFG8
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
-
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
-
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
Q8NNF6
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
A2TC23
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
P08559
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
Q1KSF0
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
P0AFG8
enzyme E1 is a component of the pyruvate dehydrogenase multienzyme complex PDHc, and catalyzes the first step of the multistep process
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
enzyme is the E1alpha component of the pyruvate dehydrogenase multienzyme complex, regulation via reversible phosphorylation, age-related in crease in enzyme E1alpha activity due to age-related decline in pyruvate dehydrogenase kinase PDK-4, overview
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
first step of the overall reaction of the pyruvate dehydrogenase complex
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
P0AFG8
reaction of the citric acid or Krebs cycle
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
Zymomonas mobilis ZM4
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
Enterobacter cloacae 501R3
A2TC23
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
Aeromonas caviae ST
-
-
-
-
?
pyruvate + E2p lipoyl domain
acetylated E2p lipoyl domain + CO2
show the reaction diagram
-
-
-
-
?
pyruvate + Fe(CN)63- + H2O
CO2 + Fe(CN)64-
show the reaction diagram
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
-
-
ir
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
-
-
-
-
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
Q1KSF0
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
specific for
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
Hansenula miso
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
-
-
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
low reactivity with 2-ketovalerate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
Hansenula miso
-
low reactivity with 2-ketovalerate
-
-
-
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
low reactivity with 2-ketoisovalerate, low reactivity with 2-ketoisocaproate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
Hansenula sp.
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
Hansenula miso
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
-
-
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
-
-
-
?
pyruvate + pyruvate dehydrogenase complex subunit E2p
?
show the reaction diagram
-
-
-
-
?
pyruvate + [dihydrolipoyllysine-residue acetyltransferase]-lipoyllysine
[dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
-
-
-
-
-
benzoylformate + CoA + NAD+
benzoyl-CoA + CO2 + NADH
show the reaction diagram
-
no substrate for wild-type, but for mutants I472A, I476F
-
-
?
additional information
?
-
-
conjugates of indole-3-acetic acid with amino acids act as hormones and e.g. inhibit root elongation, the sensitivity of the mutant iar4-1 plant against these conjugates and plant hormones is reduced compared to the wild-type, overview
-
-
-
additional information
?
-
-
determination of free short-chain CoA esters in rat heart
-
-
-
additional information
?
-
-
E1 is bound to E2, both components of the pyruvate dehydrogenase multienzyme complex PDC, via the E1-binding B domain of E2, enzyme component organization in the pyruvate dehydrogenase multienzyme complex, regulatory role, overview
-
-
-
additional information
?
-
-
enzyme is essential for the tricatrboxylic cycle
-
-
-
additional information
?
-
-
overall reaction of the multienzyme complex, overview
-
-
-
additional information
?
-
-
pyruvate-supported mitochondrial respiration state 3
-
-
-
additional information
?
-
-
regulation of pyruvate dehydrogenase complex activity and citric acid cycle intermediates during high cardiac power generation, inhibition of fatty acid oxidation has a regulatory function, overview
-
-
-
additional information
?
-
-
N-terminal residues 1-45 of the pyruvate dehydrogenase complex E1 subunit interact with the E2 subunit and are required for activity of the complex but not for reductive acetylation of the E2 subunit
-
-
-
additional information
?
-
P0AFG8
reactions performed by the whole enzyme complex, overview
-
-
-
additional information
?
-
-
regulatory role of pirin in the process of pyruvate catabolism through interaction with enzyme and inhibition of pyruvate dehydrogenase complex
-
-
-
additional information
?
-
-
binds to the di-domain (lipoyl domain + linker + peripheral subunit binding domain) of the dihydrolipoyl acetyltransferase (E2) component for acetylation
-
-
-
additional information
?
-
-
in vivo there are 20-30 E1 molecules bound to each core of the mammalian PDC, the small binding domain of E2 in humans binds only to E1
-
-
-
additional information
?
-
-
the PDH complex irreversibly decarboxylates pyruvate to acetylCoA (PDH activity) in a reaction that involves the participation of the three enzymes forming the PDH complex: AceE (pyruvate decarboxylase), AceF (dihydrolipoil acetyltransferase) and Lpd (dihydrolipoil dehydrogenase)
-
-
-
additional information
?
-
-
the pyruvate dehydrogenase complex consists of multiple copies of several components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), dihydrolipoamide dehydrogenase (E3), E3-binding protein (BP), and specific kinases and phosphatases
-
-
-
additional information
?
-
-
the PDH complex irreversibly decarboxylates pyruvate to acetylCoA (PDH activity) in a reaction that involves the participation of the three enzymes forming the PDH complex: AceE (pyruvate decarboxylase), AceF (dihydrolipoil acetyltransferase) and Lpd (dihydrolipoil dehydrogenase)
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
P0AFG8
enzyme E1 is a component of the pyruvate dehydrogenase multienzyme complex PDHc, and catalyzes the first step of the multistep process
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
enzyme is the E1alpha component of the pyruvate dehydrogenase multienzyme complex, regulation via reversible phosphorylation, age-related in crease in enzyme E1alpha activity due to age-related decline in pyruvate dehydrogenase kinase PDK-4, overview
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
-
first step of the overall reaction of the pyruvate dehydrogenase complex
-
-
ir
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
P0AFG8
reaction of the citric acid or Krebs cycle
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
Zymomonas mobilis ZM4
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
show the reaction diagram
Aeromonas caviae ST
-
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
-
-
ir
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
specific for
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
Hansenula miso
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
-
-
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
low reactivity with 2-ketovalerate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
Hansenula miso
-
low reactivity with 2-ketovalerate
-
-
-
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
low reactivity with 2-ketoisovalerate, low reactivity with 2-ketoisocaproate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
Hansenula sp.
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
show the reaction diagram
Hansenula miso
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
-
-
pyruvate + [dihydrolipoyllysine-residue acetyltransferase]-lipoyllysine
[dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
show the reaction diagram
-
-
-
-
-
additional information
?
-
-
conjugates of indole-3-acetic acid with amino acids act as hormones and e.g. inhibit root elongation, the sensitivity of the mutant iar4-1 plant against these conjugates and plant hormones is reduced compared to the wild-type, overview
-
-
-
additional information
?
-
-
determination of free short-chain CoA esters in rat heart
-
-
-
additional information
?
-
-
E1 is bound to E2, both components of the pyruvate dehydrogenase multienzyme complex PDC, via the E1-binding B domain of E2, enzyme component organization in the pyruvate dehydrogenase multienzyme complex, regulatory role, overview
-
-
-
additional information
?
-
-
enzyme is essential for the tricatrboxylic cycle
-
-
-
additional information
?
-
-
overall reaction of the multienzyme complex, overview
-
-
-
additional information
?
-
-
pyruvate-supported mitochondrial respiration state 3
-
-
-
additional information
?
-
-
regulation of pyruvate dehydrogenase complex activity and citric acid cycle intermediates during high cardiac power generation, inhibition of fatty acid oxidation has a regulatory function, overview
-
-
-
additional information
?
-
-
regulatory role of pirin in the process of pyruvate catabolism through interaction with enzyme and inhibition of pyruvate dehydrogenase complex
-
-
-
additional information
?
-
-
the PDH complex irreversibly decarboxylates pyruvate to acetylCoA (PDH activity) in a reaction that involves the participation of the three enzymes forming the PDH complex: AceE (pyruvate decarboxylase), AceF (dihydrolipoil acetyltransferase) and Lpd (dihydrolipoil dehydrogenase)
-
-
-
additional information
?
-
-
the pyruvate dehydrogenase complex consists of multiple copies of several components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), dihydrolipoamide dehydrogenase (E3), E3-binding protein (BP), and specific kinases and phosphatases
-
-
-
additional information
?
-
-
the PDH complex irreversibly decarboxylates pyruvate to acetylCoA (PDH activity) in a reaction that involves the participation of the three enzymes forming the PDH complex: AceE (pyruvate decarboxylase), AceF (dihydrolipoil acetyltransferase) and Lpd (dihydrolipoil dehydrogenase)
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
-
-
NAD+
-
-
NAD+
Q1KSF0
-
thiamine diphosphate
Pigeon
-
two binding sites
thiamine diphosphate
Hansenula sp.
-
-
thiamine diphosphate
Pigeon
-
-
thiamine diphosphate
-
-
thiamine diphosphate
-
-
thiamine diphosphate
-
-
thiamine diphosphate
-
-
thiamine diphosphate
-
-
thiamine diphosphate
-
-
thiamine diphosphate
Hansenula miso
-
-
thiamine diphosphate
-
-
thiamine diphosphate
P0AFG8
dependent on, 2 bound in the V-conformation in clefts between the 2 subunits, completely buried in the structure, binding structure
thiamine diphosphate
P0AFG8
dependent on, binding structure and determinants, V conformation, K392 is important
thiamine diphosphate
-
dependent on, binding site
thiamine diphosphate
-
-
thiamine diphosphate
-
-
thiamine diphosphate
-
KD value 0.00047 mM
thiamine diphosphate
-
Km value 0.0034 mM for overall reaction
thiamine diphosphate
-
dependent
thiamine diphosphate
-
dependent
thiamine diphosphate
Q1KSF0
-
thiamine diphosphate
-
-
thiamine diphosphate
-
dependent
thiamine diphosphate
A2TC23
-
thiamine diphosphate
-
-
thiamine diphosphate
-
dependent on
additional information
-
CoA and NAD+ required by pyruvate dehydrogenase complex
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
-
Ca2+
-
can replace Mg2+
Ca2+
-
can replace Mg2+
Ca2+
-
can replace Mg2+
Ca2+
-
0.36 mM, 5fold activation; can replace Mg2+
Ca2+
-
activates mammalian pyruvate dehydrogenase phosphatase
Mg2+
-
absolute requirement
Mg2+
Hansenula sp.
-
-
Mg2+
-
0.36 mM, 5fold activation
Mg2+
-
no requirement
Mg2+
-
required
Mg2+
-
activates
Mg2+
-
activates mammalian pyruvate dehydrogenase phosphatase
Mn2+
-
can replace Mg2+
Mn2+
-
can replace Mg2+
Mn2+
-
can replace Mg2+
Ni2+
-
can replace Mg2+
Mn2+
-
0.11 mM, 2fold activation; can replace Mg2+
additional information
-
no activation by other divalent cations, except Mg2+, Mn2+, Ca2+, Ni2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2-chlorophenyl)(dimethoxyphosphoryl)methyl [3-(trifluoromethyl)phenoxy]acetate
-
-
(3,4-dichlorophenyl)(dimethoxyphosphoryl)methyl [3-(trifluoromethyl)phenoxy]acetate
-
-
(3-chlorophenyl)(dimethoxyphosphoryl)methyl [3-(trifluoromethyl)phenoxy]acetate
-
-
(4-chlorophenyl)(dimethoxyphosphoryl)methyl [3-(trifluoromethyl)phenoxy]acetate
-
-
(dimethoxyphosphoryl)(4-methylphenyl)methyl [3-(trifluoromethyl)phenoxy]acetate
-
-
(dimethoxyphosphoryl)(phenyl)methyl (2,3-dichlorophenoxy)acetate
-
-
(dimethoxyphosphoryl)(phenyl)methyl (2,6-dichlorophenoxy)acetate
-
-
(dimethoxyphosphoryl)(phenyl)methyl (2-chloro-5-methylphenoxy)acetate
-
-
(dimethoxyphosphoryl)(phenyl)methyl (3-fluorophenoxy)acetate
-
-
(dimethoxyphosphoryl)(phenyl)methyl (4-chloro-2-methylphenoxy)acetate
-
-
(dimethoxyphosphoryl)(phenyl)methyl (4-chloro-3-methylphenoxy)acetate
-
-
(dimethoxyphosphoryl)(phenyl)methyl (4-chlorophenoxy)acetate
-
-
(dimethoxyphosphoryl)(phenyl)methyl (4-fluorophenoxy)acetate
-
-
1-(dimethoxyphosphoryl)ethyl (2,3-dichlorophenoxy)acetate
-
-
1-(dimethoxyphosphoryl)ethyl (2,6-dichlorophenoxy)acetate
-
-
1-(dimethoxyphosphoryl)ethyl (2-chloro-5-methylphenoxy)acetate
-
-
1-(dimethoxyphosphoryl)ethyl (3-fluorophenoxy)acetate
-
-
1-(dimethoxyphosphoryl)ethyl (4-chloro-2-methylphenoxy)acetate
-
-
1-(dimethoxyphosphoryl)ethyl (4-chloro-3-methylphenoxy)acetate
-
-
1-(dimethoxyphosphoryl)ethyl (4-chlorophenoxy)acetate
-
-
1-(dimethoxyphosphoryl)ethyl (4-fluorophenoxy)acetate
-
-
2,2'-Dithiopyridine
-
1.1 mM, 30% inhibition
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (2,3-dichlorophenoxy)acetate
-
-
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (2-chloro-5-methylphenoxy)acetate
-
-
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (3-fluorophenoxy)acetate
-
-
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (4-chloro-2-methylphenoxy)acetate
-
-
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (4-chloro-3-methylphenoxy)acetate
-
-
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (4-chlorophenoxy)acetate
-
-
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (4-fluorophenoxy)acetate
-
-
2,3-Butanedione
Pigeon
-
10 mM, biphasic kinetic, complete inactivation after 20 min
2-p-Toluidinonaphthalene-6-sulfonate
-
-
3-Bromopyruvate
-
suicide substrate
3-Bromopyruvate
-
-
5,5'-dithiobis(2-nitrobenzoate)
Pigeon
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
1.1 mM, 35% inhibition
acetaldehyde
-
weak
acetyl-CoA
-
reversed by CoA
acetyl-CoA
-
-
acetylmethylphosphinate
-
partially reversible tight-binding inhibitor, formation of a C2alpha-phosphinolactylthiamine diphosphate derivative involving H63 residue of enzyme
Acetylphosphinate
-
partially reversible tight-binding inhibitor, formation of a C2alpha-phosphinolactylthiamine diphosphate derivative involving H63 residue of enzyme
AgNO3
-
18 mol per mol enzyme, complete inhibition
alpha-Ketobutyric acid
-
-
alpha-Ketocaproate
-
-
alpha-ketooctanoic acid
-
-
alpha-ketovalerate
-
-
Aluminium sulfate
-
1.1 mM, 35% inhibition
Ba2+
-
0.11 mM, 10% inhibition
beta-Hydroxypyruvate
-
-
beta-Hydroxypyruvate
-
competitive vs. pyruvate
beta-Hydroxypyruvate
-
noncompetitive vs. pyruvate
Cd2+
-
0.032 mM, complete inhibition
citrate
-
noncompetitive inhibition
citrate
-
0.25 mM, 29% inhibition, 50.0 mM, 87% inhibition
Cu2+
-
0.36 mM, complete inhibition
D-glucose
-
treatment of cardiac fibroblasts with 35 mM D-glucose for 72 h reduces the PDH activity remarkably. 0.2 mM thiamine dramatically recovers the high glucose-induced PDH inhibition
diethyldicarbonate
Pigeon
-
-
EDTA
-
0.036 mM, 40% inhibition, 0.36 mM, complete inhibition, reversed by addition of excess Mg2+ and Ca2+
Fluoropyruvate
-
irreversible, protection by dihydrolipoamide
Fluoropyruvate
-
-
Fluoropyruvate
-
competitive with respect to pyruvate, both free and complex bound enzyme behave in the same manner
Fluoropyruvate
-
acts as substrate analogue, competitive
gibberellin
-
modulates the activity of enzyme by regulating the expression of pyruvate dehydrogenase kinase1 and subsequently controlling plant growth and development
glyoxylate
-
competitive vs. pyruvate
glyoxylate
-
noncompetitive vs. pyruvate
glyoxylic acid
-
weak
GTP
-
5 mM, about 50% inhibition after 3 h
illumination
-
mitochondrial pyruvate dehydrogenase complex
-
KCl
-
at 2 M, 50% residual activity of enzyme expressed in Escherichia coli
L-lactate
-
weak
methyl acetylphosphonate
-
phosphonate analogue of pyruvate, leading to formation of a stable 1,4-imino-2-alpha-phosphonolactyl-thiamindiphosphate
Methylacetylphosphonate
-
-
MgATP2-
-
due to phosphorylation of the enzyme by pyruvate dehydrogenase kinase
MgATP2-
-
5 mM, 93% inhibition due to phosphorylation
MgATP2-
-
5 mM, about 70% inhibition after 3 h
Mn2+
-
0.72 mM
N-ethylmaleimide
-
1.1 mM, 50% inhibition
NaBH4
-
rapid inactivation in the presence of thiamine diphosphate, may reduce thiamine diphosphate to produce a reversible inhibitor
NaCl
-
at 2 M, 50% residual activity of enzyme expressed in Escherichia coli
O,O-dimethyl (2,3-dichlorophenoxyacetoxy)(furan-2-yl)-methylphosphonate
-
-
O,O-dimethyl (2,3-dichlorophenoxyacetoxy)(thien-2-yl)-methylphosphonate
-
-
O,O-dimethyl (2,4-dichlorophenoxyacetoxy)(furan-2-yl)-methylphosphonate
-
-
O,O-dimethyl (2,4-dichlorophenoxyacetoxy)(thien-2-yl)-methylphosphonate
-
-
O,O-dimethyl (2,6-dichlorophenoxyacetoxy)(furan-2-yl)-methylphosphonate
-
-
O,O-dimethyl (2,6-dichlorophenoxyacetoxy)(thien-2-yl)-methylphosphonate
-
-
O,O-dimethyl (2-chloro-5-methylphenoxyacetoxy)(furan-2-yl)methylphosphonate
-
-
O,O-dimethyl (2-chloro-5-methylphenoxyacetoxy)(thien-2-yl)methylphosphonate
-
-
O,O-dimethyl (3-fluorophenoxyacetoxy)(furan-2-yl)methylphosphonate
-
-
O,O-dimethyl (3-fluorophenoxyacetoxy)(thien-2-yl)methylphosphonate
-
-
O,O-dimethyl (4-chloro-2-methylphenoxyacetoxy)(furan-2-yl)methylphosphonate
-
-
O,O-dimethyl (4-chloro-2-methylphenoxyacetoxy)(thien-2-yl)methylphosphonate
-
-
O,O-dimethyl (4-chloro-3-methylphenoxyacetoxy)(furan-2-yl)methylphosphonate
-
-
O,O-dimethyl (4-chloro-3-methylphenoxyacetoxy)(thien-2-yl)methylphosphonate
-
-
O,O-dimethyl (4-chlorophenoxyacetoxy)(furan-2-yl)methylphosphonate
-
-
O,O-dimethyl (4-chlorophenoxyacetoxy)(thien-2-yl)methylphosphonate
-
-
O,O-dimethyl (4-fluorophenoxyacetoxy)(furan-2-yl)methylphosphonate
-
-
p-chloromercuribenzenesulfonate
-
8 mol per mol enzyme, complete inhibition
p-chloromercuribenzoate
Pigeon
-
0.026 mM, complete inactivation after 80 s
p-chloromercuribenzoate
-
8 mol per mol enzyme, complete inhibition
PDC kinase II
-
phosphorylates and inactivates Pda1p
-
Phenylglyoxal
Pigeon
-
10 mM, biphasic kinetic, complete inactivation after 30 min
phenylpyruvate
-
-
Phosphorylation
-
-
-
Phosphorylation
-
-
-
Phosphorylation
-
-
-
Phosphorylation
-
-
-
Phosphorylation
-
phosphorylation inactivates recombinant alpha2,beta2 tetramer in about 10 min
-
protein Pkp1p
-
phosphorylates and inactivates Pda1p
-
Pyruvamide
-
acts as substrate analogue, competitive
pyruvate dehydrogenase kinase
-
deactivates PDH by phosphorylation
-
pyruvate dehydrogenase kinase
-
phosphorylation of E1p by pyruvate dehydrogenase kinase isoforms inactivates the pyruvate dehydrogenase complex
-
Sodium diphosphate
-
competitive vs. thiamine diphosphate
sodium methyl [[[(2,4-dichlorophenoxy)acetyl]oxy](2,4-dichlorophenyl)methyl]phosphonate
-
-
sodium methyl [[[(2,4-dichlorophenoxy)acetyl]oxy](3-nitrophenyl)methyl]phosphonate
-
-
sodium methyl [[[(2,4-dichlorophenoxy)acetyl]oxy](4-fluorophenyl)methyl]phosphonate
-
-
sodium methyl [[[(2,4-dichlorophenoxy)acetyl]oxy](4-methoxyphenyl)methyl]phosphonate
-
-
sodium methyl [[[(2,4-dichlorophenoxy)acetyl]oxy](phenyl)methyl]phosphonate
-
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(2-chlorophenyl)methylphosphonate
-
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(3,4-dichlorophenyl)methyl phosphonate
-
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(4-chlorophenyl)methylphosphonate
-
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(4-methylphenyl)methylphosphonate
-
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(furan-2-yl)methylphosphonate
-
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(pyridin-2-yl)methylphosphonate
-
-
tellurite
-
pyruvate dehydrogenase activity decreases by 81% after tellurite treatment (0.0005 mg/ml for 30 min)
-
Tetrahydrothiamine diphosphate
-
cis-isomer, 0.0013 mM, 50% inhibition
thiamine 2-thiazolone diphosphate
-
crystallization data of complex with enzyme
-
thiamine 2-thiothiazolone diphosphate
-
-
thiamine 2-thiothiazolone diphosphate
-
-
thiamine thiazolone diphosphate
P0AFG8
inhibits potently the E1 component of the pyruvate dehydrogenase multienzyme complex PDHc, competitive to cofactor thiamine diphosphate, binding structure and determinants, binding induced reorganisation of the active site conformation, mechanism, K392 is important, overview
thiamine thiazolone diphosphate
-
-
thiamine thiothiazolone diphosphate
-
-
tryptamine-4,5-dione
-
inhibition is blocked by reduced glutathione or cysteine at large molar excess, ascorbate protects partially
Moniliformin
-
0.3 mM, 82% inhibition
additional information
-
not inhibited by ATP
-
additional information
-
not inhibited by ATP
-
additional information
-
not inhibited by ATP
-
additional information
-
enzyme from chloroplast is not inhibited by ATP
-
additional information
-
not inhibited by ATP
-
additional information
-
effects of several plant hormones and auxin derivatives
-
additional information
-
PDH activity can be downregulated by an increase in dietary fat, attenuated PHD contributes to the preferential oxidation of n-6 poly unsaturated fatty acids during moderate-intensity exercis
-
additional information
-
pyruvate dehydrogenase complex inhibition occurs via enhanced expression of pyruvate dehydrogenase kinase-1, which results in inhibitory phosphorylation of the pyruvate dehydrogenase alpha subunit, knockdown of pyruvate dehydrogenase kinase-1 via short hairpin RNA lowers inhibitory PDHalpha phosphorylation
-
additional information
-
there is no significant change in the PDH activity in the presence of D-mannitol (35 mM)
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ADP
-
stimulates
AMP
-
ascites tumour cells, 1 mM, about 2fold activation of pyruvate dehydrogenase
cAMP
-
ascites tumour cells
dobutamine
-
increases pyruvate dehydrogenase complex activity
fatty acid transport protein 1
-
enhances mitochondrial pyruvate dehydrogenase activity
-
GMP
-
ascites tumour cells
PDC phosphatase II
-
dephosphorylates and reactivates phosphorylated Pda1p
-
protein Ppp1p
-
dephosphorylates and reactivates phosphorylated Pda1p
-
pyruvate dehydrogenase kinase
-
dephosphorylation by pyruvatedehydrogenase phosphatase isoforms restores pyruvate dehydrogenase complex activity
-
pyruvate dehydrogenase phosphatase
-
PDC is dephosphorylated and to completely activated with pyruvate dehydrogenase phosphatase
-
pyruvate dehydrogenase phosphatase
-
activates PDH by dephosphorylation
-
spermine
-
in the absence of exogenous Ca2+ and Mg2+ and in the presence of EGTA, which favours the release of endogenous Ca2+, spermine is able to stimulate the activity of pyruvate dehydrogenase complex (maximum stimulation of about 140% at 0.5mM after 30 min of incubation, at concentrations higher than 0.5mM, spermine still stimulates PDC, when compared with the control, but shows a slight dose-dependent decrease). The interaction of spermine with PDC may also involve activation of pyruvate dehydrogenase kinase, resulting in an increase in E1alpha phosphorylation and consequently reduced stimulation of PDC at high polyamine concentrations
thiamine diphosphate
-
exogenous addition activates, involved in conformational changes
GTP
-
1-10 mM, slight activation
additional information
-
no activation with AMP in adrenal medulla
-
additional information
-
no activation with AMP in liver and heart
-
additional information
-
enzyme complex activity is increased with high workload and energy expenditure in the myocardium
-
additional information
-
effects of several plant hormones and auxin derivatives
-
additional information
-
the E1alpha subunit of PDC regulates the activity of the complex
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.7
2-keto-4-methylhexanoate
-
mutant I472A, 30C, pH 6.5
3.7
2-keto-4-methylhexanoate
-
mutant I472A/I476F, 30C, pH 6.5
40
2-keto-4-methylhexanoate
-
wild-type, 30C, pH 6.5
4.7
2-ketobutanoate
-
wild-type, 30C, pH 6.5
6.7
2-ketobutanoate
-
mutant I472A, 30C, pH 6.5
50
2-ketobutanoate
-
mutant I472A/I476F, 30C, pH 6.5
0.166
2-Ketobutyrate
-
-
0.2
2-ketohexanoate
-
mutant I472A, 30C, pH 6.5
0.5
2-ketohexanoate
-
mutant I472A/I476F, 30C, pH 6.5
12.7
2-ketohexanoate
-
wild-type, 30C, pH 6.5
0.2
2-ketopentanoate
-
mutant I472A/I476F, 30C, pH 6.5
2.5
2-ketopentanoate
-
mutant I472A, 30C, pH 6.5
7.6
2-ketopentanoate
-
wild-type, 30C, pH 6.5
1.8
benzoylformate
-
mutant I472A, 30C, pH 6.5
4.4
benzoylformate
-
mutant I472A/I476F, 30C, pH 6.5
0.004
CoA
-
2-oxoglutarate dehydrogenase complex, pH 7.6, 30C, in presence of thiamine diphosphate
0.012
CoA
-
2-oxoglutarate dehydrogenase complex, pH 7.6, 30C, in absence of thiamine diphosphate
0.003
coenzyme A
-
assay with whole enzyme complex
0.73
E2p lipoyl domain
-
wild type enzyme, at pH 7.0 and 30C
-
0.02
lipoyl domain
-
-
-
0.024
lipoyl domain
-
acyl group transfer reaction, recombinant pyruvate dehydrogenase with N-terminal deletion
-
0.027
lipoyl domain
-
acyl group transfer reaction, recombinant wild-type pyruvate dehydrogenase
-
0.36
Mg2+
-
whole enzyme complex
15
N-acetyl-GDLLAEIETDK(lipoyl)-ATIG-amide
-
-
0.052
N-terminal lipoyl domain
-
-
-
0.033
NAD+
-
2-oxoglutarate dehydrogenase complex, pH 7.6, 30C, in presence of thiamine diphosphate
0.051
NAD+
-
assay with whole enzyme complex
0.07
NAD+
-
2-oxoglutarate dehydrogenase complex, pH 7.6, 30C, in absence of thiamine diphosphate
0.0002
pyruvate
-
2-oxoglutarate dehydrogenase complex, pH 7.6, 30C, in presence of thiamine diphosphate, in presence of 2 mM Mn2+
0.0006
pyruvate
-
2-oxoglutarate dehydrogenase complex, pH 7.6, 30C, in presence of thiamine diphosphate, in presence of 2 mM Ca2+
0.0007
pyruvate
-
2-oxoglutarate dehydrogenase complex, pH 7.6, 30C, in absence of thiamine diphosphate, in presence of 2 mM Mn2+
0.0011
pyruvate
-
wild-type enzyme, pH 7.0, 25C
0.0012
pyruvate
-
mutant F266A, pH 7.0, 25C
0.0016
pyruvate
-
2-oxoglutarate dehydrogenase complex, pH 7.6, 30C, in absence of thiamine diphosphate, in presence of 2 mM Ca2+
0.0021
pyruvate
-
mutant S283C, pH 7.0, 25C
0.0088
pyruvate
-
mutant R282A, pH 7.0, 25C
0.01
pyruvate
-
pH 7.6, 30C, presence of 0.3 M KCl
0.011
pyruvate
-
mutant D276A, pH 7.0, 25C
0.017
pyruvate
Pigeon
-
-
0.017
pyruvate
-
similar values
0.017
pyruvate
-
similar values
0.0204
pyruvate
-
recombinant enzyme
0.0226
pyruvate
-
pH 7.0, 37C, mutant S271A of isoform PDH2
0.023
pyruvate
-
2-oxoglutarate dehydrogenase complex, pH 7.6, 30C, in presence of thiamine diphosphate, without divalent cations
0.0248
pyruvate
-
-
0.0258
pyruvate
-
pH 7.0, 37C, mutant S271E of isoform PDH2
0.026
pyruvate
-
recombinant enzyme
0.0263
pyruvate
-
pH 7.0, 37C, mutant S203A of isoform PDH2
0.027
pyruvate
-
pH 7.6, 30C, catalytic subunit E1
0.0359
pyruvate
-
pH 7.0, 37C, isoform PDH2
0.049
pyruvate
-
mutant Y281A/R282A/S283A, pH 7.0, 25C
0.056
pyruvate
-
mutant Y281A/R282A, pH 7.0, 25C
0.0565
pyruvate
-
pH 7.0, 37C, mutant S203E of isoform PDH2
0.063
pyruvate
-
mutant Y281A, pH 7.0, 25C
0.063
pyruvate
-
2-oxoglutarate dehydrogenase complex, pH 7.6, 30C, in absence of thiamine diphosphate and divalent cations
0.0648
pyruvate
-
pH 7.0, 37C, isoform PDH1
0.066
pyruvate
-
mutant Y281S/R282S, pH 7.0, 25C
0.072
pyruvate
-
pH 7.6, 30C, overall reaction of complex
0.09
pyruvate
-
assay with whole enzyme complex
0.1304
pyruvate
-
mutant enzyme Q408A, with 2,6-dichlorophenolindophenol, at 30C
0.14
pyruvate
-
assay with whole enzyme complex
0.14
pyruvate
-
in the presence of Ca2+ and Mg2+
0.1714
pyruvate
-
mutant enzyme K410A, with 2,6-dichlorophenolindophenol, at 30C
0.2012
pyruvate
-
mutant enzyme K411E, with 2,6-dichlorophenolindophenol, at 30C
0.2336
pyruvate
-
mutant enzyme K411A, with 2,6-dichlorophenolindophenol, at 30C
0.25
pyruvate
-
-
0.25
pyruvate
-
-
0.25
pyruvate
-
-
0.2609
pyruvate
-
wild type enzyme, with 2,6-dichlorophenolindophenol, at 30C
0.28
pyruvate
-
Y177A mutant enzyme
0.291
pyruvate
-
mutant R267A, pH 7.0, 25C
0.515
pyruvate
-
wild-type enzyme
0.531
pyruvate
-
Y177F mutant enzyme
0.6286
pyruvate
-
mutant enzyme E401A, with 2,6-dichlorophenolindophenol, at 30C
0.65
pyruvate
-
assay with whole enzyme complex
0.7008
pyruvate
-
mutant enzyme K403A, with 2,6-dichlorophenolindophenol, at 30C
1.1
pyruvate
-
wild-type, 30C, pH 6.5
1.7
pyruvate
Q8NNF6
30C, cell extract
2.6
pyruvate
-
mutant I476F, 30C, pH 6.5
7.8
pyruvate
-
mutant I472A, 30C, pH 6.5
50
pyruvate
-
mutant I472A/I476F, 30C, pH 6.5
0.00008
thiamine diphosphate
-
whole enzyme complex
0.00056
thiamine diphosphate
-
mutant R267A, pH 7.0, 25C
0.0009
thiamine diphosphate
-
recombinant enzyme
0.0015
thiamine diphosphate
-
recombinant enzyme
0.00158
thiamine diphosphate
-
wild-type enzyme
0.0027
thiamine diphosphate
-
mutant Y281S/R282S, pH 7.0, 25C
0.0029
thiamine diphosphate
-
mutant Y281A/R282A/S283A, pH 7.0, 25C
0.003
thiamine diphosphate
-
mutant Y281A/R282A, pH 7.0, 25C
0.0052
thiamine diphosphate
-
mutant R282A, pH 7.0, 25C
0.0055
thiamine diphosphate
-
mutant Y281A, pH 7.0, 25C
0.00665
thiamine diphosphate
-
Y177A mutant enzyme
0.013
thiamine diphosphate
-
mutant S283C, pH 7.0, 25C
0.021
thiamine diphosphate
-
mutants F266A and D276A, pH 7.0, 25C
0.023
thiamine diphosphate
-
wild-type enzyme, pH 7.0, 25C
0.05
thiamine diphosphate
-
-
0.065
thiamine diphosphate
-
in the presence of Ca2+ and Mg2+
1
Mg2+
-
-
additional information
additional information
-
sigmoidal dependence on the concentration of pyruvate, Hill-coefficient: 1.85
-
additional information
additional information
-
with aging of rats the Vmax of the enzyme complex increases by 60%, while the Km decreases by 1.6fold in the same time, enzyme expression level remaines constant, more efficient catabolization of pyruvate due to adaptive phosphorylation of the enzyme within the multienzyme complex, age-related decline in pyruvate dehydrogenase kinase PDK-4
-
additional information
additional information
-
kinetic and thermodynamic analysis
-
additional information
additional information
-
kinetics
-
additional information
additional information
-
kinetic study, reaction of pyruvate dehydrogenase complex
-
additional information
additional information
-
detailed kinetic and thermodynamic analysis
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.4
2-keto-4-methylhexanoate
-
wild-type, 30C, pH 6.5
7.7
2-keto-4-methylhexanoate
-
mutant I472A, 30C, pH 6.5
8.1
2-keto-4-methylhexanoate
-
mutant I472A/I476F, 30C, pH 6.5
9
2-ketobutanoate
-
mutant I472A/I476F, 30C, pH 6.5
32
2-ketobutanoate
-
mutant I476F, 30C, pH 6.5
250
2-ketobutanoate
-
mutant I472A, 30C, pH 6.5
320
2-ketobutanoate
-
wild-type, 30C, pH 6.5
0.8
2-ketohexanoate
-
mutant I476F, 30C, pH 6.5
4
2-ketohexanoate
-
wild-type, 30C, pH 6.5
82
2-ketohexanoate
-
mutant I472A/I476F, 30C, pH 6.5
130
2-ketohexanoate
-
mutant I472A, 30C, pH 6.5
11
2-ketopentanoate
-
mutant I476F, 30C, pH 6.5
30
2-ketopentanoate
-
mutant I472A/I476F, 30C, pH 6.5
53
2-ketopentanoate
-
wild-type, 30C, pH 6.5
220
2-ketopentanoate
-
mutant I472A, 30C, pH 6.5
1.2
benzoylformate
-
mutant I472A/I476F, 30C, pH 6.5
6.9
benzoylformate
-
mutant I472A, 30C, pH 6.5
0.08
E2p lipoyl domain
-
mutant enzyme H407A, at pH 7.0 and 30C
-
0.7
E2p lipoyl domain
-
mutant enzyme D549A, at pH 7.0 and 30C
-
0.83
E2p lipoyl domain
-
mutant enzyme E401K, at pH 7.0 and 30C
-
3.31
E2p lipoyl domain
-
mutant enzyme Y177A, at pH 7.0 and 30C
-
95
E2p lipoyl domain
-
wild type enzyme, at pH 7.0 and 30C
-
0.9
lipoyl domain
-
acyl group transfer reaction, recombinant wild-type pyruvate dehydrogenase
-
1.1
lipoyl domain
-
acyl group transfer reaction, recombinant pyruvate dehydrogenase with N-terminal deletion
-
5
N-acetyl-GDLLAEIETDK(lipoylated)ATIG-amide
-
-
26.3
N-terminal lipoyl domain
-
-
-
70
N-terminal lipoyl domain
-
pyruvate dehydrogenase preparation with high activity
-
0.077
pyruvate
-
pH 7.6, 30C, presence of 0.3 M KCl
0.081
pyruvate
-
mutant enzyme H407A, with 2,6-dichlorophenolindophenol, at 30C
0.21
pyruvate
-
mutant enzyme K403E, with 2,6-dichlorophenolindophenol, at 30C
0.3
pyruvate
-
mutant F266A, pH 7.0, 25C
0.38
pyruvate
-
mutant S283C, pH 7.0, 25C
0.39
pyruvate
-
mutant enzyme E401K, with 2,6-dichlorophenolindophenol, at 30C
0.48
pyruvate
-
wild-type enzyme, pH 7.0, 25C
0.55
pyruvate
-
mutant R282A, pH 7.0, 25C
0.71
pyruvate
-
mutant D276A, pH 7.0, 25C
0.82
pyruvate
-
mutant Y281A, pH 7.0, 25C
0.96
pyruvate
-
mutant Y281A/R282A, pH 7.0, 25C
1.21
pyruvate
-
mutant Y281S/R282S, pH 7.0, 25C
1.23
pyruvate
-
mutant Y281A/R282A/S283A, pH 7.0, 25C
1.53
pyruvate
-
mutant enzyme K410E, with 2,6-dichlorophenolindophenol, at 30C
1.62
pyruvate
-
mutant R267A, pH 7.0, 25C
3.07
pyruvate
-
mutant enzyme N404A, with 2,6-dichlorophenolindophenol, at 30C
3.64
pyruvate
-
mutant enzyme E401A, with 2,6-dichlorophenolindophenol, at 30C
4.41
pyruvate
-
mutant enzyme K403A, with 2,6-dichlorophenolindophenol, at 30C
7.68
pyruvate
-
mutant enzyme K410A, with 2,6-dichlorophenolindophenol, at 30C
8
pyruvate
-
mutant I472A/I476F, 30C, pH 6.5
19.03
pyruvate
-
mutant enzyme Q408A, with 2,6-dichlorophenolindophenol, at 30C
25.12
pyruvate
-
mutant enzyme K411E, with 2,6-dichlorophenolindophenol, at 30C
26
pyruvate
-
pH 7.0, 37C, mutant S271E of isoform PDH2
29.2
pyruvate
-
pH 7.0, 37C, mutant S203A of isoform PDH2
32.6
pyruvate
-
pH 7.0, 37C, mutant S271A of isoform PDH2
35.13
pyruvate
-
mutant enzyme K411A, with 2,6-dichlorophenolindophenol, at 30C
37.9
pyruvate
-
wild type enzyme, with 2,6-dichlorophenolindophenol, at 30C
38.1
pyruvate
-
pH 7.0, 37C, mutant S203E of isoform PDH2
66.1
pyruvate
-
pH 7.0, 37C, isoform PDH2
69.9
pyruvate
-
pH 7.0, 37C, isoform PDH1
77
pyruvate
-
mutant I476F, 30C, pH 6.5
200
pyruvate
-
mutant I472A, 30C, pH 6.5
486
pyruvate
-
wild-type, 30C, pH 6.5
0.35
thiamine diphosphate
-
mutant F266A, pH 7.0, 25C
0.45
thiamine diphosphate
-
mutant S283C, pH 7.0, 25C
0.46
thiamine diphosphate
-
wild-type enzyme, pH 7.0, 25C
0.62
thiamine diphosphate
-
mutant R282A, pH 7.0, 25C
0.91
thiamine diphosphate
-
mutant D276A, pH 7.0, 25C
0.97
thiamine diphosphate
-
mutant Y281A, pH 7.0, 25C
0.98
thiamine diphosphate
-
mutant Y281A/R282A, pH 7.0, 25C
1.25
thiamine diphosphate
-
mutant R267A, pH 7.0, 25C
1.3
thiamine diphosphate
-
mutant Y281S/R282S, pH 7.0, 25C
1.39
thiamine diphosphate
-
mutant Y281A/R282A/S283A, pH 7.0, 25C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0006
2-p-Toluidinonaphthalene-6-sulfonate
-
assay with whole enzyme complex, competitive inhibition
0.02
acetyl-CoA
-
competitive inhibition vs. CoA, whole enzyme complex
0.00146
acetylmethylphosphinate
-
pH 8.0, 30C
0.0033
acetylmethylphosphinate
-
pH 8.0, 30C
0.000014
Acetylphosphinate
-
pH 8.0, 30C
0.00076
Acetylphosphinate
-
pH 8.0, 30C
2.25
alpha-Ketobutyric acid
-
assay with whole enzyme complex
1
beta-Hydroxypyruvate
-
assay with whole enzyme complex
0.028
Bromopyruvate
-
assay with whole enzyme complex
8.6
citrate
-
-
0.0014
Fluoropyruvate
-
assay with whole enzyme complex
0.018
Fluoropyruvate
-
-
0.02
Fluoropyruvate
-
pH 7.6, 30C, overall reaction of complex
0.3
glyoxylate
-
assay with whole enzyme complex, competitive inhibition
3.27
glyoxylate
-
-
0.5
glyoxylic acid
-
assay with whole enzyme complex
0.11
Hydroxypyruvate
-
-
0.015
NADH
-
competitive inhibition vs. NAD+, whole enzyme complex
0.02
Pyruvamide
-
pH 7.6, 30C, overall reaction of complex
31
pyruvate
-
recombinant wild-type pyruvate dehydrogenase
37
pyruvate
-
recombinant pyruvate dehydrogenase with N-terminal deletion
0.51
Sodium diphosphate
-
-
0.000003
thiamine 2-thiazolone diphosphate
-
-
-
0.000064
thiamine 2-thiothiazolone diphosphate
-
-
0.0000737
thiamine 2-thiothiazolone diphosphate
-
-
0.003
thiamine thiazolone diphosphate
P0AFG8
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00085
-
enzyme from chloroplast
0.00265
-
enzyme from chloroplast
0.0048
-
Y177A mutant enzyme, 2,6-dichlorophenolindophenol assay, substrate 2alpha-hydroxyethyl-thiamin diphosphate
0.00485
-
enzyme from mitochondrion
0.00574
A2TC23
in cells grown on 50 mM glucose and 2 mM acetate, at 22C
0.00671
-
Y177F mutant enzyme, 2,6-dichlorophenolindophenol assay, substrate 2alpha-hydroxyethyl-thiamin diphosphate
0.0098
-
wild-type enzyme, 2,6-dichlorophenolindophenol assay, substrate 2alpha-hydroxyethyl-thiamin diphosphate
0.01
-
mutant I476F, substrate benzoylformate, 30C, pH 6.5
0.011
A2TC23
in cells grown on 50 mM glycerol and 2 mM acetate, at 22C
0.0162
-
recombinant His-tagged-alpha2,beta2 tetramer, assay with 2-hydroxyethylidene-thiamine diphosphate and 2,6-dichlorphenolindophenol
0.0269
-
recombinant His-tagged-alpha2,beta2 tetramer, assay with pyruvate and 2,6-dichlorphenolindophenol
0.035
-
pyruvate as substrate, pyruvate dehydrogenase preparation with high activity
0.0513
-
assay with whole enzyme complex
0.063
-
decarboxylation in the absence of K3Fe(CN)6 as artificial electron acceptor
0.085
-
pyruvate-K3Fe(CN)6 reductase assay
0.087
-
Y177A mutant enzyme, 2,6-dichlorophenolindophenol assay, substrate pyruvate
0.13
-
recombinant alpha2beta2 tetramer
0.14
-
pyruvate-K3Fe(CN)6 reductase assay
0.1416
-
decarboxylation in the presence of K3Fe(CN)6 as artificial electron acceptor
0.145
-
recombinant alpha2,His-tagged-beta2 tetramer, K3Fe(CN)6 as artificial electron acceptor
0.16
-
N-terminal lipoyl domain as substrate, pyruvate dehydrogenase preparation with high activity
0.18
-
recombinant alpha2,beta2 tetramer with six histidine residues attached to the N-terminus
0.187
-
recombinant His-tagged-alpha2,beta2 tetramer, K3Fe(CN)6 as artificial electron acceptor
0.2
-
pyruvate-K3Fe(CN)6 reductase assay
0.2
-
mutant I476F, substrate 2-ketohexanoate, 30C, pH 6.5; wild-type, substrate 2-ketohexanoate, 30C, pH 6.5
0.216
-
Y177F mutant enzyme, 2,6-dichlorophenolindophenol assay, substrate pyruvate
0.367
-
recombinant alpha2,His-tagged-beta2 tetramer, assay with pyruvate and 2,6-dichlorphenolindophenol
0.385
-
purified recombinant wild-type E1, with 2,6-dichlorophenolindophenol as electron acceptor
0.445
-
wild-type enzyme, 2,6-dichlorophenolindophenol assay, substrate pyruvate
0.5
-
mutant I472A/I472A, substrate benzoylformate, 30C, pH 6.5
1.5
-
mutant I472A, substrate 2-keto-4-methylhexanoate, 30C, pH 6.5; mutant I472A, substrate benzoylformate, 30C, pH 6.5
2
-
mutant I472A/I472A, substrate pyruvate, 30C, pH 6.5
2.2
-
mutant I472A/I472A, substrate 2-ketobutanoate, 30C, pH 6.5
2.5
-
mutant I472A/I472A, substrate 2-keto-4-methylhexanoate, 30C, pH 6.5
2.7
-
mutant I476F, substrate 2-ketopentanoate, 30C, pH 6.5
3.26
-
recombinant enzyme from testis
5.7
-
assay with whole enzyme complex
7.3
-
mutant I472A/I472A, substrate 2-ketopentanoate, 30C, pH 6.5
8
-
mutant I476F, substrate 2-ketobutanoate, 30C, pH 6.5
8.13
-
recombinant enzyme from liver
10.9
-
recombinant alpha2,His-tagged-beta2 tetramer, reduction of NAD+, overall reaction
13
-
wild-type, substrate 2-ketopentanoate, 30C, pH 6.5
14.4
-
recombinant His-tagged-alpha2,beta2 tetramer, reduction of NAD+, overall reaction
15.8
-
reduction of NAD+, overall reaction
19
-
mutant I476F, substrate pyruvate, 30C, pH 6.5
20
-
mutant I472A/I472A, substrate 2-ketohexanoate, 30C, pH 6.5
24.6
-
pH 7.0, 37C, isoform PDH2
25.9
-
pH 7.0, 37C, isoform PDH1
28.35
-
purified recombinant wild-type E1, with NAD+ as electron acceptor
32
-
mutant I472A, substrate 2-ketohexanoate, 30C, pH 6.5
50
-
mutant I472A, substrate pyruvate, 30C, pH 6.5
54
-
mutant I472A, substrate 2-ketopentanoate, 30C, pH 6.5
55
-
recombinant enzyme from Haloferax volcanii
62
-
mutant I472A, substrate 2-ketobutanoate, 30C, pH 6.5
79
-
wild-type, substrate 2-ketobutanoate, 30C, pH 6.5
91
-
recombinant enzyme from Escherichia coli
120
-
wild-type, substrate pyruvate, 30C, pH 6.5
1791
-
activity after reassociation of the purified enzyme with EC 2.3.1.12 and EC 1.8.1.4
additional information
-
measurement of NADH/NAD+ and acetyl-CoA/CoA ratios, and citric acid cycle intermediates in blood and tissue, measurement of O2-uptake and fatty acid and glucose oxidation level
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 7
-
with Mg2+ as divalent cation
6.5 - 7.5
-
-
6.5 - 7.5
-
with Ca2+ as divalent cation
7
-
wild-type pyruvate dehydrogenase and N-terminal deletion mutant
7.4
-
assay at
7.6
-
assay at
7.6
-
assay at
additional information
-
-
additional information
-
-
additional information
-
value for pyruvate dehydrogenase complex: 8.2, chloroplast enzyme
additional information
-
value for pyruvate dehydrogenase complex: 8.0
additional information
Hansenula sp.
-
-
additional information
Pigeon
-
value for pyruvate dehydrogenase complex: 7.7
additional information
-
value for pyruvate dehydrogenase complex: 7.5-8.2
additional information
-
value for pyruvate dehydrogenase complex: 7.0-7.4
additional information
-
value for pyruvate dehydrogenase complex: 7.5
additional information
-
value for pyruvate dehydrogenase complex: 7.6
additional information
-
value for pyruvate dehydrogenase complex: 7.0-7.4
additional information
-
value for pyruvate dehydrogenase complex: 8.0-9.0
additional information
-
value for pyruvate dehydrogenase complex: 7.7-8.1
additional information
-
value for pyruvate dehydrogenase complex: 7.8
additional information
-
value for pyruvate dehydrogenase complex: 7.6
additional information
-
value for pyruvate dehydrogenase complex: 6.0
additional information
-
value for pyruvate dehydrogenase complex: 7.8-8.3
additional information
-
dependency on buffer system
additional information
-
value for pyruvate dehydrogenase complex: 7.7
additional information
Hansenula miso
-
-
additional information
-
value for pyruvate dehydrogenase complex: 8.0-9.0
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
values for pyruvate dehydrogenase complex: pH 7.1-8.8
additional information
-
values for pyruvate dehydrogenase complex: pH 6.8-8.8
additional information
-
values for pyruvate dehydrogenase complex: pH 6.5-9.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
-
assay at
70
-
wild-type enzyme
additional information
-
values for pyruvate dehydrogenase complex: 35-50C
additional information
-
value for pyruvate dehydrogenase complex: 70C
additional information
-
value for pyruvate dehydrogenase complex: 64C
additional information
-
value for pyruvate dehydrogenase complex: 48C
additional information
-
value for pyruvate dehydrogenase complex: 72C
additional information
-
value for pyruvate dehydrogenase complex: 45C
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
15 - 50
-
value for pyruvate dehydrogenase complex
additional information
-
temperature dependence of wild-type and mutant enzymes
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
non-small cell lung carcinoma
Manually annotated by BRENDA team
Enterobacter cloacae 501R3
-
50 mM glucosel and 2 mM acetate
-
Manually annotated by BRENDA team
Enterobacter cloacae 501R3
-
50 mM glycerol and 2 mM acetate
-
Manually annotated by BRENDA team
-
type 2 variant of the E1alpha subunit, most abundant expression
Manually annotated by BRENDA team
-
from 4-, and 24- to 28-months-old male F344 rats
Manually annotated by BRENDA team
-
testis-specific isoform PDH2
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
relict plastid, fusion of two-part leader sequence of enzyme to green fluorescent protein confirms apicoplast localization
Manually annotated by BRENDA team
Q1KSF0
exclusively localized to the apicoplast
Manually annotated by BRENDA team
-
the PDH E1a and E3 subunits colocalize with the FAS II enzyme FabI in the apicoplast of liver stages but are not significantly expressed in blood stages
Manually annotated by BRENDA team
-
subunit E1, EC 1.2.4.1, of whole enzyme complex has lower affinity to membrane than E2, EC 1.8.1.4
Manually annotated by BRENDA team
-
located within the inner membrane matrix compartment
Manually annotated by BRENDA team
-
distinct from mitochondrial enzyme, different subunit composition
Manually annotated by BRENDA team
additional information
Q1KSF0
absent in the mitochondrion
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli O157:H7 (strain TW14359 / EHEC)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
43000
-
SDS-PAGE
712851
99470
P0AFG8
pyruvate dehydrogenase multienzyme complex component E1
654647
100000
-
sucrose density gradient centrifugation
348967
136000
-
gel filtration
348935
150000
-
calculation from sedimentation and diffusion data, low speed sedimentation equilibrium centrifugation, meniscus depletion method
348974
152000
-
-
675426
154000
-
-
348955, 348957, 94881
160000
-
recombinant alpha2,beta2 tetramer
348983
169000
-
whole pyruvate dehydrogenase enzyme complex, gel filtration
654734
182000 - 183000
-
light scattering
348966
182000 - 183000
-
calculation from sedimentation and diffusion data
348981
190000
-
sedimentation equilibrium centrifugation
348939
200000
-
SDS-PAGE
689791
206000
-
scanning transmission electron microscopy
348933
240000
-
gel filtration, recombinant protein from Escherichia coli and from Haloferax volcanii
663808
additional information
-
MW of native complex isolated from kidney and heart: 7000000 Da and 8500000 Da respectively
348910
additional information
-
-
348910
additional information
-
-
348914
additional information
-
MW of native complex from heart: 740000 Da
348914
additional information
-
MW of native complex isolated from kidney and heart: 7000000 Da and 8500000 Da respectively
348955
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 100000, SDS-PAGE
?
-
x * 63000, SDS-PAGE
?
-
x * 92500, SDS-PAGE
?
-
x * 40000-41000 + x * 37000
?
-
x * 40315, pyruvate dehydrogenase multienzyme complex component E1alpha, sequence calculation
?
-
x * 99474, E1, laser light scattering
?
-
x * 99474, calculated from amino acid sequence
dimer
-
2 * 100000, SDS-PAGE
dimer
-
2 * 94000, SDS-PAGE
dimer
-
2 * 99474, calculation from nucleotide sequence
dimer
-
2 * 95000-96500, SDS-PAGE with and without urea
dimer
-
alpha2,beta2, 2 * 43000 + 2 * 40000, SDS-PAGE, immunoblotting
dimer
-
alpha2,beta2, 2 * 38000 + 2 * 56000, SDS-PAGE, N-terminal amino acid sequencing
dimer
P0AFG8
pyruvate dehydrogenase multienzyme complex component E1, 3 domains with alpha/beta fold, active sites are located at the interface between subunits, crystal structure
dimer
Escherichia coli K12
-
2 * 100000, SDS-PAGE
-
heterotetramer
-
-
heterotetramer
-
x-ray crystallography
heterotetramer
-
x-ray crystallography
homodimer
-
2 * 100000, SDS-PAGE
oligomer
-
-
oligomer
-
60 * 41000 (E1 alpha) + 60 * 36000 (E1 beta) + 60 * 52000 (E2, EC 2.3.1.12) + 12 * 55000 (E3, EC 1.8.1.4) + 8-12 * 50000 (component X) + kinase and phosphatase components, heart pyruvate dehydrogenase complex
oligomer
-
quaternary structure of pyruvate dehydrogenase complex
tetramer
-
-
tetramer
-
-
tetramer
-
4 * 60000, SDS-PAGE
tetramer
-
alpha2,beta2, 2 * 41000 + 2 * 36000
tetramer
-
alpha2,beta2, 2 * 42000 + 2 * 38000, SDS-PAGE
tetramer
Pigeon
-
alpha2,beta2, 2 * 42000 + 2 * 37000, SDS-PAGE
tetramer
-
alpha2,beta2, 2 * 45000 + 2 * 35000, SDS-PAGE
tetramer
-
alpha2,beta2, 2 * 45000 + 2 * 35000, SDS-PAGE
tetramer
-
alpha2,beta2, 2 * 42000 + 2 * 36000, SDS-PAGE, calculated from gene sequence
tetramer
P52903
alpha2,beta2, 1 * 43000 + 1 * 41000 + 2 * 37000, SDS-PAGE
tetramer
-
alpha2,beta2, 2 * 41000 + 2 * 35000, SDS-PAGE
tetramer
-
alpha2beta2 structure
monomer
-
1 * 100000, SDS-PAGE
additional information
-
enzyme component organization and binding structures in the pyruvate dehydrogenase multienzyme complex, core is formed by compoenents E2 and E3, regulatory role
additional information
-
identification of key amino acid residues responsible for enzyme component assembly to the multienzyme complex, overview
additional information
-
pyruvate dehydrogenase component consists of 2 subunits E1alpha-2 and E1alpha-1
additional information
-
analysis of architecture of enzyme subunits in pyruvate dehydrogenase complex. Complex contains 30 enzyme heterotetramers plus dihydrolipoamide acetyltransferase and dihydrolipoamide dehydrogenase multimers
additional information
-
analysis of pyruvate dehydrogenase core complex consisting of dihydrolipoyl acetyltransferase and dihydrolipoyl dehydrogenase enzymes and comparison with structure of enzyme complex with dihydrolipoyl acetyltransferase
additional information
-
enzyme interacts with pirin protein. In pirin mutant, enzyme and pyruvate dehydrogenase complex activity increase by 250 and 140%, resp.
additional information
-
substrate channelling in the multienzyme complex rests on the recognition of the lipoyl domain by enzyme. Cofactor thiamine diphosphate and substrate pyruvate have distinct effects on enzyme/lipoyl domain interaction. conformational freedom is allowed by the linker in the movement of the lipoyl domain between active sites
additional information
-
the affinity of PDH2 for the PDH-binding domain of E2 of pyruvate dehydrogenase complex differs only modestly from that of PDH1, surface plasma resonance studies
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
side-chain modification
-
-
side-chain modification
-
reversible posphorylation of mammalian alpha subunit by pyruvate dehydrogenase kinase at three serine residues inactivates enzyme, dephosporylation by phosphatase activates
phosphoprotein
-
regulation of activity by pyruvate dehydrogenase kinase isoenzymes. PDK2 has the highest activity for site S264 of PDH2, PDK3 has higher activity for site S271 than for site S264, and only PDK1 can phosphorylate site S203
phosphoprotein
-
the PDC is tightly regulated by reversible phosphorylation at three known phosphorylation sites on PDHE1a: Ser293, Ser300, and Ser232
phosphorylation
-
phosphorylation of Ser264 slows the preceding binding of substrate to the enzyme's active site via the substrate channel and the subsequent reductive acetylation of the E2 component
proteolytic modification
-
cleavage of 29 amino acid long leader peptide from alpha subunit suggested from deduced protein sequence
side-chain modification
-
phosphorylation of recombinant alpha2,beta2 tetramer, 3.25 phosphoryl groups per mol tetramer are incorporated, 50% phosphorylation within 10 min, only the alpha subunit is phosphorylated
phosphoprotein
-
the PDC is tightly regulated by reversible phosphorylation at three known phosphorylation sites on PDHE1a: Ser293, Ser300, and Ser232
side-chain modification
-
inactivated by phosphorylation
side-chain modification
-
inactivated by phosphorylation
glycoprotein
-
the O-glycosylation of PDH E1alpha is involved in the regulation of the PDH activity
phosphoprotein
-
the enzyme, as pyruvate dehydrogenase multienzyme complex component E1alpha, becomes reversibly phosphorylated at 3 serine residues by specific pyruvate dehydrogenase kinases PDK1-4, and dephosphorylated by a specific pyruvate dehydrogenase phosphatase PDP-1 and to a lesser extant PDP-2, regulatory function, pyruvate oxidation is inhibited in phosphorylated state of E1alpha
phosphoprotein
-
brain aging is associated with a decrease of pyruvate dehydrogenase activity upon phosphorylation of the E1alpha subunit. Decreases in activity of about 25% and about 45% are found in mitochondria from 14- and 24-months old rats, respectively. The pyruvate dehydrogenase kinase-2-dependent inhibition of PDH activity amounts to about 20%, 43%, and 49% at 6, 14, and 24 months of age, respectively
phosphoprotein
-
PDH activity is inhibited by the phosphorylation of its E1alpha1 subunit
phosphoprotein
-
regulation of pyruvate dehydrogenase complex activity through reversible phosphorylation
side-chain modification
-
inactivated by phosphorylation
side-chain modification
-
inactivated by phosphorylation
additional information
-
not regulated by phosphorylation/dephosporylation
side-chain modification
-
inactivated by phosphorylation
additional information
-
not regulated by phosphorylation/dephosporylation
additional information
-
not regulated by phosphorylation/dephosporylation
additional information
-
not regulated by phosphorylation/dephosporylation
side-chain modification
Pigeon
-
addition of pyruvate decreases enzyme phosphyrylation and inactivation, more than 2 mol phosphate are incorporated per tetramer, modification of arginine residues by 2,3-butanedione decreases activity and prevents phosphorylation, suggesting that substrate binding sites and regulatory sites are close together
additional information
-
enzyme from chloroplast is not regulated by phosphorylation/dephosphorylation
phosphoprotein
-
phosphorylation of the PDH E1alpha subunit by PDH kinase contributes to the suppression of PDH activity. Streptozotocin treatment causes a significant increase in the level of the phosphorylated PDH E1alpha subunit in the diabetic rat hearts
additional information
-
not regulated by phosphorylation/dephosporylation
additional information
-
not regulated by phosphorylation/dephosporylation
additional information
-
not regulated by phosphorylation/dephosporylation
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with phosphonolactylthiamine diphosphate as structural and electrostatic analogue of alpha-lactylthiamin diphosphate. Presence of phosphonolactylthiamin diphosphate causes large conformational changes
-
preparation of catalytic subunit E1 of pyruvate dehydrogenase complex, without cofactors thiamine diphosphate and Mg2+, no evidence of disorder/order loop transformations. Comparison with holo-E1 enzyme and in an inhibitor complex with thiamine 2-thiazolone diphosphate
-
purified enzyme E1 in complex with inhibitor thiamine thiazolone diphosphate and Mg2+, sitting drop vapour diffusion method, reservoir solution: 15-20% PEG 2000 monomethyl ether, 5-10% 2-propanol, 0.2% NaN3, 100 mM HEPES, pH 7.00, 22C, 4 weeks, X-ray diffraction structure determination and analysis at 2.09 A resolution, comparison with structure determined with bound cofactor thiamine diphosphate
P0AFG8
purified recombinant pyruvate dehydrogenase multienzyme complex component E1, sitting drop vapor diffusion method, mixing of equal amounts of protein and precipitant solution of 0.006-0.01 ml, the latter containing 15-20% PEG2000 monomethyl ether, 10% propanol, 0.2% NaN3, and 60 mM HEPES, pH 7.1, 22C, 2-5 weeks, native and selenomethionine crystals, X-ray diffraction structure determination and analysis at 1.85 A resolution
P0AFG8
sitting drop vapour diffusion method with 15-20% PEG2000 monomethyl ether, 10% propanol, 0.2% NaN3 in 60 mM HEPES buffer (pH 7.05)
-
recombinant enzyme, orthorhombic crystals in polyethylene glycol 3350 by vapor-diffusion method, space group P222
-
vapour diffusion method with 14-18% PEG 3350, 0.1 mM sodium azide, and 200 mM NaSCN in 50 mM potassium phosphate (pH 8.0)
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0 - 40
-
rapid decline of activity
348944
50
-
irreversible inactivation
348925
51
-
1 min, complete inactivation
348974
60
-
pyruvate dehydrogenase complex, no loss of activity after 50 min
348986
70
-
heating the partially purified complex for 5 min inactivates pyruvate dehydrogenase component completely
348962
72
-
pyruvate dehydrogenase, complete loss of activity
348986
84
-
pyruvate dehydrogenase
348986
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
very sensitive to freezing and thawing
-
very sensitive to proteolysis, especially during purification
-
very sensitive to freezing and thawing
-
very sensitive to freezing and thawing
-
very sensitive to proteolysis, especially during purification
-
very sensitive to freezing and thawing
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
pyruvate dehydrogenase activity decreases by 88% after H2O2 treatment (2.5 mM for 30 min)
-
711033
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
liquid N2, 50 mM potassium phosphate buffer, pH 7.0, 1 mM EDTA, 0.05 mM phenylmethanesulfonylfluoride, 20-40 mg/ml protein
-
-50C, 50 mM potassium phosphate buffer, pH 7.0, 1 mM MgCl2, 20 mM thiamine diphosphate, 0.1 mM EDTA, 0.4 mM DTT, 0.1 mM NAD+, several months
-
-20C, N2-atmosphere, addition of sulfhydryl compounds, several weeks
-
-50C, 50 mM potassium phosphate buffer, pH 7.2, 10% glycerol, 1 mM DTT, several months
-
-20C, 30 mM potassium phosphate buffer, pH 7.0, 2.0-2.5 mM EDTA
-
-20C, 50 mM phosphate buffer, pH 7.0, several months, no loss of activity
-
-15C, 50 mM potassium phosphate buffer, pH 7.0, 2 mM EDTA, 0.15 mM phenylmethanesulfonylfluoride, 0.2 g/l NaN3, several months
-
-20C, 2 weeks, 10-20% loss of activity
-
-20C, presence of 50% glycerol, 10-20 mM beta-mercaptoethanol, stable for months
-
-20C, 30 mM potassium phosphate buffer, pH 7.0, 2.0-2.5 mM EDTA
-
-20C, 50 mM glycyl-glycine buffer, pH 8.0, 2 mM MgCl2, 2 mM DTT, 1-2 weeks
-
-18C, 50 mM potassium phosphate, pH 7.0, 0.5 mM EDTA, several months, no loss of activity
-
-20C, 50 mM glycyl-glycine buffer, pH 8.0, 2 mM MgCl2, 2 mM DTT, 1-2 weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase complex from ox heart, by PEG fractionation, ultracentrifugation, and gel filtration
-
pyruvate dehydrogenase purified from complex by gel filtration
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
Ni2+-Sepharose column chromatography
-
TSK DEAE-5PW HPLC column chromatography
-
alpha and beta subunits purified from enzyme complex after gel filtration in the presence of 2 M KI followed by chromatography on hydroxyapatite in the presence of 8 M urea; pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
alpha and beta subunits purified from enzyme complex by gel filtration
-
recombinant multienzyme complex components from Escherichia coli strain BL21(DE3) to homogeneity
-
recombinant wild-type E1alpha and E1beta subunits of the pyruvate decarboxylate component and mutants from Escherichia coli strain BL21(DE3)
-
pyruvate dehydrogenase complex, composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
Hansenula miso
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
Hansenula sp.
-
Ni-NTA column chromatography
-
recombinant alpha and beta subunits and recombinant alpha2,beta2 tetramer
-
; pyruvate dehydrogenase complex composed of EC 1.2. 4.1, EC 2.3.1.12, EC 1.8.1.4
Pigeon
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
isolation of EC 1.2.4.1 after elastase treatment of the complex and gel filtration
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase complex, composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
P52903
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
pyruvate dehydrogenase can be resolved from complex by incubation with 8 M urea, 4 M guanidinium chloride, 100 mM glycine/NaOH, pH 9.0 followed by gel filtration
-
pyruvate dehydrogenase complex composed of EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4
-
recombinant enzyme both expressed in Escherichia coli and Haloferax volcanii
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli strain BW25113
-
gene iar4, wild-type sequencing and chromosomal mapping to a 45 kb region 35 cM from the top of chromosome 1 between the markers F3I6.8 and F3I6.17, DNA sequence determination of iar4-1 mutant
-
expression of wild-type pyruvate dehydrogenase and N-terminal deletion mutant E1pDelta48 in Escherichia coli
-
expressed in Escherichia coli strain JRG 3456
-
expression system
-
alpha-subunit; beta-subunit
-
coexpression of the multienzyme complex components in Escherichia coli strain BL21(DE3)
-
expression of wild-type E1alpha and E1beta subunits of the pyruvate decarboxylate component and mutants in Escherichia coli strain BL21(DE3)
-
alpha-subunit
-
beta-subunit
-
co-expression of alpha subunit with human liver beta subunit in Escherichia coli; expression of alpha and beta subunits in Escherichia coli
-
expressed in Escherichia coli BL21 cells
-
expressed in Escherichia coli M15 cells
-
His-tagged alpha and beta subunits and alpha2,beta2 tetramer, expression in Escherichia coli
-
co-expression of alpha subunit with human liver beta subunit in Escherichia coli; expression of alpha and beta subunits in Escherichia coli
-
expressed in Escherichia coli BL21+ cells
Q1KSF0
expressed in Hansenula polymorpha strain DL1-L
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
PDHE1alpha1 protein and phosphorylation level decrease significantly ipsilateral to controlled cortical impact and contralateral to controlled cortical impact at 4 h, 24 h, 3- and 7-day post-controlled cortical impact, respectively
-
the activity of pyruvate dehydrogenase is reduced in diabetic rats. Thiamine ameliorates diabetes-induced PDH inhibition by suppressing the increased expression of the O-glycosylated protein
-
high glucose loads do not alter the level of PDH mRNA expressions in cardiac fibroblasts
-
the O-glycosylated PDH protein is markedly increased in cardiac fibroblasts exposed to high glucose
-
there is a moderate increase of PDHE1alpha1 mRNA in ipsilateral CCI and contralateral controlled cortical impact (1.2-1.6fold) at 4 h and 24 h post-controlled cortical impact. PDHE1alpha1 mRNA increases moderately (1.4fold) in the craniotomy group at 4 h, 24 h and 7-day post-surgery
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D15A
-
site-directed mutagenesis, 0.19% remaining activity with NAD+ and 16% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
D549A
-
in the mutant, binding and reductive acetylation of E2p lipoyl domains are highly impaired
D7A
-
site-directed mutagenesis, 0.14% remaining activity with NAD+ and 63% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
D9A
-
site-directed mutagenesis, inactive with NAD+, 80% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
E12D
-
site-directed mutagenesis, 2.3% remaining activity with NAD+ and 90% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
E12Q
-
site-directed mutagenesis, 3.3% remaining activity with NAD+ and 59% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
E401A
-
9.56% of overall wild type activity and 23.4% of wild type activity with 2,6-dichloroindolphenol
E401K
-
1.04% of overall wild type activity and 4.63% of wild type activity with 2,6-dichloroindolphenol
E401K
-
in the mutant, binding and reductive acetylation of E2p lipoyl domains are highly impaired
E410K
-
CC-bond formation is dramatically slowed down (10-fold compared with E1ec) in E401K, the loop dynamics apparently greatly influences covalent addition of substrate to the enzyme-bound thiamine diphosphate
H407A
-
crystallization data. Interaction between H407 and phosphonolactylthiamine diphosphate is essential for stabilization of two loop regions in the active site
H407A
-
0.15% of overall wild type activity and 12.0% of wild type activity with 2,6-dichloroindolphenol
H407A
-
in the mutant, binding and reductive acetylation of E2p lipoyl domains are highly impaired
I11A
-
site-directed mutagenesis, 94% remaining activity with NAD+ and E1 activity with 2,6-dichlorophenolindophenol as electron acceptor is like the wild-type E1 activity
K403A
-
11.6% of overall wild type activity and 98.0% of wild type activity with 2,6-dichloroindolphenol
K403E
-
0.56% of overall wild type activity and 5.46% of wild type activity with 2,6-dichloroindolphenol
K410A
-
23.0% of overall wild type activity and 31.6% of wild type activity with 2,6-dichloroindolphenol
K410E
-
3.7% of overall wild type activity and 26.1% of wild type activity with 2,6-dichloroindolphenol
K411A
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68.2% of overall wild type activity and 77.5% of wild type activity with 2,6-dichloroindolphenol
N404A
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1.81% of overall wild type activity and 45.1% of wild type activity with 2,6-dichloroindolphenol
P10A
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site-directed mutagenesis, unaltered activity with NAD+ and 50% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
Q408A
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31.5% of overall wild type activity and 112.1% of wild type activity with 2,6-dichloroindolphenol
R14A
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site-directed mutagenesis, 0.25% remaining activity with NAD+ as electron acceptor, E1 activity with 2,6-dichlorophenolindophenol is like the wild-type E1 activity
T13A
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site-directed mutagenesis, 13% remaining activity with NAD+ and 26% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
Y177A
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11% of wild-type activity in enzyme complex
Y177A
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in the mutant, binding and reductive acetylation of E2p lipoyl domains are highly impaired
Y177F
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7% of wild-type activity in enzyme complex
D276A
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site-directed mutagenesis, reduced activity with pyruvate compared to the wild-type enzyme
R267A
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site-directed mutagenesis, highly reduced activity with pyruvate compared to the wild-type enzyme
R282A
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site-directed mutagenesis, reduced activity with pyruvate compared to the wild-type enzyme
S283C
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site-directed mutagenesis, reduced activity with pyruvate compared to the wild-type enzyme
Y281A
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site-directed mutagenesis, reduced activity with pyruvate compared to the wild-type enzyme
Y281A/R282A
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site-directed mutagenesis, highly reduced activity with pyruvate compared to the wild-type enzyme
Y281A/R282A/S283A
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site-directed mutagenesis, highly reduced activity with pyruvate compared to the wild-type enzyme
Y281S/R282S
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site-directed mutagenesis, highly reduced activity with pyruvate compared to the wild-type enzyme
D289A
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the beta subunit mutant does not have any detectable activity in assays with NAD+ and shows no change in activity in 2,6-dichlorophenolindophenol assays
D289A
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the mutant does not have any detectable activity in PDC assay while its activity in thedecarboxylation reaction measured by 2,6-dichlorophenolindophenol assay does not significantly change
D289N
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the beta subunit mutant shows by 36% reduced activity in assays with NAD+
D289N
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the mutant does not demonstrate any change in the 2,6-dichlorophenolindophenol assay but its activity is reduced to 67% in PDC assay
E229A
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the beta subunit mutant does not show drastic changes compared to the wild type E1 activities
E229A
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the mutant does not show any significant changes compared with the wild type subunit E1 activity
E229Q
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the beta subunit mutant does not show drastic changes compared to the wild type E1 activities
E229Q
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the mutant does not show any significant changes compared with the wild type subunit E1 activity
E232A
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the beta subunit mutant does not show drastic changes compared to the wild type E1 activities
E232A
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the mutant does not show any significant changes compared with the wild type subunit E1 activity
E232Q
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the beta subunit mutant does not show drastic changes compared to the wild type E1 activities
E232Q
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the mutant does not show any significant changes compared with the wild type subunit E1 activity
E234A
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the beta subunit mutant does not show drastic changes compared to the wild type E1 activities
E234A
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the mutant does not show any significant changes compared with the wild type subunit E1 activity
E234Q
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the beta subunit mutant does not show drastic changes compared to the wild type E1 activities
E234Q
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the mutant does not show any significant changes compared with the wild type subunit E1 activity
H63A
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about 17% residual activity in assay using 2,6-dichlorophenolindophenol, only modest inhibition by acetylphosphinate and acetylmethylphosphinate
I329A
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shows 37-43% reduction in activity compared to the wild type enzyme
I329A
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the mutant shows reductions in activities in both the 2,6-dichlorophenolindophenol and PDC assays
I329del
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the mutant shows reductions in activities in both the 2,6-dichlorophenolindophenol and PDC assays
Q206L
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the mutant shows decreased PDH activity in fibroblasts, around 52% of mean control
R253G
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the mutation is associated with low PDHc activity and absence of subunit alpha of pyruvate dehydrogenase E1
S203A
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isoform PDH2, mutation of phosphorylation site
S203A/S271A
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phosphorylation at remaining site S264 causes 96% inactivation
S203A/S64A
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phosphorylation at remaining site S271 causes complete inactivation
S203E
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isoform PDH2, mutation of phosphorylation site
S264A
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isoform PDH2, mutation of phosphorylation site, no enzymic activity
S264E
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isoform PDH2, mutation of phosphorylation site
S264E
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pseudophosphorylation mutant, the preceding binding of substrate to the enzyme's active site via the substrate channel and the subsequent reductive acetylation of the E2 component are severely slowed in the mutant enzyme
S264Q
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selectively deficient in pyruvate binding and reductive acetylation of component E2
S271A
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isoform PDH2, mutation of phosphorylation site, no enzymic activity
S271E
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isoform PDH2, mutation of phosphorylation site
S64A/S271A
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phosphorylation at remaining site S203 causes 91% inactivation
I472A
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chimera between pyruvate dehydrogenase and benzoylformate dehydrogenase, increased substrate range compared to wild-type. Also catalyzes carboligation of benzaldehyde with C4, C5, C6 aliphatic 2-ketoacids
I472A/I476F
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chimera between pyruvate dehydrogenase and benzoylformate dehydrogenase, increased substrate range compared to wild-type
I476F
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chimera between pyruvate dehydrogenase and benzoylformate dehydrogenase, increased substrate range compared to wild-type
additional information
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construction of the iar4-1 mutant, defective in gene iar4 encoding the enzyme E1, by ethylmethane sulfonate, the mutant is less sensitive to a synthetic auxin and low concentrations of an ethylene precursor, but responds to free indole-3-acetic acid and other hormones in a way similar to the wild-type, the Krebs cycle and glycolysis are unaffected
additional information
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genes bvPDH_E1alpha-2 and bvPDH_E1alpha-1 encode the type 2 and type 1 variants of the E1alpha subunit of pyruvate dehydrogenase, expression as GFP-fusion protein, antisense expression, using a tapetum-specific TA29 promotor in antisense orientation, of gene type 1 variant of the E1alpha subunit via infection with Agrobacterium tumefaciens to form transgenic tobacco plants, cv. SR-1, leads to decreased transcript and male sterility, abnormal anther phenotype, poorly formed microspores, overview
additional information
Q8NNF6
enzyme-deficient mutant. Inactivation of enzyme gene leads to the inability to grow on glucose and the absence of enzymic and enzyme complex activities
K411E
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38.0% of overall wild type activity and 88.0% of wild type activity with 2,6-dichloroindolphenol
additional information
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construction of several N-terminal E1 deletion mutants by tryptic or chymotryptic digest all showing reduced enzyme activity
F266A
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site-directed mutagenesis, reduced activity with pyruvate compared to the wild-type enzyme
additional information
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mutational analysis of key amino acid residues responsible for enzyme component assembly to the multienzyme complex using E3 component mutants, overview
M153V
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the mutant shows decreased PDH activity in fibroblasts, around 30% of mean control
additional information
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mutant I329DELTA (deletion at the C-terminal of E1) shows 62% reduction in activity compared to the wild type enzyme
additional information
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the in-frame deletion mutant G143del and the 65 bp duplication mutant c.900-6_958dup65 show decreased PDH activity in fibroblasts, around 16% of mean control
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
reconstitution of pyruvate dehydrogenase complex
-
reconstitution of pyruvate dehydrogenase complex
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no reconstitution of whole complex, pyruvate dehydrogenase subunit regains some activity after separation from complex in the presence of chaperonins and ATP/MgCl2
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reconstitution of pyruvate dehydrogenase complex
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reconstitution of pyruvate dehydrogenase complex
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reconstitution of pyruvate dehydrogenase complex
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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enzyme/pyruvate dehydrogenase kinase dependent pathway is repressed in 73% of non-small cell lung carcinomas, which may be a key reason for hypoxia-inducible factor 1alpha stabilization and aerobic glycolysis. About half of enzyme-deficient carcinomas are not able to switch on the hypoxia-inducible factor 1alpha pathway, patients with these tumours have an excellent postoperative outcome. In contrast to cancer cells, fibroblasts in the tumour-supporting stroma exhibit an intense enzyme but reduced pyruvate dehydrogenase kinase 1 expression favoring maximum enzyme activity
biotechnology
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overexpression of enzyme in Lactococcus lactis results in up to eightfold increase in acetaldehyde concentration. However, the observed ethanol concentrations are similar to that of wild-type strain
biotechnology
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active expression of enzyme from non-halophilic Zymomonas mobilis in the haloarchaeon Haloferax volcanii with no difference in the secondary structure. Post-transcriptional mechanisms in the stationary phase appear to limit the amount of recombinant protein expressed