Any feedback?
Information on EC 1.2.1.104 - pyruvate dehydrogenase system
for references in articles please use BRENDA:EC1.2.1.104Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.2.1.104 pyruvate dehydrogenase systemIUBMB Comments
The pyruvate dehydrogenase system (PDH) is a large enzyme complex that belongs to the 2-oxoacid dehydrogenase system family, which also includes EC 1.2.1.25, branched-chain alpha-keto acid dehydrogenase system, EC 1.2.1.105, 2-oxoglutarate dehydrogenase system, EC 1.4.1.27, glycine cleavage system, and EC 2.3.1.190, acetoin dehydrogenase system. With the exception of the glycine cleavage system, which contains 4 components, the 2-oxoacid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxoacid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and a dihydrolipoamide dehydrogenase (E3). The reaction catalysed by this system is the sum of three activities: EC 1.2.4.1, pyruvate dehydrogenase (acetyl-transferring) (E1), EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase (E2), and EC 1.8.1.4, dihydrolipoyl dehydrogenase (E3). The mammalian system also includes E3 binding protein, which is involved in the interaction between the E2 and E3 subunits.
Specify your search results
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
+
=
+
+
=
+
Synonyms
pdh complex, pyruvate dehydrogenase system, mrp-3, pdhe1alpha1, pyruvate dehydrogenase alpha subunit, dihydrolipoyllysine-residue acetyltransferase component, plastidial pyruvate dehydrogenase complex, e1 component of pyruvate dehydrogenase complex, pdh-e1 catalytic subunit, pdhalpha, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aceE
AceF
dihydrolipoyllysine-residue acetyltransferase component
DLD
E1 component of pyruvate dehydrogenase complex
E1 component subunit alpha
Mrp-3
Pda1
Pda1p
PDC
PDH
PDH complex
PDHa
PdhA1
PdhB1
pyruvate dehydrogenase complex
additional information
-
component of the pyruvate dehydrogenase multienzyme complex
dihydrolipoyllysine-residue acetyltransferase component
cf. EC 2.3.1.12
dihydrolipoyllysine-residue acetyltransferase component
cf. EC 2.3.1.12
-
PDH
-
-
-
-
pyruvate dehydrogenase complex
-
-
-
-
pyruvate dehydrogenase complex
-
the complex displays two distinct enzymatic activities: pyruvate dehydrogenase and tellurite reductase
pyruvate dehydrogenase complex
-
the complex displays two distinct enzymatic activities: pyruvate dehydrogenase and tellurite reductase
-
pyruvate dehydrogenase complex
-
multienzyme complex composed of three catalytic components (pyruvate dehydrogenase, dihydrolipoamide acetyltransferase, and dihydrolipoamide dehydrogenase), one binding protein (dihydrolipoamide dehydrogenase-binding protein), and two regulatory enzymes (a family of pyruvate dehydrogenase kinases and a family of pyruvate dehydrogenase phosphatases)
pyruvate dehydrogenase complex
-
enzyme in complex with alpha-ketoglutarate dehydrogenase
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
pyruvate + CoA + NAD+ = acetyl-CoA + CO2 + NADH
-
-
-
-
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
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
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
BRENDA
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
pyruvate:NAD+ 2-oxidoreductase (CoA-acetylating)
The pyruvate dehydrogenase system (PDH) is a large enzyme complex that belongs to the 2-oxoacid dehydrogenase system family, which also includes EC 1.2.1.25, branched-chain alpha-keto acid dehydrogenase system, EC 1.2.1.105, 2-oxoglutarate dehydrogenase system, EC 1.4.1.27, glycine cleavage system, and EC 2.3.1.190, acetoin dehydrogenase system. With the exception of the glycine cleavage system, which contains 4 components, the 2-oxoacid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxoacid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and a dihydrolipoamide dehydrogenase (E3). The reaction catalysed by this system is the sum of three activities: EC 1.2.4.1, pyruvate dehydrogenase (acetyl-transferring) (E1), EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase (E2), and EC 1.8.1.4, dihydrolipoyl dehydrogenase (E3). The mammalian system also includes E3 binding protein, which is involved in the interaction between the E2 and E3 subunits.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
hydroxyethyl thiamine diphosphate + CoA + NAD+
? + NADH
-
-
-
-
?
pyruvate + CoA + dichlorophenol indophenol
acetyl-CoA + CO2 + ?
-
-
-
?
pyruvate + CoA + ferricyanide
acetyl-CoA + CO2 + ferrocyanide
-
-
-
?
pyruvate + CoA + oxidized 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + reduced 2,6-dichlorophenolindophenol
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine
[dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
-
-
-
-
?
pyruvate + CoA + oxidized 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + reduced 2,6-dichlorophenolindophenol
-
-
-
-
?
pyruvate + CoA + oxidized 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + reduced 2,6-dichlorophenolindophenol
-
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
Hansenula miso
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
Hansenula miso
-
low reactivity with 2-ketovalerate
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
Hansenula miso
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
additional information
?
-
non-complex-bound E1p shows the same cooperativity as found for complex-bound E1p. A Hill coefficient of 1.2-1.6 is calculated for non-complex bound E1p
-
-
-
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
?
-
-
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 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
?
-
-
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 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
?
-
pyruvate is a better substrate than 2-oxobutanoate, other 2-oxo-acids are not substrates
-
-
-
additional information
?
-
-
substrate interaction kinetics for all substrates are consistent with a multisite ping-pong mechanism
-
-
-
additional information
?
-
-
pyruvate-supported mitochondrial respiration state 3
-
-
?
additional information
?
-
-
substrate interaction kinetics for all substrates are consistent with a multisite ping-pong mechanism
-
-
-
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
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
-
-
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
Hansenula miso
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
Hansenula miso
-
low reactivity with 2-ketovalerate
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
Hansenula miso
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by hydroxypyruvate
-
?
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
?
-
-
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 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
?
-
-
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
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
CoA and NAD+ required by pyruvate dehydrogenase complex
-
thiamine diphosphate
only one of the two thiamine molecules bound to the two active sites of the alpha2beta2 E1 component is in a chemically activated state exhibiting an apparent C2 ionization rate constant of approximately 50 per s at pH 7.6 and 30°C, whereas the thiamine in the inactive site ionizes with a rate that is at least 3 orders of magnitude smaller
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Mn2+
Ni2+
additional information
additional information
-
no activation by other divalent cations, except Mg2+, Mn2+, Ca2+, Ni2+
additional information
divalent cation requirement is best satisfied by Mg2+
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-(4-bromophenyl)ethanone O-((1-((4-amino-2-methylpyrimidin-5-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)oxime
thiamine diphosphate analog, at 0.1 mM 33% inhibition against Gibberlla zeae
1-(4-chlorophenyl)ethanone O-((1-((4-amino-2-methylpyrimidin-5-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)oxime
thiamine diphosphate analog, at 0.1 mM 35% inhibition against Gibberlla zeae
1-(4-nitrophenyl)ethanone O-((1-((4-amino-2-methylpyrimidin-5-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)oxime
thiamine diphosphate analog, at 0.1 mM 50% inhibition against Gibberlla zeae
1-[3-[4-(1,3,2-dithiarsinan-2-yl)anilino]-3-oxopropyl]-4-[(E)-2-(1H-indol-3-yl)ethenyl]pyridin-1-ium
i.e. PDT-PAO-16, organic arsenal inhibitor, mainly accumulates in mitochondria within hours and suppresses the activity of the pyruvate dehydrogenase complex resulting in the inhibition of ATP synthesis and thermogenesis disorder. The suppression of respiratory chain complex I and IV accelerates the mitochondrial dysfunction leading to caspase family-dependent apoptosis. In vivo, the acute promyelocytic leukemia is greatly alleviated in the PDT-PAO-F16 treated group in an acute promyelocytic leukemia mice model
2-([1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-iodo-4,5-dihydro-1H-1,2,3-triazol-4-yl]methyl)-1H-isoindole-1,3(2H)-dione
potent algaecidal activity against Synechocystis sp. PCC 6803
3-([1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4,5-dihydro-1H-1,2,3-triazol-4-yl]methyl)-5-chloroquinazolin-4(3H)-one
-
3-([1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4,5-dihydro-1H-1,2,3-triazol-4-yl]methyl)-6-bromoquinazolin-4(3H)-one
-
3-([1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-iodo-4,5-dihydro-1H-1,2,3-triazol-4-yl]methyl)-6-bromoquinazolin-4(3H)-one
potent algaecidal activity against Synechocystis sp. PCC 6803
3-([1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-iodo-4,5-dihydro-1H-1,2,3-triazol-4-yl]methyl)-6-chloro-1,2,3-benzotriazin-4(3H)-one
-
4-((1-((4-amino-2-methylpyrimidin-5-yl)methyl)-5-iodo-1H-1,2,3-triazol-4-yl)methoxy)benzonitrile
-
exhibits very good enzyme-selective inhibition of PDH-E1 between pig heart and Escherichia coli and activity against Rhizoctonia solani and Botrytis cinerea even at 12.5 lg/ml
4-aminophenyl arsenoxide
0.1 mM, 92% loss of activity in presence of pyruvate and CoA. Controls lacking pyruvate and/or coenzyme A, but containing H2NPhAsO, retain nearly all their pyruvate dehydrogenase complex activity. The arsenoxide forms a stable cyclic dithiolarsinite with reduced lipoic acid on E2 which is generated by pyruvate and coenzyme A according. Pyruvate dehydrogenase complex activity can be recovered to 78% within 2 min following the addition of 2,3-dithiopropanol