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Literature summary extracted from

  • Roche, T.E.; Hiromasa, Y.; Turkan, A.; Gong, X.; Peng, T.; Yan, X.; Kasten, S.A.; Bao, H.; Dong, J.
    Essential roles of lipoyl domains in the activated function and control of pyruvate dehydrogenase kinases and phosphatase isoform 1 (2003), Eur. J. Biochem., 270, 1050-1056.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.11.2 acetyl-CoA
-
 Rattus norvegicus
2.7.11.2 acetyl-CoA activates the enzyme, especially isozyme PDK2 Mammalia
2.7.11.2 acetyl-CoA domain-specific binding, isozymes PDK2 and PDK3 Mammalia
2.7.11.2 acetyl-CoA domain-specific binding, isozymes PDK2 and PDK3 Homo sapiens
2.7.11.2 dihydrolipoyl transacetylase domaine-specific binding, isozymes PDK2 and PDK3, the latter binding more tightly to the L2 domain Mammalia
2.7.11.2 dihydrolipoyl transacetylase degree of interaction and mechanism differ for the 4 different isozymes Rattus norvegicus
2.7.11.2 dihydrolipoyl transacetylase degree of interaction and mechanism differ for the 4 different isozymes Mammalia
2.7.11.2 dihydrolipoyl transacetylase degree of interaction and mechanism differ for the 4 different isozymes Homo sapiens
2.7.11.2 dihydrolipoyl transacetylase isozyme PDK2 can phosphorylate free pyruvate dehydrogenase complex but bound dihydrolipoyl transacetylase enhances the rate up to 5000fold Mammalia
2.7.11.2 dihydrolipoyl transacetylase binding and activation mechanism Mammalia
2.7.11.2 dihydrolipoyl transacetylase dynamic, effector-modified interactions of the regulatory isozymes with the flexibly held outer domains of the core-forming dihydrolipoyl acetyl transferase component of pyruvate dehydrogenase complex to adapt the complex activity, regulatory mechanism Rattus norvegicus
2.7.11.2 dihydrolipoyl transacetylase dynamic, effector-modified interactions of the regulatory isozymes with the flexibly held outer domains of the core-forming dihydrolipoyl acetyl transferase component of pyruvate dehydrogenase complex to adapt the complex activity, regulatory mechanism Mammalia
2.7.11.2 dihydrolipoyl transacetylase dynamic, effector-modified interactions of the regulatory isozymes with the flexibly held outer domains of the core-forming dihydrolipoyl acetyl transferase component of pyruvate dehydrogenase complex to adapt the complex activity, regulatory mechanism Homo sapiens
2.7.11.2 fatty acids leads to overexpression of isozyme PDK4 via mechanism involving peroxisome proliferator-activated receptor-alpha Mammalia
2.7.11.2 glucocorticoids leads to overexpression of isozyme PDK4 via mechanism involving peroxisome proliferator-activated receptor-alpha Mammalia
2.7.11.2 additional information starvation increases expression of isozyme PDK4 Rattus norvegicus
2.7.11.2 additional information starvation increases expression of isozyme PDK4 Mammalia
2.7.11.2 NADH
-
 Rattus norvegicus
2.7.11.2 NADH activates the enzyme, especially isozyme PDK2 Mammalia
2.7.11.2 NADH domain-specific binding, isozymes PDK2 and PDK3 Mammalia
2.7.11.2 NADH domain-specific binding, isozymes PDK2 and PDK3 Homo sapiens
3.1.3.43 Ca2+ stimulates PDP1 at micromolar concentrations Mammalia
3.1.3.43 additional information overview on interactions of Ca2+, Mg2+, spermine, and enzyme subunits Mammalia
3.1.3.43 spermine reduces Km-value for Mg2+ Mammalia

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.11.2 expression of isozyme PDK4 in Escherichia coli, unmodified and modified enzyme Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.11.2 ADP synergism with pyruvate Homo sapiens
2.7.11.2 ADP isozyme PDK2: synergistic with phosphate; synergism with pyruvate Mammalia
2.7.11.2 ADP synergism with pyruvate Rattus norvegicus
2.7.11.2 Insulin blockage of the expression of isozyme PDK4 via insulin-activated pathway Mammalia
2.7.11.2 additional information
-
 Homo sapiens
2.7.11.2 additional information isozyme PDK3 undergoes self-association in absence of dihydrolipoyl transacetylase domain L2 leading to a decrease in activity; starvation and diabetes reduce the expression of isozyme PDK2 Mammalia
2.7.11.2 phosphate isozyme PDK2, synergistically with ADP and pyruvate Mammalia
2.7.11.2 pyruvate very weak inhibition Homo sapiens
2.7.11.2 pyruvate isozyme PDK2: synergistic with phosphate; isozyme PDK3; very weak inhibition Mammalia
2.7.11.2 pyruvate very weak inhibition Rattus norvegicus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.1.12 additional information
-
 additional information
-
 Homo sapiens
2.3.1.12 additional information
-
 additional information
-
 Rattus norvegicus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.1.12 mitochondrion
-
 Homo sapiens 5739
-
2.3.1.12 mitochondrion
-
 Rattus norvegicus 5739
-
2.7.11.2 mitochondrion
-
 Rattus norvegicus 5739
-
2.7.11.2 mitochondrion
-
 Mammalia 5739
-
2.7.11.2 mitochondrion
-
 Homo sapiens 5739
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.3.1.12 Mg2+
-
 Homo sapiens
2.3.1.12 Mg2+
-
 Rattus norvegicus
3.1.3.43 Mg2+ required, Km-value of PDP1 is 2 mM in absence and 0.4 mM in presence of spermine, Km-value of PDP2 is 16 mM in absence and 3 mM in presence of spermine Mammalia

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
3.1.3.43 52000
-
 PDP1, 1 * 52000, catalytic subunit,+ 1 * 69000, regulatory subunit, overview Mammalia
3.1.3.43 69000
-
 PDP1, 1 * 52000, catalytic subunit,+ 1 * 69000, regulatory subunit, overview Mammalia

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.12 additional information Homo sapiens the enzyme mediates Ca2+-activation of isozymes 1 of pyruvate dehydrogenase phosphatase by 10fold, and enhances the accessibility of the E1 substrate for the regulatory enzymes, and mediate feedback effector control by NADH and acetyl-CoA, and modifies the allosteric control, mechanism, overview ?
-
 ?
2.3.1.12 additional information Rattus norvegicus the enzyme mediates Ca2+-activation of isozymes 1 of pyruvate dehydrogenase phosphatase by 10fold, and enhances the accessibility of the E1 substrate for the regulatory enzymes, and mediate feedback effector control by NADH and acetyl-CoA, and modifies the allosteric control, mechanism, overview ?
-
 ?
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Mammalia the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Homo sapiens the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Rattus norvegicus the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Mammalia tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Homo sapiens tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Rattus norvegicus tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Mammalia catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1 ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Homo sapiens catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1 ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Rattus norvegicus catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1 ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Rattus norvegicus high-fat feeding increases the expression of isozyme PDK2, but not of PDK4, hyperthyroidism increases the expression of both isozymes, physiological implications ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.12 Homo sapiens
-
 enzyme forms the core of the pyruvate dehydrogenase multienzyme complex
-
2.3.1.12 Rattus norvegicus
-
 enzyme forms the core of the pyruvate dehydrogenase multienzyme complex
-
2.7.11.2 Homo sapiens
-
 4 different isozymes: PDK1, PDK2, PDK3, PDK4
-
2.7.11.2 Mammalia
-
 at least 4 different isozymes: PDK1, PDK2, PDK3, PDK4
-
2.7.11.2 Rattus norvegicus
-
 4 different isozymes: PDK1, PDK2, PDK3, PDK4
-
3.1.3.43 Mammalia
-
 two isoforms
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.1.12 purification of the multienzyme complex Homo sapiens
2.3.1.12 purification of the multienzyme complex Rattus norvegicus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.1.12 heart
-
 Rattus norvegicus
-
2.3.1.12 kidney
-
 Rattus norvegicus
-
2.7.11.2 heart
-
 Rattus norvegicus
-
2.7.11.2 heart
-
 Mammalia
-
2.7.11.2 kidney
-
 Rattus norvegicus
-
2.7.11.2 kidney
-
 Mammalia
-
3.1.3.43 adipose tissue PDP2 Mammalia
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.12 additional information the enzyme mediates Ca2+-activation of isozymes 1 of pyruvate dehydrogenase phosphatase by 10fold, and enhances the accessibility of the E1 substrate for the regulatory enzymes, and mediate feedback effector control by NADH and acetyl-CoA, and modifies the allosteric control, mechanism, overview Homo sapiens ?
-
 ?
2.3.1.12 additional information the enzyme mediates Ca2+-activation of isozymes 1 of pyruvate dehydrogenase phosphatase by 10fold, and enhances the accessibility of the E1 substrate for the regulatory enzymes, and mediate feedback effector control by NADH and acetyl-CoA, and modifies the allosteric control, mechanism, overview Rattus norvegicus ?
-
 ?
2.3.1.12 additional information interactions are different with the different isoforms of the regulatory enzymes of the multienzyme complex, signal mechanism for stimulation, overview, enzyme forms the core of the pyruvate dehydrogenase multienzyme complex, the flexibly held outer domains of the enzyme show dynamic, E2 is responsible for effector-modified interactions with the complex' regulatory enzymes pyruvate dehydrogenase kinase PDK and pyruvate dehydrogenase phosphatase PDP, which exist in different isoforms, overview Homo sapiens ?
-
 ?
2.3.1.12 additional information interactions are different with the different isoforms of the regulatory enzymes of the multienzyme complex, signal mechanism for stimulation, overview, enzyme forms the core of the pyruvate dehydrogenase multienzyme complex, the flexibly held outer domains of the enzyme show dynamic, E2 is responsible for effector-modified interactions with the complex' regulatory enzymes pyruvate dehydrogenase kinase PDK and pyruvate dehydrogenase phosphatase PDP, which exist in different isoforms, overview Rattus norvegicus ?
-
 ?
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit Mammalia ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit Homo sapiens ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit Rattus norvegicus ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] isozyme PDK2 can phosphorylate free pyruvate dehydrogenase complex but bound dihydrolipoyl transacetylase enhances the rate up to 5000fold Mammalia ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex Mammalia ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex Homo sapiens ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex Rattus norvegicus ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption Mammalia ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption Homo sapiens ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption Rattus norvegicus ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1 Mammalia ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1 Homo sapiens ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1 Rattus norvegicus ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] high-fat feeding increases the expression of isozyme PDK2, but not of PDK4, hyperthyroidism increases the expression of both isozymes, physiological implications Rattus norvegicus ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir

Subunits

EC Number Subunits Comment Organism
2.3.1.12 additional information the enzyme forms the core unit E2, consisting of 4 domains in 60mer, a trimer of 3 20mers, of the pyruvate dehydrogenase multienzyme complex binding the other components, i.e. pyruvate decarboxylase and dihydrolipoyl dehydrogenase, tightly at its innerlipoyl or N-terminal lipoyl domain, respectively, composition overview Homo sapiens
2.3.1.12 additional information the enzyme forms the core unit E2, consisting of 4 domains in 60mer, a trimer of 3 20mers, of the pyruvate dehydrogenase multienzyme complex binding the other components, i.e. pyruvate decarboxylase and dihydrolipoyl dehydrogenase, tightly at its innerlipoyl or N-terminal lipoyl domain, respectively, composition overview Rattus norvegicus
3.1.3.43 heterodimer PDP1, 1 * 52000, catalytic subunit,+ 1 * 69000, regulatory subunit, overview Mammalia
3.1.3.43 additional information overview on interactions and binding of subunits Mammalia

Synonyms

EC Number Synonyms Comment Organism
2.3.1.12 dihydrolipoyl acetyl transferase
-
 Homo sapiens
2.3.1.12 dihydrolipoyl acetyl transferase
-
 Rattus norvegicus
2.3.1.12 E2
-
 Homo sapiens
2.3.1.12 additional information the enzyme forms the core unit E2 of the pyruvate dehydrogenase multienzyme complex binding the other components, i.e. pyruvate decarboxylase E1 and dihydrolipoyl dehydrogenase E3, tightly at its innerlipoyl or N-terminal lipoyl domain, respectively, composition overview Homo sapiens
2.7.11.2 PDK
-
 Rattus norvegicus
2.7.11.2 PDK
-
 Mammalia
2.7.11.2 PDK
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.11.2 ATP dependent on Rattus norvegicus
2.7.11.2 ATP dependent on Mammalia
2.7.11.2 ATP dependent on Homo sapiens