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Literature summary extracted from

  • Roche, T.E.; Baker, J.C.; Yan, X.; Hiromasa, Y.; Gong, X.; Peng, T.; Dong, J.; Turkan, A.; Kasten, S.A.
    Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms (2001), Prog. Nucleic Acid Res. Mol. Biol., 70, 33-75.
    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 isozyme PDK2: addition of K+ and Cl- required, phosphate increases the stimulating effect Mammalia
2.7.11.2 acetyl-CoA synergism with NADH Mammalia
2.7.11.2 acetyl-CoA synergism with NADH Homo sapiens
2.7.11.2 acetyl-CoA synergism with NADH Bos taurus
2.7.11.2 dibutyryl cAMP in muscle, reversed by insulin Rattus norvegicus
2.7.11.2 dihydrolipoyl transacetylase
-
 Bos taurus
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 degree of interaction and mechanism differ for the 4 different isozymes Rattus norvegicus
2.7.11.2 dihydrolipoyl transacetylase acts as a direct allosteric agent in altering the regulatory kinase activity, serves as an anchoring scaffold Mammalia
2.7.11.2 Lipid in muscle, reversed by insulin Rattus norvegicus
2.7.11.2 additional information
-
 Rattus norvegicus
2.7.11.2 additional information model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms Mammalia
2.7.11.2 NADH
-
 Homo sapiens
2.7.11.2 NADH
-
 Rattus norvegicus
2.7.11.2 NADH
-
 Bos taurus
2.7.11.2 NADH isozyme PDK2: addition of K+ and Cl- required, phosphate increases the stimulating effect Mammalia
2.7.11.2 Octanoate in muscle, reversed by insulin Rattus norvegicus
2.7.11.2 pyruvate
-
 Bos taurus
2.7.11.2 pyruvate inhibits at concentrations above 0.1 mM, activates below 0.05 mM, dependent on thiamine diphosphate Mammalia
2.7.11.2 WY-14,643 activator of peroxisome proliferator-activated receptor-alpha Rattus norvegicus
2.7.11.2 WY-14,643 in gastrocnemius muscle, specifically increases PDK4 expression Rattus norvegicus

Application

EC Number Application Comment Organism
2.7.11.2 pharmacology target for development of specific inhibitors of PDK isozymes to regulate glucose levels in the blood Mammalia

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.11.2 4 isozymes: PDK1, PDK2, PDK3, PDK4 Mammalia

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.11.2 ADP
-
 Bos taurus
2.7.11.2 ADP synergism with pyruvate Homo sapiens
2.7.11.2 ADP isozyme PDK3: synergistic with phosphate; isozyme PDK4: K+ and dichloroacetate increase the inhibitory effect; synergism with pyruvate Mammalia
2.7.11.2 ADP synergism with pyruvate Rattus norvegicus
2.7.11.2 CoA
-
 Mammalia
2.7.11.2 Dichloroacetate
-
 Bos taurus
2.7.11.2 Dichloroacetate
-
 Homo sapiens
2.7.11.2 Dichloroacetate isozyme PDK2: ADP and K+ increase the inhibitory effect; isozyme PDK4: ADP, K+ and Cl- increase the inhibitory effect Mammalia
2.7.11.2 Dichloroacetate
-
 Rattus norvegicus
2.7.11.2 additional information
-
 Bos taurus
2.7.11.2 additional information
-
 Homo sapiens
2.7.11.2 additional information model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms; the effects of mono- and divalent ions vary greatly between the isozymes Mammalia
2.7.11.2 NAD+
-
 Mammalia
2.7.11.2 phosphate enhances inhibition by pyruvate Mammalia
2.7.11.2 pyruvate synergism with ADP Bos taurus
2.7.11.2 pyruvate
-
 Homo sapiens
2.7.11.2 pyruvate inhibits at concentrations above 0.1 mM, activates below 0.05 mM; isozyme PDK2: ADP and K+ increase the inhibitory effect; isozyme PDK3; synergism with ADP Mammalia
2.7.11.2 pyruvate
-
 Rattus norvegicus

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.11.2 Mg2+
-
 Homo sapiens
2.7.11.2 Mg2+
-
 Arabidopsis thaliana
2.7.11.2 Mg2+ requirement Mammalia
2.7.11.2 Mg2+ requirement Rattus norvegicus
2.7.11.2 Mg2+ requirement Bos taurus
3.1.3.43 Ca2+ activation, overview Mammalia
3.1.3.43 Mg2+ two molecules per active site of each isoform, regulation of enzyme activity via effector-altered sensitivities to Mg2+-level Mammalia

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.7.11.2 45066
-
 x * 45066, isozyme PDK2, DNA sequence determination Homo sapiens
2.7.11.2 45883
-
 x * 45883, isozyme PDK3, DNA sequence determination Homo sapiens
2.7.11.2 46230
-
 x * 46230, isozyme PDK4, DNA sequence determination Homo sapiens
2.7.11.2 48391
-
 x * 48391, isozyme PDK1, DNA sequence determination Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Zea mays
-
 ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] Arabidopsis thaliana
-
 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)] Bos taurus 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)] Mammalia isozyme PDK3 has a putative regulatory role of the pyruvate dehydrogenase complex in sperm ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 additional information Mammalia model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.11.2 Arabidopsis thaliana
-
-
-
2.7.11.2 Bos taurus
-
-
-
2.7.11.2 Homo sapiens
-
 4 different isozymes: PDK1, PDK2, PDK3, PDK4
-
2.7.11.2 Homo sapiens
-
 isozyme development via gene duplication, gene locations are: PDK1 in chromosome 2, PDK2 in chromosome 17, PDK3 in chromosome Xp22, PDK4 in chromosome 7q21q22
-
2.7.11.2 Mammalia
-
 at least 4 different isozymes: PDK1, PDK2, PDK3, PDK4
-
2.7.11.2 Rattus norvegicus
-
-
-
2.7.11.2 Zea mays
-
 at least 2 isozymes
-
3.1.3.43 Mammalia
-
 two isoforms
-

Reaction

EC Number Reaction Comment Organism Reaction ID
3.1.3.43 [pyruvate dehydrogenase (acetyl-transferring)] phosphate + H2O = [pyruvate dehydrogenase (acetyl-transferring)] + phosphate overview on mechanism and regulation of enzyme Mammalia
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.11.2 brain
-
 Rattus norvegicus
-
2.7.11.2 brain isozymes PDK2 and PDK3 Mammalia
-
2.7.11.2 brown adipose tissue isozyme PDK2 Mammalia
-
2.7.11.2 gastrocnemius overexpression of isozyme PDK4 during starvation or diabetes, reversible by insulin Rattus norvegicus
-
2.7.11.2 heart
-
 Rattus norvegicus
-
2.7.11.2 heart
-
 Bos taurus
-
2.7.11.2 heart appearance of isozyme PDK1 is limited to the heart, isozyme PDK2 Mammalia
-
2.7.11.2 kidney
-
 Rattus norvegicus
-
2.7.11.2 kidney PDK2-like isozyme very tightly bound to dihydrolipoyl transacetylase, possibly 2 forms of isozyme PDK2 exist Bos taurus
-
2.7.11.2 kidney isozymes PDK2, PDK3 and PDK4 Mammalia
-
2.7.11.2 liver
-
 Rattus norvegicus
-
2.7.11.2 liver isozymes PDK2 and PDK4 are both overexpressed under conditions of starvation, diabetes, or high-fat feeding, low-carbohydrate diet, or due to artificially elevated cAMP or 3,5,3'-triidothyronine levels, reversible by insulin or high-carbohydrate diet Mammalia
-
2.7.11.2 lung isozymes PDK3 and PDK4, low levels of isozyme PDK2 Mammalia
-
2.7.11.2 mammary gland lactating, isozyme PDK2 Mammalia
-
2.7.11.2 additional information isozyme PDK4 is overexpressed in many tissues during diabetes and starvation, particularly important in skeletal and heart muscle Mammalia
-
2.7.11.2 additional information tissue-specific expression, regulation mechanisms Mammalia
-
2.7.11.2 additional information tissue-specific expression, regulation mechanisms Homo sapiens
-
2.7.11.2 additional information tissue-specific expression, regulation mechanisms Rattus norvegicus
-
2.7.11.2 skeletal muscle isozyme PDK2 Mammalia
-
2.7.11.2 sperm isozyme PDK3 with unique E1 subunit probably encoded on the Y-chromosome in contrary to the normal E1 subunit which is encoded on the X-chromosome, regulatory role Mammalia
-
2.7.11.2 spleen isozyme PDK2, low level Mammalia
-
2.7.11.2 white adipose tissue isozyme PDK2 Mammalia
-
3.1.3.43 adipose tissue PDP2, probably target for insulin activation Mammalia
-
3.1.3.43 brain PDP1 Mammalia
-
3.1.3.43 heart PDP1 Mammalia
-
3.1.3.43 kidney PDP1 Mammalia
-
3.1.3.43 liver PDP1, PDP2 Mammalia
-
3.1.3.43 skeletal muscle PDP1 Mammalia
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Mammalia ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Homo sapiens ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Rattus norvegicus ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Bos taurus ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Zea mays ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Arabidopsis thaliana 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)] catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1 Bos taurus ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 ATP + [pyruvate dehydrogenase (lipoamide)] isozyme PDK3 has a putative regulatory role of the pyruvate dehydrogenase complex in sperm Mammalia ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
2.7.11.2 additional information model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms Mammalia ?
-
 ?

Subunits

EC Number Subunits Comment Organism
2.7.11.2 ?
-
 Rattus norvegicus
2.7.11.2 ? x * 45066, isozyme PDK2, DNA sequence determination Homo sapiens
2.7.11.2 ? x * 48391, isozyme PDK1, DNA sequence determination Homo sapiens
2.7.11.2 ? x * 46230, isozyme PDK4, DNA sequence determination Homo sapiens
2.7.11.2 ? x * 45883, isozyme PDK3, DNA sequence determination Homo sapiens
2.7.11.2 More subunit composition and complex structure Mammalia
2.7.11.2 More subunit composition and complex structure Bos taurus
3.1.3.43 heterodimer isoform PDP1, composed of catalytic subunit PDP1c and regulatory subunit PDP1r of 96000 Da, overview Mammalia

Synonyms

EC Number Synonyms Comment Organism
2.7.11.2 More
-
 Rattus norvegicus
2.7.11.2 More PDK isozymes and the related branched-chain dehydrogenase kinase form a unique family of serine kinases Mammalia
2.7.11.2 More PDK isozymes and the related branched-chain dehydrogenase kinase form a unique family of serine kinases Homo sapiens
2.7.11.2 PDK
-
 Mammalia
2.7.11.2 PDK
-
 Homo sapiens
2.7.11.2 PDK
-
 Rattus norvegicus
2.7.11.2 PDK
-
 Bos taurus

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.11.2 ATP dependent on Mammalia
2.7.11.2 ATP dependent on Homo sapiens
2.7.11.2 ATP dependent on Rattus norvegicus
2.7.11.2 ATP dependent on Bos taurus
2.7.11.2 ATP dependent on Arabidopsis thaliana
3.1.3.43 FAD noncovalently bound to PDP1r Mammalia

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.7.11.2 additional information
-
 additional information
-
 Bos taurus
2.7.11.2 additional information
-
 additional information isozyme PDK4: K+ reduces the Ki for ADP and therefor enhances the inhibitory affect Mammalia