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Literature summary for 2.7.11.2 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
Search for more literature for 2.7.11.2

Activating Compound

Activating Compound Comment Organism Structure
acetyl-CoA
-
 Rattus norvegicus
acetyl-CoA isozyme PDK2: addition of K+ and Cl- required, phosphate increases the stimulating effect Mammalia
acetyl-CoA synergism with NADH Mammalia
acetyl-CoA synergism with NADH Homo sapiens
acetyl-CoA synergism with NADH Bos taurus
dibutyryl cAMP in muscle, reversed by insulin Rattus norvegicus
dihydrolipoyl transacetylase
-
 Bos taurus
dihydrolipoyl transacetylase degree of interaction and mechanism differ for the 4 different isozymes Mammalia
dihydrolipoyl transacetylase degree of interaction and mechanism differ for the 4 different isozymes Homo sapiens
dihydrolipoyl transacetylase degree of interaction and mechanism differ for the 4 different isozymes Rattus norvegicus
dihydrolipoyl transacetylase acts as a direct allosteric agent in altering the regulatory kinase activity, serves as an anchoring scaffold Mammalia
Lipid in muscle, reversed by insulin Rattus norvegicus
additional information
-
 Rattus norvegicus
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
NADH
-
 Homo sapiens
NADH
-
 Rattus norvegicus
NADH
-
 Bos taurus
NADH isozyme PDK2: addition of K+ and Cl- required, phosphate increases the stimulating effect Mammalia
Octanoate in muscle, reversed by insulin Rattus norvegicus
pyruvate
-
 Bos taurus
pyruvate inhibits at concentrations above 0.1 mM, activates below 0.05 mM, dependent on thiamine diphosphate Mammalia
WY-14,643 activator of peroxisome proliferator-activated receptor-alpha Rattus norvegicus
WY-14,643 in gastrocnemius muscle, specifically increases PDK4 expression Rattus norvegicus

Application

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

Cloned(Commentary)

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

Inhibitors

Inhibitors Comment Organism Structure
ADP
-
 Bos taurus
ADP synergism with pyruvate Homo sapiens
ADP isozyme PDK3: synergistic with phosphate; isozyme PDK4: K+ and dichloroacetate increase the inhibitory effect; synergism with pyruvate Mammalia
ADP synergism with pyruvate Rattus norvegicus
CoA
-
 Mammalia
Dichloroacetate
-
 Bos taurus
Dichloroacetate
-
 Homo sapiens
Dichloroacetate isozyme PDK2: ADP and K+ increase the inhibitory effect; isozyme PDK4: ADP, K+ and Cl- increase the inhibitory effect Mammalia
Dichloroacetate
-
 Rattus norvegicus
additional information
-
 Bos taurus
additional information
-
 Homo sapiens
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
NAD+
-
 Mammalia
phosphate enhances inhibition by pyruvate Mammalia
pyruvate synergism with ADP Bos taurus
pyruvate
-
 Homo sapiens
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
pyruvate
-
 Rattus norvegicus

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
 Homo sapiens
Mg2+
-
 Arabidopsis thaliana
Mg2+ requirement Mammalia
Mg2+ requirement Rattus norvegicus
Mg2+ requirement Bos taurus

Molecular Weight [Da]

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

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + [pyruvate dehydrogenase (lipoamide)] Zea mays
-
 ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
ATP + [pyruvate dehydrogenase (lipoamide)] Arabidopsis thaliana
-
 ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
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
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
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
ATP + [pyruvate dehydrogenase (lipoamide)] Mammalia catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1 ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
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
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
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
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
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

Organism UniProt Comment Textmining
Arabidopsis thaliana
-
-
-
Bos taurus
-
-
-
Homo sapiens
-
 4 different isozymes: PDK1, PDK2, PDK3, PDK4
-
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
-
Mammalia
-
 at least 4 different isozymes: PDK1, PDK2, PDK3, PDK4
-
Rattus norvegicus
-
-
-
Zea mays
-
 at least 2 isozymes
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
 Rattus norvegicus
-
brain isozymes PDK2 and PDK3 Mammalia
-
brown adipose tissue isozyme PDK2 Mammalia
-
gastrocnemius overexpression of isozyme PDK4 during starvation or diabetes, reversible by insulin Rattus norvegicus
-
heart
-
 Rattus norvegicus
-
heart
-
 Bos taurus
-
heart appearance of isozyme PDK1 is limited to the heart, isozyme PDK2 Mammalia
-
kidney
-
 Rattus norvegicus
-
kidney PDK2-like isozyme very tightly bound to dihydrolipoyl transacetylase, possibly 2 forms of isozyme PDK2 exist Bos taurus
-
kidney isozymes PDK2, PDK3 and PDK4 Mammalia
-
liver
-
 Rattus norvegicus
-
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
-
lung isozymes PDK3 and PDK4, low levels of isozyme PDK2 Mammalia
-
mammary gland lactating, isozyme PDK2 Mammalia
-
additional information isozyme PDK4 is overexpressed in many tissues during diabetes and starvation, particularly important in skeletal and heart muscle Mammalia
-
additional information tissue-specific expression, regulation mechanisms Mammalia
-
additional information tissue-specific expression, regulation mechanisms Homo sapiens
-
additional information tissue-specific expression, regulation mechanisms Rattus norvegicus
-
skeletal muscle isozyme PDK2 Mammalia
-
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
-
spleen isozyme PDK2, low level Mammalia
-
white adipose tissue isozyme PDK2 Mammalia
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Mammalia ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Homo sapiens ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Rattus norvegicus ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Bos taurus ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Zea mays ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
ATP + [pyruvate dehydrogenase (lipoamide)]
-
 Arabidopsis thaliana ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
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
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
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
ATP + [pyruvate dehydrogenase (lipoamide)] catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1 Mammalia ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
-
 ir
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
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
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
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
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

Subunits Comment Organism
?
-
 Rattus norvegicus
? x * 45066, isozyme PDK2, DNA sequence determination Homo sapiens
? x * 48391, isozyme PDK1, DNA sequence determination Homo sapiens
? x * 46230, isozyme PDK4, DNA sequence determination Homo sapiens
? x * 45883, isozyme PDK3, DNA sequence determination Homo sapiens
More subunit composition and complex structure Mammalia
More subunit composition and complex structure Bos taurus

Synonyms

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

Cofactor

Cofactor Comment Organism Structure
ATP dependent on Mammalia
ATP dependent on Homo sapiens
ATP dependent on Rattus norvegicus
ATP dependent on Bos taurus
ATP dependent on Arabidopsis thaliana

Ki Value [mM]

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