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Literature summary for 2.7.11.2 extracted from

  • Roche, T.E.; Hiromasa, Y.
    Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer (2007), Cell. Mol. Life Sci., 64, 830-849.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
acetyl-CoA stimulation by acetyl-CoA requires both K+ and at least one anion, phosphate or chloride, mechanisms for stimulation of PDK2, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overview Homo sapiens
acetyl-CoA stimulation by acetyl-CoA requires both K+ and at least one anion, phosphate or chloride, mechanisms for stimulation of PDK2, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overview Rattus norvegicus
NADH stimulation by NADH requires both K+ and at least one anion, phosphate or chloride, mechanisms for stimulation of PDK2, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overview Homo sapiens
NADH stimulation by NADH requires both K+ and at least one anion, phosphate or chloride, mechanisms for stimulation of PDK2, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overview Rattus norvegicus

Inhibitors

Inhibitors Comment Organism Structure
ADP
-
Homo sapiens
ADP
-
Rattus norvegicus
AZD7545 an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor Homo sapiens
AZD7545 an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor Rattus norvegicus
compound K an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor Homo sapiens
compound K an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor Rattus norvegicus
additional information PDK2 inhibition mechanism, overview Homo sapiens
additional information PDK2 inhibition mechanism, overview Rattus norvegicus
Nov3r an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor, a mimic of the acetyl-dihydrolipoyl group, inhibits PDK2 Homo sapiens
Nov3r an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor, a mimic of the acetyl-dihydrolipoyl group, inhibits PDK2 Rattus norvegicus
pyruvate
-
Homo sapiens
pyruvate
-
Rattus norvegicus

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
Homo sapiens 5739
-
mitochondrion
-
Rattus norvegicus 5739
-

Metals/Ions

Metals/Ions Comment Organism Structure
Cl- activates Homo sapiens
Cl- activates Rattus norvegicus
K+ activates, the Km for ATP is decreased and ADP inhibition is enhanced by elevating K+ ion levels, ligand-induced changes in K+ binding, overview Homo sapiens
K+ activates, the Km for ATP is decreased and ADP inhibition is enhanced by elevating K+ ion levels, ligand-induced changes in K+ binding, overview Rattus norvegicus
Mg2+ activates Homo sapiens
Mg2+ activates Rattus norvegicus
phosphate activates Homo sapiens
phosphate activates Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate, regulation of the pyruvate dehydrogenase complex, PDK4 overexpression in association with type I diabetes ?
-
?
additional information Rattus norvegicus PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate, regulation of the pyruvate dehydrogenase complex, PDK4 overexpression in association with type I diabetes ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Rattus norvegicus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
adipose tissue mainly isozyme PDK2 Homo sapiens
-
adipose tissue mainly isozyme PDK2 Rattus norvegicus
-
heart
-
Homo sapiens
-
heart
-
Rattus norvegicus
-
liver isozymes PDK2 and PDK4 Homo sapiens
-
liver isozymes PDK2 and PDK4, obese Zucker rats show levels of expression of PDK2 and PDK4 in liver and skeletal muscle similar to those found in lean rats Rattus norvegicus
-
skeletal muscle isozymes PDK2 and PDK4 Homo sapiens
-
skeletal muscle isozymes PDK2 and PDK4, obese Zucker rats show levels of expression of PDK2 and PDK4 in liver and skeletal muscle similar to those found in lean rats Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate, regulation of the pyruvate dehydrogenase complex, PDK4 overexpression in association with type I diabetes Homo sapiens ?
-
?
additional information PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate, regulation of the pyruvate dehydrogenase complex, PDK4 overexpression in association with type I diabetes Rattus norvegicus ?
-
?
additional information PD kinase isozymes PDK1, PDK2, PDK3 and PDK4, reduce the active form of pyruvate dehydrogenase complex, PDC, via binding to the inner lipoyl domain L2 of the dihydrolipoyl acetyltransferase E2, PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal regulatory domain, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overall reaction of the pyruvate dehydrogenase complex, overview Homo sapiens ?
-
?
additional information PD kinase isozymes PDK1, PDK2, PDK3 and PDK4, reduce the active form of pyruvate dehydrogenase complex, PDC, via binding to the inner lipoyl domain L2 of the dihydrolipoyl acetyltransferase E2, PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal regulatory domain, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overall reaction of the pyruvate dehydrogenase complex, overview Rattus norvegicus ?
-
?

Subunits

Subunits Comment Organism
More components and organization of the mammalian pyruvate dehydrogenase complex, including the enzyme Homo sapiens
More components and organization of the mammalian pyruvate dehydrogenase complex, including the enzyme Rattus norvegicus

Synonyms

Synonyms Comment Organism
PDK2
-
Homo sapiens
PDK2
-
Rattus norvegicus
PDK4
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens
ATP
-
Rattus norvegicus