Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary 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

EC Number Activating Compound Comment Organism Structure
2.7.11.2 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
2.7.11.2 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
2.7.11.2 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
2.7.11.2 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

EC Number Inhibitors Comment Organism Structure
2.7.11.2 ADP
-
 Homo sapiens
2.7.11.2 ADP
-
 Rattus norvegicus
2.7.11.2 AZD7545 an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor Homo sapiens
2.7.11.2 AZD7545 an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor Rattus norvegicus
2.7.11.2 compound K an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor Homo sapiens
2.7.11.2 compound K an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor Rattus norvegicus
2.7.11.2 additional information PDK2 inhibition mechanism, overview Homo sapiens
2.7.11.2 additional information PDK2 inhibition mechanism, overview Rattus norvegicus
2.7.11.2 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
2.7.11.2 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
2.7.11.2 pyruvate
-
 Homo sapiens
2.7.11.2 pyruvate
-
 Rattus norvegicus

Localization

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

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.11.2 Cl- activates Homo sapiens
2.7.11.2 Cl- activates Rattus norvegicus
2.7.11.2 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
2.7.11.2 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
2.7.11.2 Mg2+ activates Homo sapiens
2.7.11.2 Mg2+ activates Rattus norvegicus
2.7.11.2 phosphate activates Homo sapiens
2.7.11.2 phosphate activates Rattus norvegicus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.11.2 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 ?
-
 ?
2.7.11.2 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

EC Number Organism UniProt Comment Textmining
2.7.11.2 Homo sapiens
-
-
-
2.7.11.2 Rattus norvegicus
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.11.2 adipose tissue mainly isozyme PDK2 Homo sapiens
-
2.7.11.2 adipose tissue mainly isozyme PDK2 Rattus norvegicus
-
2.7.11.2 heart
-
 Homo sapiens
-
2.7.11.2 heart
-
 Rattus norvegicus
-
2.7.11.2 liver isozymes PDK2 and PDK4 Homo sapiens
-
2.7.11.2 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
-
2.7.11.2 skeletal muscle isozymes PDK2 and PDK4 Homo sapiens
-
2.7.11.2 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)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.11.2 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 ?
-
 ?
2.7.11.2 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 ?
-
 ?
2.7.11.2 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 ?
-
 ?
2.7.11.2 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

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

Synonyms

EC Number Synonyms Comment Organism
2.7.11.2 PDK2
-
 Homo sapiens
2.7.11.2 PDK2
-
 Rattus norvegicus
2.7.11.2 PDK4
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.11.2 ATP
-
 Homo sapiens
2.7.11.2 ATP
-
 Rattus norvegicus