Regulation of branched-chain α-ketoacid dehydrogenase kinase

Ralph Paxton, Robert Harris

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Isolated rabbit liver branched-chain α-ketoacid dehydrogenase was inhibited in a mixed manner relative to ATP by α-ketoisocaproate, α-keto-β-methylvalerate, α-ketoisovalerate, α-ketocaproate, α-ketovalerate, and α-chloroisocaproate with I40 values mm), respectively, of 0.065, 0.49, 2.5, 0.2, 0.5, and 0.08. The concentration (mm) of α-ketoisocaproate, α-keto-β-methylvalerate, and α-ketoisovalerate needed to activate branched-chain α-ketoacid dehydrogenase in the perfused rat heart to 50% of total activity was 0.07, 0.10, and 0.25, respectively. Isolated branched-chain α-ketoacid dehydrogenase kinase was inhibited (I40 values, mm) by octanoate (0.5), acetoacetyl-CoA (0.01), methylmalonyl-CoA (0.2), NADP+ (1.5), and heparin (12 μg/ml). The kinase activity, in the presence or absence of ADP, was inhibited approximately 30% by 0.1 mm isobutyryl-CoA, isovaleryl-CoA, and malonyl-CoA, while not affected by NAD+ and NADH (1 mm), CoA, acetyl-CoA, methylcrotonyl-CoA, crotonyl-CoA, β-hydroxy-β-methyl-glutaryl-CoA, octanoyl-CoA, succinyl-CoA, and propionyl-CoA (0.1 mm). The following compounds at 2 mm also did not inhibit branched-chain α-ketoacid dehydrogenase kinase; acetate, propionate, β-hydroxybutyrate, lactate, acetoacetate, malonate, α-ketomalonate, succinate, citrate, oxaloacetate, FAD, and NADPH. These findings help explain the unique effects of Leu compared with Val and Ile on branched-chain amino acid metabolism and the differences between control of the kinases associated with pyruvate dehydrogenase and branched-chain α-ketoacid dehydrogenase.

Original languageEnglish
Pages (from-to)48-57
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume231
Issue number1
DOIs
StatePublished - May 15 1984

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3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Phosphotransferases
NADP
NAD
Malonyl Coenzyme A
Hydroxybutyrates
Oxaloacetic Acid
Branched Chain Amino Acids
Acetyl Coenzyme A
Flavin-Adenine Dinucleotide
Propionates
Succinic Acid
Coenzyme A
Pyruvic Acid
Metabolism
Citric Acid
Liver
Adenosine Diphosphate
Heparin
Rats

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Regulation of branched-chain α-ketoacid dehydrogenase kinase. / Paxton, Ralph; Harris, Robert.

In: Archives of Biochemistry and Biophysics, Vol. 231, No. 1, 15.05.1984, p. 48-57.

Research output: Contribution to journalArticle

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