Regulation of branched-chain α-keto acid dehydrogenase kinase expression in rat liver

Robert A. Harris, Rumi Kobayashi, Taro Murakami, Yoshiharu Shimomura

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Branched-chain amino acids are toxic in excess but have to be conserved for protein synthesis. This is accomplished in large part by control of the activity of the branched-chain α-keto acid dehydrogenase complex by phosphorylation/dephosphorylation. Regulation of the activity of the hepatic enzyme appears particularly important, at least in rats, since an exceptional high activity of the complex in this tissue makes the liver the primary clearing house for excess branched-chain α-keto acids released by other tissues. The degree to which the branched-chain α-keto acid dehydrogenase complex is inactivated by phosphorylation is determined by the activity of the branched-chain α-keto acid dehydrogenase kinase, which is itself regulated by allosteric effectors as well as factors that affect its level of expression. Well established among these are the α-keto acid produced by leucine transamination, which is a potent inhibitor of the kinase, and starvation for dietary protein, which causes increased expression of the branched-chain α-keto acid dehydrogenase kinase. The latter finding resulted in the working hypothesis that nutrients and hormones regulate expression of the branched-chain α-keto acid dehydrogenase kinase. Evidence has been obtained for the involvement of thyroid hormone, glucocorticoids and ligands for peroxisome proliferator-activated receptor α. Thyroid hormone induces, whereas glucocorticoids and peroxisome proliferator-activated receptor α ligands repress, expression of the kinase. Increased blood levels of thyroid hormone are proposed to be responsible for increased expression of branched-chain α-keto acid dehydrogenase kinase in animals starved for protein.

Original languageEnglish (US)
Pages (from-to)841S-845S
JournalJournal of Nutrition
Volume131
Issue number3
DOIs
StatePublished - 2001

Keywords

  • Branched-chain amino acids
  • Dehydrogenase
  • Kinase
  • Leucine
  • Liver
  • Rat

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

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