A molecular model of human branched-chain amino acid metabolism

Agus Sitryawan, John W. Hawes, Robert A. Harris, Yoshiharu Shimomura, Anne E. Jenkins, Susan M. Hutson

Research output: Contribution to journalArticle

240 Scopus citations

Abstract

To establish an accurate molecular model of human branched-chain amino acid (BCAA) metabolism, the distribution, activity, and expression of the first 2 enzymes in the catabolic pathway-branched-chain-amino-acid aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKD) complex-were determined in human tissues. The same enzyme activities were measured in rat and African green monkey tissues. Overall, the activities of BCAT and BCKD were higher in rat than in human and monkey tissues; nevertheless, the ratio of the 2 activities was similar in most tissues in the 3 species. Total oxidative capacity was concentrated in skeletal muscle and liver (> 70%) with muscle having a higher proportion of the total in humans and monkeys. In humans, brain (10-20%) and kidney (8-13%) may contribute significantly to whole-body BCAA metabolism. Furthermore, in primates the high ratio of transaminase to oxidative capacity in the entire gastrointestinal tract serves to prevent loss of essential BCAA carbon and raises the possibility that the gastrointestinal tract contributes to the plasma branched-chain α-keto acid pool. Quantitative polymerase chain reaction was used to examine expression of human branched-chain α-keto acid dehydrogenase kinase (BCKDK), the key enzyme that regulates the activity state of the human BCKD complex and human BCAT isoenzymes. To design the primers for the polymerase chain reaction, human BCKDK was cloned. BCKDK message was found in all human tissues tested, with the highest amount in human muscle. As in rats, there was ubiquitous expression of mitochondrial BCAT, whereas mRNA for the cytosolic enzyme was at or below the limit of detection outside the brain. Finally, the role of BCAA in body nitrogen metabolism is discussed.

Original languageEnglish (US)
Pages (from-to)72-81
Number of pages10
JournalAmerican Journal of Clinical Nutrition
Volume68
Issue number1
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • African green monkeys
  • Branched-chain amino acid
  • Branched-chain α- keto acid dehydrogenase kinase
  • Branched-chain α-keto acid dehydrogenase
  • Branched-chainamino-acid aminotransferase
  • Essential amino acids
  • Human models
  • Metabolism
  • Rats

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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  • Cite this

    Sitryawan, A., Hawes, J. W., Harris, R. A., Shimomura, Y., Jenkins, A. E., & Hutson, S. M. (1998). A molecular model of human branched-chain amino acid metabolism. American Journal of Clinical Nutrition, 68(1), 72-81. https://doi.org/10.1093/ajcn/68.1.72