A molecular model of human branched-chain amino acid metabolism

Jul 17, 1998The American journal of clinical nutrition

A detailed model of how the body processes branched-chain amino acids

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Abstract

The activities of branched-chain amino acid (BCAA) catabolic enzymes were found to be higher in rat tissues compared to human and African green monkey tissues.

The overall enzyme activities of branched-chain-amino-acid aminotransferase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKD) are similar across the three species studied.
Skeletal muscle and liver account for over 70% of total oxidative capacity in humans, with muscle comprising a larger share compared to monkeys.
In humans, the brain may contribute 10-20% and the kidney 8-13% to whole-body BCAA metabolism.
A high ratio of transaminase to oxidative capacity in the gastrointestinal tract of primates may help retain essential BCAA carbon.
The expression of BCKD kinase (BCKDK) was detected in all human tissues, with the highest levels in muscle.

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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 alpha-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 alpha-keto acid pool. Quantitative polymerase chain reaction was used to examine expression of human branched-chain alpha-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.

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A molecular model of human branched-chain amino acid metabolism

Abstract

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