PERIPHERAL METABOLISM OF BRANCHED-CHAIN KETO ACIDS IN PATIENTS WITH CHRONIC-RENAL-FAILURE

Peripheral tissue metabolism of branched-chain amino acids (BCAA) and branched-chain keto acids (BCKA) in the postabsorptive state was evalu ated in 8 patients with chronic renal failure (CRF) and 7 controls by measuring the arterial-deep forearm venous differences for BCAA and BC KA. Arterial whole blood levels of BCAA and BCKA were also measured in an additional 7 patients and 11 controls. In CRF, total BCKA levels a re reduced owing to a decrease in ketoisocaproic acid (KICA) and ketoi sovaleric acid (KIVA) levels, parallel to changes in BCAA levels, wher eas levels of ketomethylvaleric acid (KMVA) are not different from con trols. Both in normal conditions and in patients, arterial levels of i ndividual BCAA are directly correlated with arterial levels of the cor responding BCKA. However, in CRF, the ratios of leucine to KICA and of isoleucine to KMVA are increased. A direct correlation between KICA a nd HCO3- levels is observed. In CRF, the release of leucine and valine as well as of KICA and KMVA from peripheral tissues is reduced, where as KIVA is neither released nor taken up by the forearm. The lack of K ICA release from peripheral tissues likely accounts for its low circul ating levels. The depressed peripheral release of leucine associated w ith the lack of KICA release suggests an increased degradation of leuc ine which proceeds beyond the transamination step.