Branched-Chain Amino Acid Interactions in Skeletal Muscle: Isoleucine and L-Alloisoleucine

Abstract

Parenteral administration of a mixture of branched-chain amino acid (BCAA) solutions is known to alter plasma levels of the BCAA (ILE, LEU, VAL), their corresponding alpha-ketoacids (KMV, KIC, KIV) and L-alloisoleucine (ALLO), a stereoisomer of ILE. Although variously formulated mixtures of BCAA are administered, the metabolic implications of individual BCAA interactions have been only partially elucidated. Using the incubated, isolated, and intact rat epitrochlearis muscle, we measured the effect of graded increases (0.05, 0.10, 0.5, and 1.0 mM) in media concentrations of a single BCAA or ALLO on (1) the rate of decarboxylation of the other BCAA, and (2) the release of branched chain ketoacids from muscle. A graded increase of media ILE concentration to 1.0 mM changed the decarboxylation of LEU by —28%, and the release of KIC by +23%, but VAL decarboxylation increased by +25%, and the release of KIV declined by -56%. A graded increase of media LEU to 1.0 mM increased ILE decarboxylation by +146%, and its corresponding ketoacid (KMV) by +61%. Howevever, VAL decarboxylation changed by only +25% and KIV release declined by —65%. A graded increase in media VAL to 1.0 mM accelerated ILE decarboxylation by +37%, but KMV release was unchanged. Similarly, LEU decarboxylation fell by -26%, and the release of KIC by only +6%. ALLO 0.025 mM increased ILE release by +55% but had an inconsistent effect on ILE decarboxylation and did not alter protein synthesis or degradation (estimated by phenylalanine incorporation and tyrosine release, respectively). Increasing ILE did not affect ALLO release. This study provides further evidence for the unique role of individual BCAA and ALLO interactions at one of the major control points of BCAA degradation in skeletal muscle. Because the use of mixtures of BCAA as a therapeutic modality can result in specific alterations of individual plasma BCAA, the effects of variously formulated BCAA mixtures must be studied in detail before the full implications of their metabolic interactions are known. (Journal of Parenteral and Enteral Nutrition 10:456-462, 1986)