Evidence for a short-chain carnitine-acylcarnitine translocase in mitochondria specifically related to the metabolism of branched-chain amino acids

Carnitine-acylcarnitine translocase (CATR) deficiency is a severe defect in fatty acid oxidation which presents early in life most frequently with hyp oglycemia, hyperammonemia, and severe cardiac abnormalities. CATR exchanges acylcarnitines of various chain lengths for free carnitine across the mito chondrial membrane. lit vitro studies in intact fibroblasts from patients w ith documented deficiency of CATR were probed with stable-isotope-labeled p recursors and the resulting acylcarnitines were analyzed by tandem mass spe ctrometry, After a 72-h incubation with L-[H-2(3)]carnitine the translocase -deficient cells produced acylcarnitines in which the deuterium was incorpo rated into short-chain acylcarnitines, C2-C5. Experiments with simultaneous incubation of L-[H-2(3)]carnitine and L-[C-13(6)]isoleucine produced [C-13 (5)]2-methylbutyryl-[H-2(3)]carnitine and [C-13(3)]propionyl-[H-2(3)]carnit ine indicating exchange of labeled acylcarnitine from inside the mitochondr ial matrix with labeled free carnitine. These studies support the possible existence of a "branched-chain" carnitine-acylcarnitine translocator in mit ochondria, (C) 2000 academic Press.