Carnitine acyltransferases in normal human skeletal muscle and in muscle of patients with carnitine palmitoyltransferase deficiency.

Carnitine acyltransferase activities were studied in normal human skeletal muscle and in muscle of three patients with carnitine palmitoyltransferase deficiency. Carnitine acetyltransferase (CAT), carnitine octanoyltransferase (COT), and carnitine palmitoyltransferase (CPT) were differentiated (i) by the use of the substrates acetyl-CoA, octanoyl-CoA, lauroyl-CoA, and palmitoyl-CoA, (ii) by the inhibitors malonyl-CoA, chlorpromazine, and dithio-bis-nitrobenzoic acid (DTNB), and (iii) by the solubilities of the carnitine acyltransferase activities after centrifugation at 48,000 g for 30 min. The results are consistent with the notion of three different carnitine acyltransferases in human skeletal muscle: a membrane-bound malonyl-CoA-sensitive CPT, a soluble malonyl-CoA-insensitive CAT, and a malonyl-CoA-sensitive COT that is not attached to the mitochondrial membrane. The different solubilities of the carnitine acyltransferases allow a clear differentiation of CPT from CAT and COT in homogenates of previously frozen muscle biopsies whereas a separate determination of CAT and COT is only partially possible. In patients with CPT deficiency total CPT activity was within the normal range but was abnormally inhibited by malonyl-CoA and chlorpromazine. Activities of carnitine acyltransferases with the substrates acetyl-CoA and octanoyl-CoA were normal indicating that the biochemical defect in CPT deficiency is confined to CPT without compensatory changes of CAT and COT.