L-carnitine as a detoxicant of nonmetabolizable acyl coenzyme A

Liver contains short-chain, medium-chain, and/or long-chain carnitine acyltransferases associated with mitochondria, peroxisomes, and microsomes. These data, plus the demonstration that elevated levels of acylcarnitines can occur in human urine due to impaired metabolism of specific acyl-CoAs, strongly support roles for L-carnitine in both modulating the acyl-CoA:CoA ratio and being an acceptor of specific nonmetabolizable acyl-CoAs. heretofore, an overlooked aspect of this metabolic problem has been the impact and implications of the inhibitory effects of acyl-CoAs, such as palmitoyl-CoA, on the short-chain carnitine acyltransferase activity. Herein, we show that palmitoyl-CoA is a potent inhibitor of carnitine acetyltransferase and that a secondary carnitine deficiency associated with a renal loss of carnitine can result in urinary excretion of specific alpha-keto acids that are substrates for the branched-chain alpha-keto acid dehydrogenase, pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase. These latter data indicate mitochondrial carnitine deficiency can result in inhibition of mitochondrial alpha-keto acid dehydrogenase activity.