A role for carnitine palmitoyltransferase, CPT, in mitochondrial beta- oxidation of long-chain fatty acids is well-established and the evidence for a role for mitochondrial carnitine acetyltransferase, CAT, in modulation of the short-chain acyl-CoA/CoASH ration is strong. Similarly, the evidence for a role for CAt, as well as carnitine octanoyltransferase, COT, in the peroxisomal chain-shortening of long- chain fatty acids is very strong [Ann. Rev, BCH 57, 261 (1988(]; however, the roles for CAT and COT of liver microsomes are unknown due, in part, to the limited studies with these two enzymes.
One specific aim of this proposal is to purify and characterize CAT and COT from rat liver microsomes. The enzymes will be rigorously characterized, including determination of partial amino acid sequences, and their properties will be compared to the other carnitine acyltransferases of liver. The other specific aim is to determine which of the liver carnitine acyltransferases have the enzymatic capacity to form unusual acylcarnitines that occur in some disease states and others that are produced due to the metabolism of selected drugs such as pivampicillin. Acyl-CoAs such as pivaloyl-, valproyl-, alpha-methuyloctanoyl-, and glutaryl-CoA will be prepared to use as substrates to determine which of the liver the respective acylcarnitines. It seems likely that microsomal COT and/or CAT participates in some of the above-mentioned conjugations. The long-term goal of this project is to elucidate the function(s) of short-chain and medium-chain carnitine acyltransferases in mammalian metabolism.
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