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.
|Kerner, J; Zaluzec, E; Gage, D et al. (1994) Characterization of the malonyl-CoA-sensitive carnitine palmitoyltransferase (CPTo) of a rat heart mitochondrial particle. Evidence that the catalytic unit is CPTi. J Biol Chem 269:8209-19|
|Chung, C D; Bieber, L L (1993) Properties of the medium chain/long chain carnitine acyltransferase purified from rat liver microsomes. J Biol Chem 268:4519-24|
|Huang, Z H; Gage, D A; Bieber, L L et al. (1992) Analysis of acylcarnitines as their N-demethylated ester derivatives by gas chromatography-chemical ionization mass spectrometry: clinical applications. Prog Clin Biol Res 375:363-8|
|Chung, C H; Woldegiorgis, G; Dai, G et al. (1992) Conferral of malonyl coenzyme A sensitivity to purified rat heart mitochondrial carnitine palmitoyltransferase. Biochemistry 31:9777-83|
|Murthy, M S; Bieber, L L (1992) Purification of the medium-chain/long-chain (COT/CPT) carnitine acyltransferase of rat liver microsomes. Protein Expr Purif 3:75-9|
|Lilly, K; Chung, C; Kerner, J et al. (1992) Effect of etomoxiryl-CoA on different carnitine acyltransferases. Biochem Pharmacol 43:353-61|
|Huang, Z H; Gage, D A; Bieber, L L et al. (1991) Analysis of acylcarnitines as their N-demethylated ester derivatives by gas chromatography-chemical ionization mass spectrometry. Anal Biochem 199:98-105|
|Chung, C; Chung, C D; Bieber, L L (1991) Purification of heart and liver mitochondrial carnitine acetyltransferase. Protein Expr Purif 2:426-31|
|Melegh, B; Kerner, J; Jaszai, V et al. (1990) Differential excretion of xenobiotic acyl-esters of carnitine due to administration of pivampicillin and valproate. Biochem Med Metab Biol 43:30-8|
|Lilly, K; Bugaisky, G E; Umeda, P K et al. (1990) The medium-chain carnitine acyltransferase activity associated with rat liver microsomes is malonyl-CoA sensitive. Arch Biochem Biophys 280:167-74|
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