Carnitine Regulation of Fatty Acid Metabolism in Heart
Recent investigations of the distribution and functions of carnitine (β-hydroxy-γ-trimethyl ammonium butyrate) and its derivatives, have led to the general concept that carnitine may be involved in acyl group transfer from extra- to intramitochondrial compartments (l). According to this view, fatty acids are activated to CoA derivatives and transferred to mitochondria. At the outer mitochondrial membrane, carnitine acyl transferase (acyl CoA:carnitine O-acyl transferase) catalyzes transfer of the acyl group from CoA to carnitine, thereby facilitating membrane transport of the long-chain fatty acid. The acyl group is subsequently reconverted to the CoA derivative at the intramitochondrial site of fatty acid oxidation. Consonant with this hypothesis are the following evidences: a) carnitine favors the formation of acyl-carnltine, which in turn is a requisite for increased oxidation of the acyl group by isolated mitochondria (2); b) the rate of transfer of acyl groups across the mitochondrial membrane is presumably the main determinant of the rate of fatty acid oxidation (3); c) palmityl carnitine competitively inhibits carnitine stimulation of fatty acid oxidation in heart mitochondria (4).
KeywordsFatty Acid Oxidation Fatty Acid Synthesis Heart Mitochondrion Perfuse Heart Acetyl Carnitine
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