On rate-controlling factors of long chain fatty acid oxidation.

Under appropriate conditions, mitochondria from red and white skeletal muscle of rabbit and from heart and liver of rat respired as rapidly with palmitoyl-coenzyme A plus carnitine as with palmitoyl carnitine. The ability of heart and skeletal muscle mitochondria to oxidize palmitoyl groups is limited by the acetyl-CoA-producing capacity of the 0 oxidation cycle rather than through a limitation of the citric acid cycle or by the capacity of electron transport oxidative phosphorylation system. In liver mitochondria, however, acetylCoA production from palmitoyl group appears to be limited by the capacity of the electron transport oxidative phosphorylation system. Mitochondria of liver, like those of heart or skeletal muscles, oxidize pahnitoyl groups nearly completely to CO2 when the citric acid cycle is functional but only to the oxidation level of acetate when the operation of the citric acid cycle is blocked. Under the latter conditions, the rate of acetyl group production from pahnitoyl group increases in mitochondria of liver but not in those of heart or of skeletal muscles. Thus ketone body production in liver may be dependent on the suppression of the citric acid cycle. The activities of carnitine pahnitoyltransferase and of ATP-dependent long chain acyl-CoA synthetase are unlikely to limit fatty acid oxidation in tissues of adult animals. It is suggested that the prevailing concentration ratio of long chain acyl-CoA esters to that of ADP near mitochondria may be one of the important factors that normally controls the rate of long chain fatty acid oxidation in ho.