Energy-linked regulation of mitochondrial fatty acid oxidation in the isolated perfused rat heart.
Regulation of beta-oxidation under various metabolic conditions and energy loads was studied by employing a newly developed method for assaying 3-hydroxyacyl-CoA and 2-trans-enoyl-CoA intermediates of fatty acid oxidation. A 66% inhibition of oleate oxidation with a concomitant 68% inhibition of oxygen consumption resulted in a 81% decrease in the carnitine/acyl-carnitine ratio, but the concentrations of 2-trans-enoyl-CoA and 3-hydroxyacyl-CoA esters did not change significantly and the acid-insoluble acyl-CoA content did not change. The acetyl-CoA concentration increased three-fold, however, and there was a simultaneous tendency for the NADH/NAD+ ratio to shift towards oxidation. The results suggest that the main regulatory site of fatty acid oxidation resides at an early step in the pathway. Since the concentrations of the acyl-CoA derivatives identified did not undergo major changes even though the acyl-carnitine concentration changed some rate limitation must already occur at the steps of acyl transport into the mitochondria or the carnitine acyltransferase II.
Department of Medical Biochemistry, University of Oulu, Finland.
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Latipää
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002331:Carnitine / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D009829:Oleic Acids; D019301:Oleic Acid; D002331:Carnitine; D003065:Coenzyme A