Competition between fatty acids and carbohydrate or ketone bodies as metabolic fuels for the isolated perfused heart.
The ability of carbohydrate fuels (lactate, pyruvate, glucose) and the ketone bodies (acetoacetate, beta-hydroxybutyrate) to compete with fatty acids as fuels of respiration in the isolated Langendorf-perfused heart was studied. Oleate and octanoate were used as fatty acid fuels since oleate requires carnitine for entry into mitochondria, whereas octanoate does not. The two ketone bodies inhibited the oxidation of both oleate and octanoate implying an intramitochondrial site of action. Pyruvate, lactate, and lactate plus glucose inhibited oleate oxidation but not octanoate oxidation, indicating a mechanism of inhibition that involves the carnitine system. Pyruvate was a more potent inhibitor than lactate at equal concentrations, but the effect of lactate could be greatly increased by dichloroacetate, an inhibitor of pyruvate dehydrogenase kinase. The physiological and mechanistic implications of these observations are discussed.
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000494:pharmacology; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D002241:Carbohydrates / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000494:pharmacology; D007657:Ketone Bodies / Q000494:pharmacology*; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D000090:Acetoacetates; D002210:Caprylates; D002241:Carbohydrates; D005227:Fatty Acids; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D007773:Lactates; D009829:Oleic Acids; D011773:Pyruvates; D002245:Carbon Dioxide; D019301:Oleic Acid; D019344:Lactic Acid; C016635:acetoacetic acid; D019289:Pyruvic Acid; D005947:Glucose; C031492:octanoic acid; D020155:3-Hydroxybutyric Acid