Regulation of acetoacetyl-CoA in isolated perfused rat hearts.
The role of ketone bodies and long-chain fatty acids in regulating myocardial content of acetoacetyl-CoA was examined in isolated perfused hearts from fed rats. Addition of 10 mM acetoacetate to a perfusion medium containing 5.5 mM glucose as exogenous substrate resulted in a sevenfold increase of cardiac acetoacetyl-CoA content. Inclusion of 0.75--0.94 mM palmitate in the perfusate did not augment the basal level of acetoacetyl-CoA nor did it influence the already elevated content of the metabolic intermediate shown to exist in the presence of acetoacetate alone. In addition to the observed increase in myocardial acetoacetyl-CoA, a decrease in free carnitine in hearts perfused with acetoacetate was accompanied by elevated ratios of both acetylcarnitine/carnitine and long-chain fatty acylcarnitine/carnitine. Addition of palmitate in the presence of acetoacetate resulted in a further diminution of myocardial free carnitine leading to a further elevation of the long-chain fatty acylcarnitine/carnitine ratio when compared to hearts perfused with the ketone body alone. The changes in myocardial CoA and carnitine and their intermediates in hearts perfused with acetoacetate either alone or in combination with palmitate indicate that ketone bodies can divert fatty acids away from oxidation and toward esterification as triacylglycerols. Even though the interrelationships between ketones and myocardial fatty acid metabolism have not been fully characterized, a role for ketone bodies in promoting the increase in myocardial acetoacetyl-CoA found in diabetic ketoacidosis has been clearly defined.
D000090:Acetoacetates; D000105:Acetyl Coenzyme A / Q000031:analogs & derivatives* / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D066298:In Vitro Techniques; D007651:Keto Acids / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000090:Acetoacetates; D000214:Acyl Coenzyme A; D007651:Keto Acids; D007657:Ketone Bodies; D010169:Palmitic Acids; C010667:acetoacetyl CoA; D019308:Palmitic Acid; C016635:acetoacetic acid; D000105:Acetyl Coenzyme A