Protective role of adenine nucleotide translocase in O2-deficient hearts.
At subsaturating concentrations of palmitoyl-CoA, the carnitine-dependent oxidation of the palmitoyl portion by uncoupled rat heart mitochondria was stimulated by ADP or ATP. This effect was traced to the prevention of acyl-CoA binding to adenine nucleotide translocase and the consequent sparing of acyl-CoA for acylcarnitine formation. Palmitoyl-CoA oxidation was stimulated by ITP also although ITP served neither as a transportable substrate nor as an inhibitor of ADP transport. ITP and other nontransportable nucleoside di(tri)phosphates prevented octanoyl-CoA binding to mitochondria. ITP was bound to mitochondria, and this binding was reversed by ADP, octanoyl-CoA, and carboxyatractyloside. Thus, besides a substrate site, there is a site on the translocase that binds nucleoside di(tri)phosphates, CoA and its esters, and atractylosides; inhibition of the translocase results, however, only from the binding of CoA esters of fatty acids and of atractylosides. We suggest that in O2-deficient hearts, when nucleotides decline and fatty acyl-CoA rises, the binding of the latter to the translocase becomes operational to slow fatty acylcarnitine production. By retarding the rise in amphipathic burden, this mechanism could protect heart against irreversible damage during brief periods of ischemia or hypoxia.
D000108:Acetylcarnitine / Q000096:biosynthesis; D000214:Acyl Coenzyme A / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D001665:Binding Sites; D005227:Fatty Acids / Q000378:metabolism; D007293:Inosine Triphosphate / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000502:physiology*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000502:physiology*; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D051381:Rats
D000214:Acyl Coenzyme A; D005227:Fatty Acids; C034681:octanoyl-coenzyme A; D007293:Inosine Triphosphate; D010171:Palmitoyl Coenzyme A; D001278:Atractyloside; D000244:Adenosine Diphosphate; D000108:Acetylcarnitine; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D009713:Nucleotidyltransferases; D010100:Oxygen; C003853:carboxyatractyloside