Inhibition of adenine nucleotide transport in rat liver mitochondria by long-chain acyl-coenzyme A beta-oxidation intermediates.
Long-chain acyl-coenzyme A esters (LCAC), which may accumulate under different pathological conditions and especially in patients with a mitochondrial fatty acid beta-oxidation defect, have long been known as potent inhibitors of several enzymes in multiple metabolic pathways, particularly the oxidative phosphorylation system (OXPHOS). To shed more light on the inhibitory mechanisms of acyl-CoA esters upon energy metabolism, the effect of palmitoyl-CoA and its beta-oxidation intermediates on OXPHOS was studied. We have recently shown that, using rat liver mitochondria, LCAC inhibit l-glutamate driven oxygen consumption in the presence of ADP whereas no effect is found when an uncoupler is used to stimulate respiration maximally. A similar inhibitory effect of these compounds is now reported upon the distribution of ATP for intra- and extra-mitochondrial utilization. Taken together these data strongly suggest that the inhibition of ADP-induced respiration with l-glutamate as substrate by LCAC is primarily due to inhibition of the mitochondrial ADP/ATP carrier.
Ventura
Fátima V
FV
Centro de Patogénese Molecular - Unidade de Biologia Molecular e Biopatologia Experimental, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal. fatima.ventura@ff.ul.pt
Tavares de Almeida
Isabel
I
Wanders
Ronald J A
RJ
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002956:Citrulline / Q000096:biosynthesis; D019298:Glucose-6-Phosphate / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D000214:Acyl Coenzyme A; D002956:Citrulline; D019298:Glucose-6-Phosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases