Regulation of Metabolite Transport in Rat and Guinea Pig Liver Mitochondria by Long Chain Fatty Acyl Coenzyme A Esters

Abstract

Abstract Long chain fatty acyl coenzyme A esters were found to be potent inhibitors of adenine nucleotide translocation in both rat and guinea pig liver mitochondria. There was a positive correlation of inhibition with the carbon chain length and carnitine-dependent oxidation of the fatty acyl-CoA esters. Octanoyl-CoA was completely ineffective at concentrations up to 50 µm. Esters containing a greater number of carbon atoms produced significant inhibition at concentrations as low as 5 µm. Both saturated and unsaturated acyl-CoA esters were effective inhibitors, although there was some difference in effectiveness depending upon the concentration. Palmitoyl-CoA was shown to inhibit binding competitively with ADP in both nucleotide depleted mitochondria and Lubrol membrane fragments. The mode of inhibition and sensitivity of adenine nucleotide translocase to the acyl-CoA esters appeared to be similar to that produced by atractylate. Under conditions studied, the concentration of carnitine acyltransferase enzyme(s) did not influence the inhibition produced by the acyl-CoA esters. Phosphoenolpyruvate, known to be transported on the tricarboxylate carrier, also was found to be transported by the adenine nucleotide translocase in both rat and guinea pig liver mitochondria. In addition the tricarboxylate as well as adenine nucleotide translocator was inhibited by atractylate as well as long chain fatty acyl-CoA esters. These results suggest an important function of long chain fatty acyl-CoA esters in the regulation of mitochondrial metabolite transport.