INTERACTION OF ACYL-COA-BINDING PROTEIN (ACBP) ON PROCESSES FOR WHICHACYL-COA IS A SUBSTRATE, PRODUCT OR INHIBITOR

It is shown that acyl-CoA binding protein (ACBP), in contrast with fat ty acid binding protein (FABP), stimulates the synthesis of long-chain acyl-CoA esters by mitochondria. ACBP effectively opposes the product feedback inhibition of the long-chain acyl-CoA synthetase by sequestr ation of the synthesized acyl-CoA esters. Feedback inhibition of micro somal long-chain acyl-CoA synthesis could not be observed, due to the formation of small acyl-CoA binding vesicles during preparation and/or incubation. Microsomal membrane preparations are therefore unsuitable for studying feedback inhibition of long-chain acyl-CoA synthesis. AC BP was found to have a strong attenuating effect on the long-chain acy l-CoA inhibition of both acetyl-CoA carboxylase and mitochondrial aden ine nucleotide translocase. Both processes were unaffected by the pres ence of long-chain acyl-CoA esters when the ratio of long-chain acyl-C oA to ACBP was below 1, independent of the acyl-CoA concentration used . It is therefore not the acyl-CoA concentration as such which is impo rtant from a regulatory point of view, but the ratio of acyl-CoA to AC BP. The cytosolic ratio of long-chain acyl-CoA to ACBP was shown to be well below 1 in the liver of fed rats. ACBP could compete with the tr iacylglycerol-synthesizing pathway, but not with the phospholipid-synt hesizing enzymes, for acyl-CoA esters. Furthermore, in contrast with F ABP, ACBP was able to protect long-chain acyl-CoA esters against hydro lysis by microsomal acyl-CoA hydrolases. The results suggest that long -chain acyl-CoA esters synthesized for either triacylglycerol synthesi s or beta-oxidation have to pass through the acyl-CoA/ACBP pool before utilization. This means that acyl-CoA synthesized by microsomal or mi tochondrial synthetases is uniformly available in the cell. It is sugg ested that ACBP has a duel function in (1) creating a cytosolic pool o f acyl-CoA protected against acyl-CoA hydrolases, and (2) protecting v ital cellular processes from being affected by long-chain acyl-CoA est ers.