Interaction of acyl-CoA binding protein (ACBP) on processes for which acyl-CoA is a substrate, product or inhibitor.
It is shown that acyl-CoA binding protein (ACBP), in contrast with fatty 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 sequestration of the synthesized acyl-CoA esters. Feedback inhibition of microsomal 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. ACBP was found to have a strong attenuating effect on the long-chain acyl-CoA inhibition of both acetyl-CoA carboxylase and mitochondrial adenine nucleotide translocase. Both processes were unaffected by the presence of long-chain acyl-CoA esters when the ratio of long-chain acyl-CoA to ACBP was below 1, independent of the acyl-CoA concentration used. It is therefore not the acyl-CoA concentration as such which is important from a regulatory point of view, but the ratio of acyl-CoA to ACBP. 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 triacylglycerol-synthesizing pathway, but not with the phospholipid-synthesizing enzymes, for acyl-CoA esters. Furthermore, in contrast with FABP, ACBP was able to protect long-chain acyl-CoA esters against hydrolysis by microsomal acyl-CoA hydrolases. The results suggest that long-chain acyl-CoA esters synthesized for either triacylglycerol synthesis or beta-oxidation have to pass through the acyl-CoA/ACBP pool before utilization. This means that acyl-CoA synthesized by microsomal or mitochondrial synthetases is uniformly available in the cell. It is suggested that ACBP has a duel function in (1) creating a cytosolic pool of acyl-CoA protected against acyl-CoA hydrolases, and (2) protecting vital cellular processes from being affected by long-chain acyl-CoA esters.
Rasmussen
J T
JT
Institute of Biochemistry, Odense University, Denmark.
Rosendal
J
J
Knudsen
J
J
D000214:Acyl Coenzyme A / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007425:Intracellular Membranes / Q000378:metabolism*; D007700:Kinetics; D007774:Lactation; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism
D000214:Acyl Coenzyme A; D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins