Microsomal fatty acyl-CoA transacylation and hydrolysis: fatty acyl-CoA species dependent modulation by liver fatty acyl-CoA binding proteins

Liver and intestinal cytosol contain abundant levels of long chain fatty ac yl-CoA binding proteins such as liver fatty acid binding protein (L-FABP) a nd acyl-CoA binding protein (ACBP). However, the relative function and spec ificity of these proteins in microsomal utilization of long chain fatty acy l-CoAs (LCFA-CoAs) for sequential transacylation of glycerol-3-phosphate to form phosphatidic acid is not known. The results showed for the first time that L-FABP and ACBP both stimulated microsomal incorporation of the monou nsaturated oleoyl-CoA and polyunsaturated arachidonoyl-CoA 8-10-fold and 2- 3-fold, respectively. In contrast, these proteins inhibited microsomal util ization of the saturated palmitoyl-CoA by 69% and 62%, respectively. These similar effects of L-FABP and ACBP on microsomal phosphatidic acid biosynth esis were mediated primarily through the activity of glycerol-3-phosphate a cyltransferase (GPAT), the rate limiting step, rather than by protecting th e long chain acyl-CoAs from microsomal hydrolase activity. In fact, ACBP bu t not L-FABP protected long chain fatty acyl-CoAs from microsomal acyl-CoA hydrolase activity in the order: palmitoyl-CoA > oleoyl-CoA > arachidonoyl- CoA. In summary, the data established for the first time a role for both L- FABP and ACBP in microsomal phosphatidic acid biosynthesis. By preferential ly stimulating microsomal transacylation of unsaturated long chain fatty ac yl-CoAs while concomitantly exerting their differential protection from mic rosomal acyl-CoA hydrolase, L-FABP and ACBP can uniquely function in modula ting the pattern of fatty acids esterified to phosphatidic acid, the de nov o precursor of phospholipids and triacylglycerols. This may explain in part the simultaneous presence of these proteins in cell types involved in fatt y acid absorption and lipoprotein secretion. (C) 2000 Elsevier Science B.V. All rights reserved.