MAMMALIAN MITOCHONDRIAL GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE

Glycerol-3-phosphate acyltransferase (GPAT) is the first committed, an d presumed to be a rate-limiting, step in glycerophospholipid biosynth esis. There are two isoforms of GPAT, a mitochondrial and a microsomal form. Mitochondrial GPAT has recently been purified and its gene has been cloned and expressed in baculovirus-infected cells. The GPAT acti vity was reconstituted using the purified enzyme and various phospholi pids. Mitochondrial GPAT prefers saturated fatty acyl-CoA as a substra te. This preference may contribute to the observed asymmetric distribu tion of saturated and unsaturated fatty acids at the sn-1 and sn-2 pos itions of cellular glycerophospholipids. A region of homology to vario us acyltransferases that may be important for catalysis or fatty acyl- CoA binding is present in mitochondrial GPAT. Mitochondrial GPAT is up regulated at the transcriptional level by refeeding a high carbohydrat e, fat-free diet to previously fasted mice and by insulin administrati on to diabetic animals, whereas microsomal GPAT activity is largely un affected by these treatments. (C) 1997 Elsevier Science B.V.