Glycerophosphate/Acylglycerophosphate acyltransferases

Abstract

Acyl-CoA:glycerol-3-phosphate acyltransferase (GPAT) and acyl-CoA: 1-acyl-glycerol-3-phosphate acyltransferase (AGPAT) are involved in the de novo synthesis of triacylglycerol (TAG) and glycerophospholipids. Many enzymes belonging to the GPAT/AGPAT family have recently been identified and their physiological or pathophysiological roles have been proposed. The roles of GPAT/AGPAT in the synthesis of TAG and obesity-related diseases were revealed through the identification of causative genes of these diseases or analyses of genetically manipulated animals. Recent studies have suggested that some isoforms of GPAT/AGPAT family enzymes are involved in the fatty acid remodeling of phospholipids. The enzymology of GPAT/AGPAT and their physiological/ pathological roles in the metabolism of glycerolipids have been described and discussed in this review.

Figure 1

(a) Biosynthetic pathway of TAG and glycerophospholipids. GPAT (i) and AGPAT (ii) are involved in the common biosynthetic pathway of TAG and glycerophospholipids. After the de novo synthesis of phospholipids, individual phospholipids are subjected to fatty acid remodeling. Acyl-CoA:lysophospholipid acyltransferase (iii) reactions are involved in the fatty acid remodeling pathways of glycerophospholipids. The reactions of GPAT/AGPAT and acyl-CoA:lysophospholipid acyltransferase are shown in (b) and (c).

Figure 2

(a) Acyltransferase motifs in GPATs, AGPATs, tafazzin, and CGI-58. The conserved amino acid residues are shown in color; (b) Effects of amino acid substitutions at the human AGPAT1 acyltransferase motifs on AGPAT activity. The figure has been modified from Yamashita et al. [12].

Figure 3

(a) Predicted transmembrane segments and relationship to the acyltransferase motifs of GPAT/AGPAT family enzymes. The transmembrane segments of each enzyme were predicted by several algorithms including TMHMM and SOSUI. The locations of acyltransferase motifs I-IV have also been depicted; (b) Proposed models of the catalytic sites of AGPAT1 and GPAT1. The top or bottom sides of the membrane show the cytosol or lumen (interspace) of the ER and mitochondrial outer membranes.