Acyl-GPC and alkenyl/alkyl-GPC:acyl-CoA acyltransferases

In mammalian tissues, phosphatidylcholine, or 1,2-diacyl-glycerophosphocholine (GPC), is the most abundant form of choline-containing phospholipids. In some electrically active tissues, a significant portion of the choline-containing phospholipids is 1-alkenyl-2-acyl-GPC (plasmenylcholine). The 1-alkyl-2-acyl-GPC is found in significant amounts in circulating cells such as neutrophils and macrophages but in low amounts in other tissues. Structural studies of phosphatidylcholine indicate that there is an asymmetric distribution of acyl groups on the molecule. Saturated fatty acids are usually esterified at the sn-1 position of the glycerol backbone, whereas unsaturated fatty acids are esterified at the sn-2 position. Similarly, unsaturated acyl groups are usually found in the sn-2 position of plasmenylcholine. The remodelling of the sn-2 acyl group in phosphatidylcholine by the deacylation-reacylation process has been demonstrated in a number of tissues. Phospholipase A2 is responsible for the hydrolysis of the acyl group at the sn-2 position, whereas 1-acyl-GPC:acyl-CoA acyltransferase is responsible for the reacylation reaction. The acyltransferase is located in the microsomal fraction and displays specificity towards the polyunsaturated acyl groups. The enzyme can be solubilized by detergent, but the enzyme activity in soluble form is difficult to maintain. The acyltransferase for the reacylation of 1-alkenyl-GPC is also located in the microsomal fraction and is somewhat specific towards polyunsaturated acyl groups. In guinea pig heart mitochondria, however, a new form of 1-alkenyl-GPC acyltransferase was identified which appeared to be different from the microsomal form. The acyltransferase for the acylation of 1-alkyl-GPC into platelet-activating factor has been studied in several tissues including human neutrophils. At present, the contribution of the acyltransferase in attaining the observed molecular composition of the choline-containing phospholipids in the tissue has not been defined. We postulate that the intrinsic acyl-CoA specificity of the acyltransferase, the flux of 1-acyl-GPC, 1-alkenyl-GPC and 1-alkyl-GPC, as well as the pool size of acyl-CoA are major factors in producing the final composition of the molecular species of the choline-containing phospholipids.