Acyltransferases and Transacylases Involved in Fatty Acid Remodeling of Phospholipids and Metabolism of Bioactive Lipids in Mammalian Cells

Abstract

Over 100 different phospholipid molecular species are known to be present in mammalian cells and tissues. Fatty acid remodeling systems for phospholipids including acyl-CoA: lysophospholipid acyltransferases, CoA-dependent and CoA-independent transacylation systems and lysophospholipase/transacylase are involved in the biosynthesis of these molecular species. Acyl-CoA:1-acyl-2-lysophospholipid acyltransferase prefers polyunsaturated fatty acyl-CoAs as acyl donors while acyl-CoA:2-acyl-1-lysophospholipid acyltransferase prefers saturated fatty acyl-CoAs. Therefore, the acyl-CoA:lysophospholipid acyltransferase system is involved in the synthesis of the phospholipid molecular species containing sn-1 saturated and sn-2 unsaturated fatty acids. The CoA-dependent transacylation system catalyzes the transfer of fatty acids esterified in phospholipids to lysophospholipids in the presence of CoA without the generation of free fatty acids. The CoA-dependent transacylation reaction in rat liver exhibits strict fatty acid specificity, i.e., three types of fatty acids (20:4, 18:2, and 18:0) are transferred. On the other hand, the CoA-independent transacylase catalyzes the transfer of C20 and C22 polyunsaturated fatty acids from diacyl phospholipids to various lysophospholipids, in particular, ether-containing lysophospholipids, in the absence of any cofactors. The CoA-independent transacylase is assumed to be involved in the accumulation of polyunsaturated fatty acids in ether-containing phospholipids and in the removal of deleterious ether-containing lysophospholipids. These acyltransferases and transacylases are involved in not only the remodeling of fatty acids but also the synthesis and degradation of some bioactive lipids and their precursors. In this review, the properties of these fatty acid remodeling systems and their possible roles in the biosynthesis of bioactive lipids are described.

Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes

“…The weak, but measurable lysoPE acyltransferase activity of mouse Aytl2, was detected in E. coli and reported in CHO-K1 microsomes (8). Enzymes with a similar specificity for lysoPC and lysoPE have also been reported in rat liver Golgi membranes (26) and other tissues (19).…”

“…Phospholipase-mediated deacylation, followed by reacylation of the lysophospholipid by using acyl-CoA, provides a pathway to remodel phospholipid molecular species in membranes. LPLAT activity, first described in the microsomal fraction of various tissues, has been characterized in many organisms (3,18,19).…”

Signaling Role for Lysophosphatidylcholine Acyltransferase 3 in Receptor-Regulated Arachidonic Acid Reacylation Reactions in Human Monocytes

“…It has traditionally been assumed that PL AA incorporation in activated cells may be secondary to the PLA 2 hydrolytic step because AA incorporates preferentially into the sn-2 position of PLs, and thus, for an enhanced AA reacylation to occur, 2-lysophospholipid acceptors, produced only by PLA 2 , should be provided. That lysophospholipid availability may limit AA reacylation in activated cells is also inferred from the finding that the specific activities of the enzymes of the reacylation pathway, ACSL and the CoA-dependent acyltransferases, are severalfold higher that that of PLA 2 in homogenates from resting and activated cells (23,(54)(55)(56)(57)(58).…”

Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity

“…Although various types of PLA 2 s have been identified and their biological functions were uncovered, the properties of LPLATs and their number have not been clarified. To date, numerous studies have suggested the possible presence of polyunsaturated long chain fatty acyl-CoA specific LPCATs, LPEATs, and LPSATs (5,(39)(40)(41)(42). Recently, we cloned and characterized two types of LPCAT: LPCAT1 and LysoPAFAT/LPCAT2.…”