cDNA Cloning, Expression and Chromosomal Localization of Two Human Lysophosphatidic Acid Acyltransferases

Abstract

Lysophosphatidic acid (l-acyl-sn-glycero-3-phosphate, LPA) is both a biochemical intermediate in phospholipid metabolism and a potent bioactive lipid with diverse activities that range from the physiologic to the pathophysiologic. As an intermediate, LPA can be formed by acylation of sn-glycerol-3-phosphate or by acylation of dihydroxyacetone phosphate (DHAP) followed by reduction of the acyl-DHAP¹. The LPA can be acylated further by the action of LPA acyltransferase (LPAAT) to form phosphatidic acid (PA), which preceeds diacylglycerol and CDP-diacylglycerol formation. LPA has also gained notoriety as a bioactive mediator that modulates mitogenesis, cell differentiation, platelet aggregation, actin cytoskeleton remodeling, monocyte chemotaxis, smooth muscle contraction, and neurite retraction². In vitro experiments suggest that LPA can also impact immune cell functions such as proliferation and IL-2 production³. The phospholipid may also participate in the pathophysiology of neurodegenerative processes by causing vasoconstriction as well as impairment of glutamate and glucose uptake by astrocytes^4,5. In addition, LPA is a potent promoter of tumor cell growth and invasion^6,7.