Phosphatidic acid, a key intermediate in lipid metabolism

Phosphatidic acid (PtdOH) is a key intermediate in glycerolipid biosynthesi s. Two different pathways an known for de novo formation of this compound, namely (a) the Gro3P (glycerol 3-phosphate) pathway, and (b) the GrnP (dihy droxyacetone phosphate) pathway. Whereas the former route of PtdOH synthesi s is present in bacteria and all types of eukaryotes, the GrnP pathway is r estricted to yeast and mammalian cells. In this review article, we describe the enzymes catalyzing de novo formation of PtdOH, their properties and th eir occurrence in different cell types and organelles. Much attention has r ecently been paid to the subcellular localization of enzymes involved in th e biosynthesis of PtdOH. In all eukaryotic cells, microsomes (ER) harbour t he complete set of enzymes catalyzing these pathways and are thus the usual organelle for PtdOH formation. In contrast, the contribution of mitochondr ia to PtdOH synthesis is restricted to certain enzymes and depends on the c ell type. In addition, chloroplasts of plants, lipid particles of the yeast , and peroxisomes of mammalian cells are significantly involved in PtdOH bi osynthesis. Redundant systems of acyltransferases, the interplay of organel les, regulation of the pathway on the compartmental level, and finally the contribution of alternative pathways (phosphorylation of diacylglycerol and cleavage of phospholipids by phospholipases) to PtdOH biosynthesis appear to be required for the balanced formation of this important Lipid intermedi ate. Dysfunction of enzymes involved in PtdOH synthesis can result in sever e defects of various cellular processes. In this context, the possible phys iological role(s) of PtdOH and its related metabolites, lysophosphatidic ac id and diacylglycerol, will be discussed.