Phosphatidylserine (PS) and phosphatidylethanolamine (PE) are two aminophospholipids whose metabolism is inter-related. Both phospholipids are components of mammalian cell membranes and play important roles in biological processes such as apoptosis and cell signaling. PS is synthesized in mammalian cells by base-exchange reactions in which polar head-groups of pre-existing phospholipids are replaced by serine. PS synthase activity resides primarily on mitochondriaassociated membranes and is encoded by two distinct genes. Studies in mice in which each gene has been individually disrupted are beginning to elucidate the importance of these two synthases for biological functions in intact animals. PE is made in mammalian cells by two completely independent major pathways. In one pathway, PS is converted into PE by the mitochondrial enzyme PS decarboxylase. In addition, PE is made via the CDP-ethanolamine pathway in which the final reaction occurs on the endoplasmic reticulum and nuclear envelope. The relative importance of these two pathways of PE synthesis has been investigated in knock-out mice. Elimination of either pathway is embryonically lethal despite normal activity of the other pathway. PE can also be generated from a base-exchange reaction and by the acylation of PE. Cellular levels of PS and PE are tightly regulated by implementation of multiple compensatory mechanisms. by guest, on September 9, 2017 www. jlr. org