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Journal of Lipid Research, Vol. 49, 1377-1387, July 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic Review Series: Glycerolipids. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids

Jean E. Vance¹

Group on the Molecular and Cell Biology of Lipids and Department of Medicine, University of Alberta, Edmonton, Alberta T6G 2S2, Canada

Published, JLR Papers in Press, January 19, 2008.

¹ To whom correspondence should be addressed. e-mail: jean.vance{at}ualberta.ca

Phosphatidylserine (PS) and phosphatidylethanolamine (PE) are two aminophospholipids whose metabolism is interrelated. 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 preexisting phospholipids are replaced by serine. PS synthase activity resides primarily on mitochondria-associated 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 knockout mice. Elimination of either pathway is embryonically lethal, despite the normal activity of the other pathway. PE can also be generated from a base-exchange reaction and by the acylation of lyso-PE. Cellular levels of PS and PE are tightly regulated by the implementation of multiple compensatory mechanisms.

Supplementary key words apoptosis • phosphatidylserine decarboxylation • phosphatidylserine synthase • CDP-ethanolamine pathway

Abbreviations: CHO, Chinese hamster ovary; ER, endoplasmic reticulum; MAM, mitochondria-associated membrane; PE phosphatidylethanolamine; PS, phosphatidylserine; PSD, phosphatidylserine decarboxylase

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