Abstract
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.
Highlights
BIOLOGICAL FUNCTIONS OF PHOSPHATIDYLSERINE AND PHOSPHATIDYLETHANOLAMINE INMAMMALIAN CELLS is primarily the result of the distinct fatty acyl chains esterified to the sn-1 and sn-2 positions of the glycerol backbone as well as the different polar head groups attached to the sn-3 position of the glycerol backbone
Phosphatidylserine(PS)andphosphatidylethanolamine (PE) are two aminophospholipids whose metabolism is interrelated
The rate-limiting reaction of the CDP-ethanolamine pathway for PE synthesis is catalyzed by another cytosolic enzyme, CTP:phosphoethanolamine cytidylyltransferase, which converts phosphoethanolamine into CDP-ethanolamine (Fig. 1) [126,127,128,129]
Summary
MAMMALIAN CELLS is primarily the result of the distinct fatty acyl chains esterified to the sn-1 and sn-2 positions of the glycerol backbone as well as the different polar head groups attached to the sn-3 position of the glycerol backbone. In the plasma membrane, PS and PE are asymmetrically distributed across the bilayer such that the great majority (.80%) of these aminophospholipids are normally confined to the inner leaflet, whereas phosphatidylcholine and sphingomyelin are enriched on the outer leaflet. The asymmetric transbilayer distribution of PS in the plasma membrane of mammalian cells is thought to be established and maintained by a continuous unidirectional transbilayer movement of PS from the external surface to the cytosolic surface of the plasma membrane. This process requires ATP, but the aminophospholipid translocase that mediates the “flipping” of PS has not been unambiguously identified. PE is the donor of the ethanolamine moiety of the glycosylphosphatidylinositol anchors of many cell surface signaling proteins [47] and is a precursor of anandamide [N-arachidonoylethanolamine [48]], which is a ligand for cannabinoid receptors in the brain [49]
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