Vance Jean E
Canadian Institutes for Health Research Group on Molecular and Cell Biology of Lipids, Department of Medicine, University of Alberta, 332 HMRC, Edmonton, AB, Canada T6G 2S2.
Prog Nucleic Acid Res Mol Biol. 2003;75:69-111. doi: 10.1016/s0079-6603(03)75003-x.
In this review, the pathways for phosphatidylserine (PS) and phosphatidylethanolamine (PE) biosynthesis, as well as the genes and proteins involved in these pathways, are described in mammalian cells, yeast, and prokaryotes. In mammalian cells, PS is synthesized by a base-exchange reaction in which phosphatidylcholine or PE is substrate for PS synthase-1 or PS synthase-2, respectively. Isolation of Chinese hamster ovary cell mutants led to the cloning of cDNAs and genes encoding these two PS synthases. In yeast and prokaryotes PS is produced by a biosynthetic pathway completely different from that in mammals: from a reaction between CDP-diacylglycerol and serine. The major route for PE synthesis in cultured cells is from the mitochondrial decarboxylation of PS. Alternatively, PE can be synthesized in the endoplasmic reticulum (ER) from the CDP-ethanolamine pathway. Genes and/or cDNAs encoding all the enzymes in these two pathways for PE synthesis have been isolated and characterized. In mammalian cells, PS is synthesized on the ER and/or mitochondria-associated membranes (MAM). PS synthase-1 and -2 are highly enriched in MAM compared to the bulk of ER. Since MAM are a region of the ER that appears to be in close juxtaposition to the mitochondrial outer membrane, it has been proposed that MAM act as a conduit for the transfer of newly synthesized PS into mitochondria. A similar pathway appears to operate in yeast. The use of yeast mutants has led to identification of genes involved in the interorganelle transport of PS and PE in yeast, but so far none of the corresponding genes in mammalian cells has been identified. PS and PE do not act solely as structural components of membranes. Several specific functions have been ascribed to these two aminophospholipids. For example, cell-surface exposure of PS during apoptosis is thought to be the signal by which apoptotic cells are recognized and phagocytosed. Translocation of PS from the inner to outer leaflet of the plasma membrane of platelets initiates the blood-clotting cascade, and PS is an important activator of several enzymes, including protein kinase C. Recently, exposure of PE on the cell surface was identified as a regulator of cytokinesis. In addition, in Escherichia coli, PE appears to be involved in the correct folding of membrane proteins; and in Drosophila, PE regulates lipid homeostasis via the sterol response element-binding protein.
在本综述中，描述了哺乳动物细胞、酵母和原核生物中磷脂酰丝氨酸（PS）和磷脂酰乙醇胺（PE）的生物合成途径，以及参与这些途径的基因和蛋白质。在哺乳动物细胞中，PS通过碱基交换反应合成，其中磷脂酰胆碱或PE分别作为PS合酶-1或PS合酶-2的底物。中国仓鼠卵巢细胞突变体的分离导致了编码这两种PS合酶的cDNA和基因的克隆。在酵母和原核生物中，PS通过与哺乳动物完全不同的生物合成途径产生：由CDP-二酰甘油与丝氨酸之间的反应产生。培养细胞中PE合成的主要途径是PS的线粒体脱羧作用。另外，PE可以在内质网（ER）中通过CDP-乙醇胺途径合成。已经分离并鉴定了编码这两种PE合成途径中所有酶的基因和/或cDNA。在哺乳动物细胞中，PS在内质网和/或线粒体相关膜（MAM）上合成。与内质网主体相比，PS合酶-1和-2在MAM中高度富集。由于MAM是内质网中似乎与线粒体外膜紧密并列的区域，因此有人提出MAM作为将新合成的PS转移到线粒体中的通道。类似的途径似乎在酵母中起作用。酵母突变体的使用导致了参与酵母中PS和PE细胞器间转运的基因的鉴定，但到目前为止，尚未鉴定出哺乳动物细胞中的相应基因。PS和PE并非仅作为膜的结构成分起作用。这两种氨基磷脂具有多种特定功能。例如，细胞凋亡过程中PS在细胞表面的暴露被认为是凋亡细胞被识别和吞噬的信号。血小板质膜从内膜小叶向外膜小叶的PS易位启动了血液凝固级联反应，并且PS是包括蛋白激酶C在内的几种酶的重要激活剂。最近，PE在细胞表面的暴露被确定为胞质分裂的调节剂。此外，在大肠杆菌中，PE似乎参与膜蛋白的正确折叠；在果蝇中，PE通过固醇反应元件结合蛋白调节脂质稳态。
