Phospholipid biosynthesis (WP9)

Phospholipids are amphipathic molecules that consist of a glycerol backbone esterified to a phosphate group and two fatty acids. As a primary structural element of biological membranes, phospholipids play important roles in cell morphology and organelle function. The major phospholipids found in total cell extracts from S. cerevisiae are phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS); however, the phospholipid composition of yeast changes according to the carbon source used for growth. All major phospholipid classes in S. cerevisiae may trace their synthesis to a common precursor: cytidine diphosphate diacylglycerol (CDP-DAG). CDP-DAG is synthesized in a reaction catalyzed by CDP-DAG synthase, which converts phosphatidic acid (PA) to CDP-DAG using cytidine triphosphate (CTP) as the CDP donor. There are two distinct CDP-DAG synthases in S. cerevisiae: Cds1p, localized in the endoplasmic reticulum (ER), and Tam41p, localized in the mitochondrial matrix. In the ER, CDP-DAG generated by Cds1p can be converted to phosphatidylinositol (PI) or phosphatidylserine (PS) via PI synthase (Pis1p) or PS synthase (Cho1p), respectively. In the mitochondrion, CDP-DAG generated by Tam41p can be sequentially converted to phosphatidylglycerol (PG), which can be further converted to cardiolipin. Synthesis of PI, PG, and cardiolipin occurs through similar mechanisms in mammalian cells; however, unlike yeast, mammals primarily synthesize PS from other phospholipids and not from CDP-DAG. Description adapted from YeastPathways https://pathway.yeastgenome.org/.

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