The biosynthesis of phosphatidylcholine and phosphatidyl ethanolamine also involves the conversion of phosphatidate to 1,2-diacylglycerol (see Figure 1). Before the next step, however, choline or ethanolamine must first be activated by phosphorylation by ATP and then linked to CDP. The resulting CDP-choline or CDP-ethanolamine reacts with 1,2-diacylglycerol to form either phosphatidylcholine or phosphatidylethanolamine, respectively (see Figure 1, lower left). In the case of phosphatidylinositol formation, it is phosphatidate that is linked to CDP, forming CDP-diacylglycerol, which is then linked to inositol by phosphatidylinositol synthase. The second messenger, phosphatidylinositol 4,5 bisphosphate (PIP2), which regulates essential cell functions including signal trans duction and vesicle trafficking, is synthesized by two further kinase catalyzed steps (see Figure 1, lower right). Phosphatidylserine is formed from phosphatidylethanolamine directly by reaction with serine. Phosphatidylserine may reform phosphatidylethanolamine by decarboxylation (see Figure 1, bottom left). An alternative pathway in liver enables phosphatidylethanolamine to give rise directly to phosphatidylcholine by progressive methylation of the ethanolamine residue. Despite these endogenous sources of choline, it is considered to be an essential nutrient for humans and many other mammalian species.
The regulation of triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine biosynthesis is driven by the availability of free fatty acids. Those not required for oxidation are preferentially converted to phospholipids, and when this requirement is satisfied, they are used for triacylglycerol synthesis.
Cardiolipin (diphosphatidylglycerol) is a phospholipid present in mitochondria. It is formed from phosphatidylglycerol, which in turn is synthesized from CDP diacylglycerol (see Figure 1) and glycerol-3-phosphate. Cardiolipin, found in the inner membrane of mitochondria, has a key role in mitochondrial structure and function, and is also thought to be involved in programmed cell death (apoptosis).
Fig1. Biosynthesis of triacylglycerol and phospholipids. 1, monoacylglycerol pathway; 2, glycerol phosphate pathway. Phosphatidylethanolamine may be formed from ethanolamine by a pathway similar to that shown for the formation of phosphatidylcholine from choline.
