Phosphoglyceride biosynthesis

3 A novel cofactor for phospholipid synthesis was found by accident 

4 Further studies have revealed important features of the enzymes concerned in the CDP-base pathways 

PtdlnsP2 = Phosphatidylinositol 4,5-b/sphosphate PtdOH = Phosphatidic acid 

Both phosphatidylcholine and phosphatidylethanolamine can be made by pathways that are alternative to the CDP-base routes. Indeed, five methods for synthesizing phosphatidylcholine have been described (Table 7.1). In the second method, the primary amino group of phosphatidylethanolamine is methylated three times using 5-adenosylmethionine as a donor. 

In animal and plant tissues this pathway is of much less importance than the one using CDP-choline - in mammals only the liver uses this method to any extent (20-40% of the total phosphatidylcholine synthesized) - but it is the method used in those bacteria which contain phosphatidylcholine. The other three pathways generally have low activity but may be important in special circumstances. For example, the acylation of monoacylphos-phatidylcholine is used for the incorporation of specific fatty acids into phosphatidylcholine and may be the main method by which arachidonic acid is acylated at the sn-2 position (section 3.4.9). The transacylation (method 5) reaction takes place between two molecules of 1-monoacyl-phosphatidylcholine and, because saturated fatty acids are esterified at 

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Two routes to phospholipid biosynthesis are known in either, the participation of CTP is necessary. The first route involves phosphatidic acid in phosphoglyceride biosynthesis. Phosphatidic acid reacts with CTP to yield CDP-diglyceride which, as a coenzyme, can participate in the transfer of diglyceride onto serine (or inositol) to produce phosphatidylserine (or phosphatidylinositol). Serine phosphatides are liable to decarboxylation (pyridoxal phosphate acting... 

Key 3-carbon intermed. in alcoholic fermentation and glycolysis. Shows bacterial props., inhibitor of phosphoglyceride biosynthesis. 

Phosphatidic acids not only are intennediates in the biosynthesis of triacylglycerols but also are biosynthetic precursors of other members of a group of compounds called phosphoglycerides or glycerol phosphatides. Phosphorus-containing derivatives of lipids are known as phospholipids, and phosphoglycerides are one type of phospholipid. 

These compounds are well established as important intermediates in the biosynthesis of phosphoglycerides, such as phosphatidylcholine. The fact that they are formed on agonist stimulation of a cell suggested a role in the cell signaling process (Exton, 1990). In addition, over a period of many years, there have been reports on the interrelation of phosphatidic acid formation and cellular responses (Ca2+ movements to agonists, for example). Thus, these compounds have emerged as important components of cellular metabolism and merit serious attention in any metabolic investigation. 

Phosphoglycerides may be synthesized either from phosphatidic add or by the so-called salvage pathway. Phosphatidic acid is also an intermediate in triglyceride biosynthesis (Figure 19.4). The phosphatidic acid pathway is relatively minor in eukaryotes phosphatidic acid reacts with CTP to form CDP diglyceride (see Figure 19.15), and the latter may then react with choline or inositol to form phosphatidylinositol or phosphatidylcholine, as in Equations (19.14) and (19.15). 

Aveldano de Caldironi M. Bazan N. Composition and biosynthesis of meolcular species of retina phosphoglycerides. Neurochemistry 1980 1 381-392. 

Contrast the biosynthesis of phosphoglycerides in bacteria and mammals. Note the significance of CDP-diacylglycerol and CDP-choline or CDP-ethanolamine, the activated precursors in these biosyntheses. 

Lipotropic substances compounds directly or indirectly involved in fat metabolism, which can prevent or correct fatty degeneration of the liver. They serve as substrates of phosphatide biosynthesis, or contribute (e.g. by methylation) to the synthesis of these substrates. Thus choline and any substance capable of contributing methyl groups for choline synthesis (e.g. methionine) are L.s. Liver is the major site of synthesis of plasma phosphoglycerides when the availability of choline is restricted, the rate of phosphatidylcholine synthesis decreases, and the rate of removal of fatty acids from the liver falls below normal. If the rate of supply of fatty acids (free and esterified) to the liver remains normal, the resulting accumulation of fat gives rise to the condition of fatty liver, or fatty degeneration of the liver. 

Kennedy also demonstrated the central role of phosphatidic acid in both phospholipid (section 7.1.2) and triacylglycerol biosynthesis and one of his outstanding contributions has been to point out that the diacylglycerol derived from phosphatidic acid forms the basic building block for triacyl-glycerols as well as phosphoglycerides. 

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