Phosphatidylinositols inositol phosphoglycerides

As in a musical composition, there is a major chord, and on most occasions there is a minor chord. The same can be applied to phosphatidylinositol and its phosphorylated derivatives. Immediately above, there was mention of three major inositol-containing phosphoglycerides. Over the past few years, identification of so-called minor inositol phosphoglycerides has received in-... 

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... 

When attention is directed toward the phospholipase.C found in mammalian tissue, a rather unique and different substrate profile is evident. It appears that the most favored substrate status must be assigned to the inositol- containing phosphoglycerides, namely, phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2). There is some evidence that the plasma membrane of certain mammalian cells contains a phospholipase C with high specificity for the bisphosphate, PIP2. The latter enzymatic interaction would be closely associated with the signal transduction pathway in mammalian cells. 

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). 

Synthesis of phosphatidylinositol follows a slightly different pathway from the other phosphoglycerides. Phosphatidate is activated by CTP-phos-phatidate cytidyl transferase to form CDP-diacylglycerol. Free inositol is then incorporated by CDP-diacylglycerol inositol transferase, with the release of CMP. Phosphatidylinositol usually constitutes less than 5% of total milk phospholipids (Bitman and Wood, 1990). 

Phosphatidate is formed by successive acylations of glycerol 3-phosphate by acyl Co A. Flydrolysis of its phosphoryl group followed by acylation yields a triacylglycerol. CDP-diacylglycerol, the activated intermediate in the de novo synthesis of several phospholipids, is formed from phosphatidate and CTP. The activated phosphatidyl unit is then transferred to the hydroxyl group of a polar alcohol, such as inositol, to form a phospholipid such as phosphatidylinositol. In mammals, phosphatidylethanolamine is formed by CDP-ethanolamine and diacylglycerol. Phosphatidylethanolamine is methylated by S-adenosylmethionine to form phosphatidylcholine. In mammals, this phosphoglyceride can also be synthesized by a pathway that utilizes dietary choline. CDP-choline is the activated intermediate in this route. 

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