Biosynthesis of Glycerophosphatides

When a suitably labelled precursor is administered to an animal, the label appears in the glycerophosphatides of most tissues. This is true for a wide variety of precursors, including orthophosphate labelled with fatty acid labelled with H, or elaidic acid acetate labelled with or glycerol labelled with 

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Figure 2. Biosynthesis of glycerophosphatides. Figures in parentheses refer to equations in text.

Glycerophosphatides. These lipids are mainly acyl derivatives of a-glycerophosphoric acid and often are called phospholipids. The simplest glycerophosphatides are the phosphatidic acids, which contain a-glycerophosphoric acid esterified with two fatty acids (Fig. III-37). Small quantities of phosphatidic acids have been isolated from a wide variety of plant and animal tissues. It is doubtful that these compounds exist in large amounts in tissues, because more complex glycerophosphatides are readily hydrolyzed by enzymes that are widely distributed in such tissues, yielding phosphatidic acids. Phosphatidic acid is a crucial intermediate in the biosynthesis of phospholipids. 

The 1, 2-diglyceride arises by a dephosphorylation of a diacyl-phospha-tidic acid (a glycerophosphatide without the base) in the presence of a specific phosphatase. The phosphatidic acids which are intermediates in the biosynthesis of lecithins are the result of a combination, in the presence of ATP and a specific enzyme, of a-glycerophosphoric acid with two molecules of fatty add activated by CoA. These compounds of aliphatic acids and CoA are provided by the fatty acid cycle functioning in the direction of biosynthesis. The enzyme catalysing acyl transfer has a special spedfidty for the acyl-CoA derivatives of the Cu and Cjg acids. 

The parent compound of the glycerophosphatides is L-a-phosphatidic acid (I), a substance now known to be an important intermediate in the biosynthesis of most of these lipids. 

In the biosynthesis of many of the glycerophosphatides, phosphatidic acid is first dephosphorylated. Smith, Weiss and Kennedy (1957) showed that liver contains an enzyme, phosphatidic acid phosphatase (L-a-phosphatidate phospho-hydrolase EC 3.1.3.4), which removes phosphate from phosphatidic acid with the formation of D-a, j8-diglyceride (II) ... 

A major advance in the understanding of the biosynthesis of the glycerophos-phatides was the discovery by Kennedy and Weiss (1956) of the role of nucleotides of cytosine in the biosynthesis of the glycerophosphatides. Cytidine 5 -triphosphate (CTP) was shown to be necessary for the incorporation of phosphorylcholine into lecithin by liver preparations. Similar observations have been reported for brain (McMubbay et al. 1957, Stbickland et al. 1963) and other tissues. The nucleotide requirement is specific for CTP, none of the other nucleoside 5 -triphosphates being active. Kennedy and Weiss (1956) showed that CTP combines with phosphorylcholine to form the intermediate CDP-choline (IV) according to the equation ... 

This discussion will be confined to a general description of the biosynthesis and degradation of the glycerophosphatides commonly found in animal tissues. Reference will be made to the glycerophosphatides of plants and bacteria for comparative purposes only. Even with these severe restrictions, it will be possible to refer to no more than a small selection of the many important papers that have appeared on the subject during the past few years. 

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