Diglyceride biosynthesis

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... 

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). 

Substituted pyridazinone herbicides directly inhibit photosystem II, chloroplast pigment biosynthesis, and membrane lipid biosynthesis. Depending on the substitution, pyridazinones can specifically inhibit the synthesis of linolenic acid in galacto-lipids and phospholipids preferentially alter the fatty acid composition of monogalactosyl diglycerides compared with digalactosyl diglycerides and cause a build-up of saturated fatty acids in the chloroplast membranes. 

Sastry and Kates (1966) showed the capability of cell-free preparations from spinach leaves to form PI from glycerol [ P]phosphate. Sumida and Mudd (1970a) used [ H]inositol and CDP-diglyceride-inositol phosphatidyl-transferase (E.C. 2.7.8.11) in a study of PI biosynthesis by cell-free preparations from cauliflower inflorescence, and 70% of the activity was recovered in the 18,000-g pellet, which was not further characterized, and 30% in the 18,000-g supernatant. The pH optimum of the reaction was 9, the for CDP-DG was 45 /xM, and the metal ion cofactor requirement was better satisfied by Mn + (optimum 1.5 mM) than by Mg " (saturation at 40 mA/). 

Recent work in the general field of lipid biochemistry has revealed that although the carbon skeleton of serine is extensively used in the biosynthesis of ethanolamine (and hence choline and acetylcholine), decarboxylation of free serine does not occurnor is the ethanolamine formed from serine found free. It appears that the hydroxyl group of serine is first esterified with phosphatidic acid by reaction with cytidine diphosphate diglyceride (Figure 21). Phosphatidyl... 

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. 

This establishes an intimate relationship between the biosynthesis of complex lipids and that of ternary lipids, in the first case, the reaction being between a 1, 2-diglyceride and cytidinediphosphatecholine and in the second case between the 1, 2-diglyceride and a coenzyme A activated fatty add. 

The D-a,/8-diglycerides are the naturally occurring diglycerides, found as hydrolysis products of phosphatidyl choline acted upon by phospholipase C (chapter IV, 2) or as intermediates in the biosynthesis of a number of glycero-phosphohpids and triglycerides. 

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) ... 

The plasmalogenic diglyceride, prepared enzymically by the action of phospholipase C on the choline-containing phospholipid of beef heart, is defined as a D-a,/5-diglyceride in which the ester at the cx -position is replaced by an imsaturated ether. The reaction is catalysed by a choline-phosphotransferase enzyme similar to the phosphorylcholine-glyceride transferase shown to participate in the biosynthesis of lecithin (Reaction 12). A similar reaction occurs in brain (McMurray 1964b). 

The finding of McMurray et al. (1957) that the addition of CTP increases the incorporation of inorganic P into the phosphatidyl inositol of brain preparations imphcated a cytosine nucleotide in the biosynthesis of this lipid. It is now believed that phosphatidyl inositol is formed by a phosphatidyltransferase reaction in which a phosphatidyl group is transferred to free myoinositol from CDP-diglyceride ... 

Sphingomyelin. Weiss and Kennedy (1956) have described the synthesis of lecithin from CDP-choline and a diglyceride. An analogous reaction was reported by Sribney and Kennedy (1958) to be involved in the biosynthesis of sphingomyelin. This reaction is formulated below ... 

Cytidine diphosphate is the coenzyme of phosphatide biosynthesis it ties together a diglyceride and phosphorylcholine. Cytidine triphosphate first binds choline phosphate through a high energy bond ... 

Studies to elucidate the biosynthesis of this glycohpid revealed that crude extracts of M. lysodeikHcus, when supplemented with GDP-mannose, catalyzed the formation of mannosylmannosyl diglyceride and two other mannose-containing hpids (Lennarz, 19W). Althou neither of the other two hpids was found in whole cells, it was possible to prepare by enzymatic means sufficient quantities for analysis. One of these compounds was shown to be 0-a-D-mannosyl-(l—> a ) diglyceride by analysis, and by comparison of the deacylation product with... 

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