Cytidine diphosphate diglyceride

Raetz, C.R., Kennedy, E.R Function of cytidine diphosphate-diglyceride and deoxycytidine diphosphate-diglyceride in the biogenesis of membrane lipids in Escherichia coll. J Biol Chem 248 (1973) 1098-1105. 

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 reaction is freely reversible and the enzyme catalyzing it has been called DPN pyrophos-phorylase. This transfer of one 5 -nucleotide to another produces a pyrophosphate bond between them. The reaction is the prototype of a large number of such nucleotidyl transfers to other phosphate compounds. These include transfers to various sugar phosphates to form the nucleoside diphosphate sugar coenzymes, to choline phosphate to form C3fiidine diphosphate choline, and to phosphatidic acid to form cytidine diphosphate diglyceride. This nucleotidyl transfer is the protot)q)e also for transfers of nucleotides to produce mixed acid anhydrides with fatty acids, amino acids, and sulfates. In each instance inorganic pyrophosphate is produced this is also true of the nucleotidyl transfers which produce RNA and DNA. 

In the natural synthesis of phosphatidyl choline, the first step is believed to be the phosphorylation of choline, which itself has strongly basic properties of a tetraalkylammonium hydroxide. This is followed by reaction with cytidine triphosphate to give cytidine diphosphate choline, which in tnrn reacts with 1,2 diglyceride which is present (11.101). 

The nucleotide coenzymes are structurally related to the mononucleotides. Typical nucleotide coenzymes are adenosine triphosphate (ATP), flavin-adenine-dinucleotide (FAD) and numerous other phosphate esters of complex structure, containing adenosine, guanosine, cytidine or uridine. Five coenzymes are known for example, which are derived from cytidine diphosphate (CDP) CDP-choline, CDP-ethanolamine, CDP-diglyceride, CDP-glycerol and CDP-ribitol. 

Both the a,/3-diglyceride and the phosphatidic acid may be used for the synthesis of phospholipids. The choline and ethanolamine required respectively for the synthesis of lecithins and cephalins must be available in an active form as their cytidine diphosphate derivatives. 

These finding brought triglyceride synthesis in line with the synthesis of phospholipids, which was shown by Smith et al. (1957) to proceed by removal of the phosphate from phosphatidic acid, with the formation of an a )3-diglyceride. Diglyceride can now be converted into phospholipid, by cytidine-diphosphate-choline or ethanolamine (Kennedy and Weiss 1956) or into neutral triglycerides by the addition of one more fatty acid, derived from fatty acyl-coenzyme A. (Weiss and Kennedy 1956, 1960). 

Gurr, M. I., and G. Hubscher Cytidine diphosphate choline 1,2-diglyceride choline-phosphotransferase in intestinal mucosa. Biochem. J. 92, lOP (1964). 

S. W. Smith, and E. P. Kennedy The enzymatic formation of lecithin from cytidine diphosphate choline and D-1,2-diglyceride. J. biol. Chem. 231, 53—64 (1958). 

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 ... 

Cytidine diphosphate choline now is able to transfer phosphocholine onto the other alcohol components, the diglyceride cytidine monophosphate (CMP) is released and rephosphorylated to CTP by ATP. The formation of lecithin thus demands relatively much ATP at times the organism seems to waste its energy-rich phosphates. 

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