Cytidylic acid synthesis

The formation of cytidylic acid from uridylic acid was studied in a Novikoff hepatoma and E. colL In E. coli, glutamine appears to be the primary amino donor for cytidylic acid synthesis, and the synthesis occurs after uridylic acid has been converted to the triphosphate in the presence of ATP. The detailed mechanism of the amination of UTP to yield CTP... 

Phosphorylation of trityl-cytidine, followed by detritylation, allegedly gives cytidylic acid, but this synthesis merely indicates that cytidylic... 

Cytidylic acid, thymidylic acid, and uridylic acid (UMP) are compounds in which the sugar moiety of each of the related nucleosides described above is phosphorylated at the 5 position.The sugar moiety combined with the uracil base of the uridyHc acid used for RNA formation is D-ribose, whereas the sugar combined with the thymine of thymidylic acid used in DNA formation is D-2-deoxyribose. 2 -Deoxycytidyhc acid is used in RNA synthesis, whereas cytidyHc acid is used in the formation of DNA. 

Cytidine phosphates cytidine S -monophosphate (CMP, cytidylic acid, M, 323.2), cytidine 5 -diphos-phate (CDP, M, 403.19) and cytidine 5 -triphosphate (CTP, M, 483.16). For structure, see e. g. Pyrimidine biosynthesis. CTP is a precursor of RNA synthesis, while deoxy-CTP is a precursor of DNA synthesis. CDP may be regarded as the coenzyme of phospholipid biosynthesis (see Membrane lipids) (activated choline is CDP-choline). Glycerol and the sugar alcohol, ribitol, are also activated by bonding to CDP (see Nucleoside diphosphate sugars). Reduction of ribose... 

Since Hammarsten s results showed that not only the pyrimidines of PNA but also those of DNA were labeled after administration of labeled cytidine, it was concluded that this was indirect evidence for the conversion of a pyrimidine riboside to a pyrimidine desoxyriboside. The reason for this was that cytidine could not have been split to cytosine and then reincorporated into desoxycytidine, since it had been shown earlier that the free base, cytosine, could not be utilized for the synthesis of nucleic acid pyrimidines. The possibility should not be overlooked, however, that the above conversion may possibly occur at the nucleotide level thus, cytidylic acid, in which the phosphate is attached to the nucleoside, may be the intermediate in the transformation of PNA to DNA pyrimidines. 

Theoretically, it may be possible to artificially increase the production of interferon by the action of an inducer. Synthetic double-stranded ribonucleotide polymers, in particular the double-helical complex of polyinosinic acid with poly-cytidylic acid RNA (poly IC) are used in this way These agents activate the synthesis of interferon. They increase the resistance to viruses of cells m culture, and promote recovery in rabbits suffering from herpetic eye infection. This type of activity is an important prospect in the field of antiviral therapy. 

ATP is not the only reactive triphosphate. Other puriife or pyrimidine bases (guanine, cytosine, hypoxanthine, uracil cf. Chapt. VII-1) may take the place of adenine in the molecule the corresponding triphosphates replace ATP in several metabolic reactions. We will mention two examples The uridylic acid system in the interconversion of carbohydrates and the cytidylic acid system in the synthesis of phosphatides. 

Mercapto- 5-SH)-polycy tidy lie acid has been shown by Bardos et al.55 to block the DNA-directed RNA synthesis at 1/2 to 1/50 of the concentration of the unmodified DNA template used in the reaction. This mercapto derivative of polycytidylic acid (MPC) has been prepared by partial thiolation of polycytidylic acid (PC) according to the general procedure of Bardos et al.56> 57> the thiolated compound was gel-filtered through a Sephadex column and subsequently, through an Agarose-1.5 m (Bio-Gel A-l.5 m, exclusion limit 1,5000.000 mol. wt., Bio-Rad Labs.) column, then lyophilized and redissolved in 0.1 M Tris-buffer58). This compound (conversion of 9.5% of the cytidylate units to 5-mercaptocytidylate) was studied in the DNA-polymerase system of oncorna viruses. 

Phosphatidic acid is a branch point between the synthesis of fats and other glycerophospholipids. The high energy anhydride bond between the cytidylic and phosphatidic acid in CDP-diacylglycerol provides an activated intermediate for addition of polar head groups on the phosphate. 

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