Cytidine nucleotides

Hg ", Zn ", Cd " ) light emission is shifted to the red (610—615 nm). In vitro a flash of light is produced (< 1 s) that decays rapidly. Glow-type emission is obtained ia the presence of detergents (Triton X-100), polymers (PEG 6000), coen2yme A, inorganic pyrophosphate, and cytidine nucleotides (206,207). 

Ford, S. R., Hall, M. S., and Leach, F. R. (1992). Enhancement of firefly luciferase activity by cytidine nucleotides. Anal. Biochem. 204 283-291. 

In higher eukaiyotes, most of the chromosomal DNA carries 5-methyl-cytidine residues located in CpG sequence motives. There is a close correlation between transcriptional inactivation and methylation. On the other hand, considerable evidence shows that regions of DNA that are actively engaged in transcription lack 5-methyl-cytidine nucleotides in CpG motivs. Hence DNA methylation is a means how cells regulate gene expression. DNA methylation which is catalyzed by DNA methyltransferases is the best characterized epigenetic mechanism. 

A classic description of the role of cytidine nucleotides in phospholipid synthesis. 

Dideoxyhexoses. Several bacterial antigenic determinants with the general structure of 3,6-dideoxyhexoses occur in the cell wall of Pasteurella and Salmonella strains. Most of the transformations reported so far occur as cytidine nucleotides (see Table I, References 15, 16, 17, 18, 19). Here, again the first step is the transformation of the cytidine diphospho-linked glucose into its corresponding 4-keto derivative. By at least two distinct steps, requiring NADPH, reduction to several different 3,6-dideoxyhexoses have been reported. One 3,6-dideoxyhexose CDP-tyvelose (3,6-dideoxy-D-arabino hexose) is formed by a specific 2-epimer-ase from CDP-paratose (24). 

Neglecting the variety of possible ionization processes for each component, the minimal mechanism for the interaction of cytidine nucleotides is shown in Fig. 24 and some related rates in Table XXVII. For each nucleotide there is a bimolecular step followed by an... 

The structures of these cytidine nucleotides were confirmed by synthesis. Condensation of 1,2-0-isopropylidene-L-glyceritol 3-phosphate with cytidine 5-phosphate in the presence of dicyclohexylcarbodiimide, followed by careful acid hydrolysis of the isopropylidene group, yielded cytidine glyceritol pyrophosphate identical with the natural product. 

Cidofovir (Figure 24.4) is an antiviral cytidine nucleotide analog with inhibitory activity against HCMV and other herpes viruses. Cidofovir is first converted to an active diphosphate form by cellular enzymes. Antiviral effects of cidofovir are due to inhibition of viral DNA polymerase by the diphosphate metabolite (Neyts and De Clercq, 1994 Plosker and Noble, 1999 Scholar and Pratt, 2000). The diphosphate probably interacts with DNA polymerase either as an alternate substrate (incorporation at the 3 end or within the interior of the DNA chain) or as a competitive inhibitor (with respect to the normal substrate dCTP). Cidofovir inhibits HCMV DNA synthesis at intracellular concentrations 1000-fold lower than are required to inhibit cellular DNA synthesis (Neyts and De Clercq, 1994). For HSV-1 and HSV-2 corresponding concentrations are at least 50-fold lower. 

Reaction of aspartic acid (14) with carbamoyl phosphoric acid (17) in the presence of the allosteric enzyme aspartate carbamoyltransferase (aspartate transcar-bamoylase) gives N-carbamoyl aspartic acid (18), which is cyclised to L-dihy-droorotic acid (19) by dihydroorotase. Oxidation of L-dihydroorotic acid by flavoprotein, orotate reductase gives orotic acid (20), which reacts with 5-phosphori-bosy 1-1-pyrophosphate (PRPP) in the presence of orotate phosphoribosyl transferase to form orotidine 5 -monophosphate (OMP, 21). Decarboxylation of OMP by orotid-ine 5 -phosphate decarboxylase yields uridine 5 -monophosphate (UMP, 22), which acts as precursor for the cytidine nucleotides (CTP) (Chart 6). 

Vacha J, Seifert J. 1977. Biosynthesis of cytidine nucleotides and levels of cytochrome p-450 in rat liver after administration of carbon tetrachloride. Toxicology 8 157-164. 

Cidofovir is an antiviral agent that inhibits viral DNA synthesis by interfering with viral DNA polymerase. It is indicated in the treatment of Cytomegalovirus retinitis in patients with AIDS. Cidofovir (l-[(5)-3-hydroxy-2-(phosphonomethoxy)-propyljcytosine dihydrate) is a cytidine nucleotide analog with inhibitory activity against human herpes, papilloma, polyoma, pox, and adenoviruses. 

Purine nucleotides, cytidine nucleotides, amino sugars, tryptophan, histidine... 

Consistent with the metabolic data, there is no dihydrofolate reductase/thymidylate synthase activity (75). Thymidine is salvaged by a phosphotransferase. Uracil PRTase, uridine phosphorylase, cytidine deaminase and uridine and cytidine phosphotransferases were found. The major pyrimidine salvaged is uracil via its PRTase. The lack of incorporation of salvaged uracil into DNA and the lack of thymidylate synthase indicates that this parasite cannot synthesize TMP from UMP. It is dependent on salvage for its thymidine requirements. This parasite possesses a hydroxyurea-resistant ribonucleotide reductase and can synthesize deoxycytidine nucleotides from cytidine nucleotides. 

Figure 8.12 Ribozyme. Hydrolysis reaction catalyzed by ribozyme that consists of an enzyme "E" strand and a substrate "S" strand. Hydrolysis takes place below a cytidine nucleotide, converting "S" into two product strands "PI" and "P2" that dissodate from the "E" strand.

It is an enzyme used in the early stages of cytidine nucleotide synthesis. 

Fig. 2. The pathway to phosphatidylcholine involving cytidine nucleotides (Kennedy, 1957).

Although the action of barbiturates on the biosynthetic chain to at least two phospholipids is apparently at a point subsequent to the phosphorylation of the base, an investigation of later stages (Fig. 2) proved difficult because of the low concentration of the cytidine nucleotides in the brain (Nelson and Barnum, 1960 Ansell and Bayliss, 1961). This investigation should be possible in vitro and has been carried out for chlorpromazine (Section III, B). Although no experiments have apparently been carried out on the effect of barbiturates on the biosynthesis of cytidine nucleotides in vitro, studies have been made on the transfer of P 2-orthophosphate to phospholipids. This transfer presumably involves cytidine nucleotides for certain phospholipids. Strickland (1954) found that 4 X 10 M Chloretone (l,l,l-trichloro-2-methyl-2-pro-... 

X 10— No effect on transfer of P -phos-phorylcholine and P 2-phospho-rylethanolamine from cytidine nucleotide complexes to phospholipids (Ansell and Marshall, 1963b)... 

A series of other barbiturates (phenobarbital, barbital, thiopental, pentobarbital at 1 mmol l i concentration inhibit the orotate uptake system without affecting the incorporation of uracil into cellular pyrimidines [287]. While barbituric acid and hexobarbital are less active, phenylethylhydan-toin, chlorpromazine and phenethyl alcohol are extremely active. Phenobarbital also depresses the utilization of orotic acid for the synthesis of cytidine nucleotides in the liver [288]. a-Hexachlorocyclohexane, an inhibitor of the phenobarbital type, was even more effective in depressing de novo cytidine nucleotide synthesis from orotic acid [289]. 

Seifert, J. and Vacha, J. Cytidine nucleotide biosynthesis and the level of c)dochrome P-450 in rat hver microsomes after administration of colchicine. Arch. Biochem. Biophys., 172, 106-109 (1976)... 

Seifert, J. and Vacha, J. Decreased utilization of orotic acid for the synthesis of cytidine nucleotides in rat hver after administration of a-hexychlorocyclohexane. Toxicology, 7, 155-161 (1977)... 

Biosynthesis of uridine and cytidine nucleotides. This is shown in Fig.l. The first pyrimidine nucleotide to appear de novo in this pathway is uridine 5 -mono-phosphate (UMP, uridylic acid). This is phosphoryla-ted to uridine 5 -triphosphate (UTP). By donation of an amino group from ammonia or glutamine (in animal tissues), UTP is converted to cytidine 5 -triphos-phate (CTP). 

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