Cytosine from uracil

N2O3 formed by a third order reaction, can deaminate DNA bases yielding uracil from cytosine, xanthine from guanine, methyl cytosine from thymine and hypoxanthine from adenine [ 56 ]. Furthermore, it can react with secondary amines to yield carcinogenic N-nitrosoamines, which can damage DNA by alkylation, [57]. 

Nucleosides Derived from Fluorinated Bases Many nucleosides have been synthesized from different fluoropyrimidines (uracil, thymidine, cytosine) or fluoropurine (adenine, guanine) bases, which are generally prepared by electro-... 

Ribonucleases are a widely distributed family of en-zymes that hydrolyze RNA by cutting the P—O ester bond attached to a ribose 5 carbon (fig. 8.12). A good representative of the family is the pancreatic enzyme ribonuclease A (RNase A), which is specific for a pyrimidine base (uracil or cytosine) on the 3 side of the phosphate bond that is cleaved. When the amino acid sequence of bovine RNase A was determined in 1960 by Stanford Moore and William Stein, it was the first enzyme and only the second protein to be sequenced. RNase A thus played an important role in the development of ideas about enzymatic catalysis. It was one of the first enzymes to have its three-dimensional structure elucidated by x-ray diffraction and was also the first to be synthesized completely from its amino acids. The synthetic protein proved to be enzymatically indistinguishable from the native enzyme. 

All of the direct fluorinations reported appear to be addition-elimination processes with solvent involvement (Scheme 42). A study of the mechanism and stereochemistry of uracil and cytosine fluorination using fluorine and acetyl hypofluorite has implicated a radical-cation mechanism (86JOC1466). The effect of acetate ion on the products proved to be important. In its absence both m-isomers (49) and trans-isomers (50) were observed in the reaction mixture, but only 50 [and 5-fluorouracil (51)] in its presence. The process has been rationalized in terms of the reaction diagram shown in Scheme 43. NMR studies have revealed that the acetate from the solution containing acetate ion, rather than the residue from acetyl hypofluorite, binds to the 6-position of uracil to form the intermediates (49 and 50). Acetate is a sufficiently strong base to induce trans-elimination of acetic acid from the cis-isomer (49). 5-Fluorouracil (51) was obtained in 45% yield from these reaction sequences (86CJC424). 

Figure 8.8 Synthesis of cytosine and uracil from simple organic molecules...

The four principal bases of the nucleic acids are uracil and cytosine, which are derivatives of pyrimidine, and adenine and guanine, which are derived from the purine heterocycle (Fig. 15.1). In the nucleic acids, ribose (in ribonucleic acid,... 

Chromatograms Obtained from Vacancy Development of a Mixture of Uracil, Hypoxanthine, Cytosine and Guanine... 

The biosynthesis of uracil proceeds via decarboxylation of orotidin-5 -phosphate, which is formed from carbamoyl phosphate and aspartate via orotate after nucleosidation with 5-phosphoribosyl-l-diphosphate. Uracil can also be generated from cytosine by oxidative deamination using sodium hydrogensulfite. 

Addition and elimination reactions of RS radicals derived from cysteamine and 2-mercaptoethanol involving C5-C6 double bond in various pyrimidines (thymine, uracil, and cytosine) were studied by the pulse radiolysis technique in aqueous solutions.For this purpose the kinetic parameters, i.e. the rate constants of the addition and elimination reactions, were determined using two chemical-monitoring systems. 

Figure 12.2 Onsets and peaks for the photoelectron spectra of the anion hydrates of cytosine, thymine, and uracil. From [24].

Pathways for pyrimidine catabolism. The major end product from cytosine and uracil is y6-alanine, from thymine it is jS-aminoisobutyrate. 

Lindahl T (1974) An N-glycosidase from Escherichia coli that releases free uracil from DNA containing deaminated cytosine residues. Proc Natl Acad Sci USA 71 3649-53... 

Deamination reaction converting cytosine to uracil. (B) Cytosine deamination, if not corrected, will result in a mutation from G-C to A-T after subsequent rounds of DNA... 

Figure 22.17 outlines the de novo and salvage synthetic pathways to thymine nucleotides. dUTP, an intermediate in the de novo pathways that begins with UDP, is readily recognized by DNA polymerases and can be incorporated into DNA in place of dXTP. The uracil from a dUMP residue in a DNA strand pairs with adenine (like thymine from a dXMP residue would), so there is no loss of or change in information in the DNA. However, dUMP residues can also arise from spontaneous deamination of dCMP. When this DNA is replicated, a mutation at the site will result because cytosine is meant to pair with guanine, not adenine. 

It is used to maximize the maintenance of the integrity of the information encoded by DNA. Cytosine can spontaneously deaminate to form uracil this damage is repaired by base excision repair. If uracil rather than thymine were used in DNA, then correctly positioned uracil would be indistinguishable from that arising from cytosine deamination. Use of thymine (methylated uracil) in DNA avoids this problem. 

We must now consider how the various "aquo species" interact with the DNA bases. So far, we have examined interactions of thymine, uracil and cytosine in detail and to a lesser extent with guanine. Reaction products from the aqueous solution produced by silver nitrate treatment of the chloride-complexes are complex mixtures, which is hardly surprising based on the known conq)lexity of the aqueous solution. It is possible to prepare monomeric (NHj)2 PtCbase " species similar to those obtained from the direct" reaction ot cis-PtCk (NH ) and the bases we assume they come from monomerxc aquo-complexes. 

Base excision is used to correct defects involving a single base. Figure 65.2 shows how the erroneous base uracil (derived from cytosine) is cleaved from the V C of deoxyribose by DNA glycosylase to leave an AP site (for structure of DNA, see Fig. 60.2). An AP site is a site without either a purine or a pyrimidine - described as apurinic or apyrimidinic . Alternatively, it is known as an abasic site . Then AP endonuclease cleaves the 5 C bond. This is followed by deoxyribose phosphate lyase that removes deoxyribose phosphate by cleaving the 3 C bond. Finally, the gap is filled by DNA polymerase and the nick is sealed by DNA ligase. 

Pyrimidine biosynthesis, de novo pyrimidine biosynthesis total synthesis of the pyrimidine ring of uracil, thymine, cytosine and their derivatives from carbamoyl phosphate and aspartate in all living cells. The pyrimidine ring of thiamin (vitamin Bj) has a different biosynthetic origin (see below). 

Deoxyuridine and thymidine are substrates for pyrimidine nucleoside phosphorylases, but deoxycytidine (and cytidine) is generally regarded as being inert to phosphorolysis (7) Tarris demonstration of deoxycytidine formation from cytosine in extracts of fish milt is an exception to this generalization (8). Catabolism of C3rtosine nucleosides is initiated by deamination to form uracil nucleosides which can be phosphorolyzed. 

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