Cytidine 3- , hydrolysis

Cytosine was isolated from hydrolysis of calf thymus in 1894 and by 1903 its structure was known and it had been synthesized from 2-ethylthiopyrimidin-4(3H)-one. The acid hydrolysis of ribonucleic acid gives nucleotides, among which are two cytidylic acids, 2 -and 3 -phosphates of cytidine further hydrolysis gives cytidine itself, i.e. the 1-/3-D-ribofuranoside of cytosine, and thence cytosine. The deoxyribonucleic acids likewise yield deoxyribonucleotides, including cytosine deoxyribose-5 -phosphate, from which the phosphate may be removed to give cytosine deoxyriboside and thence cytosine. 

If it is desired to isolate only the pyrimidine nucleosides, hydrolysis of the nucleic acid may be carried out in acid medium.6 This process, however, entails extensive deamination of cytidine to uridine. The pyrimidine... 

Cytidine 5 -phospho-A-acetylneuraminate (298), the coenzyme of sialyltransferases, is a sugar-nucleotide in which the leaving group is a nucleotidyl monophosphate that contains a carboxylate group directly attached to the anomeric centre. Studies of its hydrolysis reveal that at pH 5 specific acid catalysis occurs (Scheme 34) to yield a glycosyl carbocation as a tight ion pair, the lifetime of which was estimated... 

This enzyme [EC S.5.4.5], also called cytidine aminohy-drolase, catalyzes the hydrolysis of cytidine to produce uridine and ammonia. 

The structure shown was confirmed by the identification of cytidine 5 -phosphate and N-acetylneuraminic acid after mild acidic hydrolysis, and by the stability of the derivative on treatment with sodium borohydride. Comparison of the optical rotation of the starting derivative182 (44), the products of its hydrolysis,182 and the anomeric... 

A good source of uncommon bases is tRNA. It provides substrates for studying the effect of base on the rate of hydrolysis. Baev et al. (62) showed that V2-dimethylguanylyl-(3 -5 )-cytidine-3 phosphate (G2m-pCp) was hydrolyzed much slower than the usual GpCp. Venkstern (63) reported that Tp was hydrolyzed very slowly. Naylor et al. (64) found that Cp was hydrolyzed with half the rate of CpU. The same group of workers introduced (64, 65) a chemical block on uridine and pseudo-uridine residues by reacting RNA with l-cyclohexyl-3-(2-morpho-liny]-(4)-ethyl)-carbodiimide metho-p-toluene sulfonate. The modification of the uridine residues completely blocked the action of venom exonuclease and also blocked the action of pancreatic RNase. 

With cytidine cyclic phosphate as a substrate the step 2 process alone is measured. The procedure of Crook et al. (395) relies on the increase in absorbance at 286 nm which occurs on hydrolysis of the cyclic phosphate ring. Cleavage of the ring also results in proton release which is the basis of the titrimetric procedure described by Stark and Stein (132). The assays employing C>p are usually carried out in 0.35 M NaCl. The ionic strength for maximum activity is much higher for this substrate than for RNA. A brief summary of the above procedures is given by Klee (396). 

The pyrimidine nucleosides from ribonucleic acid (uridine and cytidine) present a more formidable problem, since they cannot be hydrolyzed by dilute mineral acid, and the use of concentrated acid usually destroys the sugar moiety. It was observed, however, that simultaneous bromination, hydrolysis, and oxidation of cytidine (with bromine-hydrobromic acid) yields 5-bromouracil plus D-ribonic acid.60 Since cytidine can be deaminated to uridine with nitrous acid,61 both of these pyrimidine nucleosides must... 

More difficulty was encountered with the pyrimidine deoxynucleosides. It was tacitly assumed that the sugar radical in thymidine and deoxy-cytidine, by analogy with the ribonucleosides, is attached to position Nl. The first significant experiment111 to shed some light upon the validity of this assumption was based upon the methylation studies of Levene and Tipson.108 Deoxyribonucleic acid from thymus was methylated with dimethyl sulfate plus alkali, and the product was degraded by strong-acid hydrolysis. One of the products obtained was 3-methylthymine (XI).111 A... 

Frick, L., Mac Neela J.P., and Wolfenden, R. 1987. Transition state stabilization by deaminases. Rates of nonenzymic hydrolysis of adenosine and cytidine. Bioorg. Chem. 15 100-108. 

Figure 9. Proposed transition state in the ribonuclease A-catalyzed hydrolysis of cytidine 2 -3 -phosphate. Two histidine residues of the enzyme participate in catalysis.

Acid hydrolysis of cytidine ribitol pyrophosphate led to a series of products, depending on the conditions of hydrolysis. L-Ribitol 1-phosphate (n-ribitol 5-phosphate), isomeric ribitol phosphates formed by acid-catalyzed migration of the phosphate group from the terminal position, and 1,4-anhydro-DL-ribitol were isolated. 

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