Pyrimidine nucleoside phosphorylases,

Cytidine so formed is converted to uridine by cy-tidine aminohydrolase, while uridine and thymidine are converted to free bases by pyrimidine nucleoside phosphorylase. 

Pyrimidine bases are normally salvaged by a two-step route. First, a relatively nonspecific pyrimidine nucleoside phosphorylase converts the pyrimidine bases to their respective nucleosides (Fig. 41.17). Notice that the preferred direction for this reaction is the reverse phosphorylase reaction, in which phosphate is being released and is not being used as a nucleophile to release the pyrimidine base from the nucleoside. The more specific nucleoside kinases then react with the nucleosides, forming nucleotides (Table 41.2). As with purines, further phosphorylation is carried out by increasingly more specific kinases. The nucleoside phosphorylase-nucleoside kinase route for synthesis of pyrimidine nucleoside monophosphates is relatively inefficient for salvage of pyrimidine bases because of the very low concentration of the bases in plasma and tissues. 

Doxifluridine (5 -DFUR, 199) is an oral prodmg of 5FU (177). Compound 199, designed to circumvent the rapid degradation of 177 by dihydropyrimidine dehydrogenase in the gut wall, is converted into 177 by action of pyrimidine nucleoside phosphorylase. 

Further in vitro studies using a lung cancer cell line (A549) demonslrated that febuxostat (16 xM for 3h) completely inhibited xanthine oxidase activity without affecting the activities of adenosine deaminase, purine nucleoside phosphorylase, adenine phosphoribosyltransferase, hypoxanthine-guanine phosphoribosyltransferase, pyrimidine -nucleoside phosphorylase, or guanase. ... 

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. 

The method raising eiBciency of synthesis in recombinant Escherichia coli cells of pyrimidine nucleoside phosphorylase (PyrNPase) from... 

Transglycosylation of 2 -deoxy-2 -3H-uridine with 5-halouracils, catalysed by pyrimidine nucleoside phosphorylase, was used to prepare the labelled 2 -... 

A study of the mechanism of uracil incorporation into uridine phosphates was carried out in the Ehrlich ascites tumor, a tissue which utilized uracil as well as small molecule precimsors for nucleic acid formation (312). Uridine 5 -phosphate (UMP) was formed from uracil, ATP, and ribose 1-phosphate (R-l-P). Uridine was an intermediate in the formation of the nucleotide and was formed by the reaction of uracil and R-l-P with pyrimidine nucleoside phosphorylase (313, 314). Nucleoside kinase reacted the nucleoside with ATP to form UMP. The sequence is ... 

The biosynthesis of purines and pyrimidines is stringently regulated and coordinated by feedback mechanisms that ensure their production in quantities and at times appropriate to varying physiologic demand. Genetic diseases of purine metabolism include gout, Lesch-Nyhan syndrome, adenosine deaminase deficiency, and purine nucleoside phosphorylase deficiency. By contrast, apart from the orotic acidurias, there are few clinically significant disorders of pyrimidine catabolism. 

A class of compounds, called immucillins <2003BBR917>, are potent transition-state analogs of purine nucleoside phosphorylase. As such these pyrrolo[3,2-4 pyrimidines have been the target of much exploration. 

Ultraviolet (UV) spectroscopy does not tend to be the method of choice for structure determination, but a list of UV absorptions was given in the review by Knowles <1996CHEC-II(7)489>. Fluorescence properties and triplet yields of [l,2,3]triazolo[4,5-r/ pyridazines in various solvents have been reported <2002JPH83>. These heterocyclic systems were found to be photochemically very stable. In a recent paper, Wierzchowski et al. studied the fluorescence emission properties of 8-azaxanthine ([l,2,3]triazolo[4,5-r/ pyrimidine-5,7-dione) and its A -alkyl derivatives at various pH s <2006JPH276>. For the 8-azaxanthines, an important characteristic of emission spectra in aqueous solutions was the unusually large Stokes shift. Since 8-azaxanthine is a substrate for purine nucleoside phosphorylase II from Escherichia coli, the reaction is now monitored fluorimetrically. The fluorescence properties of [l,2,3]triazolo[4,5-r/ -pyrimidine ribonucleosides were earlier described by Seela et al. <2005HCA751>. 

Table 7.1.4 Concentration range of purine and pyrimidine metabolites in urine (pmol/mmol creatinine) from patients. ADA Adenosine deaminase, APRT adenine phosphoribosyltransferase, ASA adenylosuccinate lyase, DHP dihydropyrimidinase, DPD dihydropyrimidine dehydrogenase, HGPRT hypoxanthine-guanine phosphoribosyltransferase, PNP purine nucleoside phosphorylase, TP thymidine phosphorylase, UMPS uridine monophosphate synthase, / -UP fi-ureidopropionase... 

Pyrimidine nucleosides and their analogs as uridine phosphorylase inhibitors and potential chemotherapeutic agents 91CLY171. 

Nucleoside phosphorylase Purines + Pyrimidines Ribose I-phosphate... 

Nucleoside phosphorylases catalyze the reversible phosphorolysis in nucleosides and the transferase reaction involving purine or pyrimidine bases [42]. Scheme... 

Pyrimidines derived from dietary or endogenous sources are salvaged efficiently in mammalian systems. They are converted to nucleosides by nucleoside phosphorylases and then to nucleotides by appropriate kinases. 

Purine nucleosides are cleaved by the action of purine nucleoside phosphorylase with the liberation of ribose 1-phosphate (Kl, PI). The enzyme is apparently specific for purines. The material from erythrocytes catalyzes the phosphorolysis of purine but not pyrimidine nucleosides (T6.) Purine phosphorylase activity is found widespread in nature and in many animal tissues (FIO). Friedkin and Kalckar investigated an enzyme capable of cleaving purine deoxynucleosides to the aglycone and deoxy-ribose 1-phosphate. They concluded that the enzyme was identical to that which splits purine ribonucleosides (F8, F9). This enzyme is capable of degrading inosine, xanthosine, and guanosine to forms readily attacked by other enzymes. In so doing, it permits living cells to retain the ribose and deoxyribose moieties. 

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