Phosphoribosyl transferases ribonucleotide

Fig. 13.2. Synthesis of IMP. c = Hypoxanthine phosphoribosyl transferase (HPRT) GAR = glycinamide ribonucleotide FGAR = formyl glycinamide ribonucleotide PRPP = phosphoribosyl pyrophosphate AICAR = 5 aminoimidazole-4-carboxamide...

Fig. 2 Metabolism of 6-mercaptopurine (6-MP) via xanthine oxidase (XO) to the inactive metabolite 6-thiouric acid (6-TU), thiopurine S-methyltransferase (TPMT) to the inactive metabolite 6-methylmercaptopurine (6-MMP), and hypoxanthine guanine phosphoribosyl transferase (HPRT) to 6-thioinosine monophosphate (6-TIMP) which is then further metabolized to thioguanine nucleotides (6-TGN), 6-methylmercaptopurine ribonucleotides (6-MMPR) or 6-thio-inosine triphosphate (6-thio-ITP), these all being active metabolites...

ATP phosphoribosyl transferase ( ) pyropbospbohydrolase ( ) pbospboribosyl-AMP cyclohydrolase ( phosphoribosylfornumino-5-aminoimidazole-4-carboxamide ribonucleotide isomerase... 

FIGURE 48-2 Action of flucytosine in fungi. 5-Flucytosine is transported by cytosine permease into the fungal cell, where it is deaminated to 5-fluorouracil (5-FU). The 5-FU is then converted to 5-fluorouracil-ribose monophosphate (5-FUMP) and then is either converted to 5-fluorouridine triphosphate (5-FUTP) and incorporated into RNA or converted by ribonucleotide reductase to 5-fluoro-2 -deoxyuridine-5 -monophosphate (5-FdUMP), which is a potent inhibitor of thymidylate synthase. 5-FUDP, 5-fluorouridine-5 -diphosphate dUMP, deoxyuridine-5 -monophosphate dTMP, deoxyuridine-5 -monophosphate UPRTase, uracil phosphoribosyl transferase. 

Abbreviations not defined in text GCV, ganciclovir, ACV, acyclovir CPA, cyclophosphamide IFA, ifosfamide ThdPase, thymidine phosphorylase dFUr, 5 -deoxy-5-fluorouridine CK, deoxycytidine kinase ara-C, cytosine arabinoside CD, cytosine deaminase 5-FC, 5-fluorocytosine gpt, guanine phosphoribosyl transferase 6TX, 6-thioxanthine CB 1954, 5(-aziridine-l-yl)-2,4-dinitrobenzamide 5-FU, 6-fluorouracil MTX, methotrexate TMTX, trimetrexate Pgp, P-gylcoprotein AAG, 3-methyladenine DNA glycosylase Topo 1, topoisomerase I Topo 11, topoisomerase 11 ADH, aldehyde dehydrogenase BR, ribonucleotide reductase. 

Both ribose phosphate and an AMP moiety must be added to nicotinamide in order to convert it to NAD-I-. The ribose phosphate is derived from PRPP when a phosphoribosyl transferase catalyzes the formation of nicotinamide ribonucleotide or nicotinamide mononucleotide. The final step utilizes ATP, which serves as an adenyl donor for the formation of the dinucleotide NAD-l-. 

Purine bases can be converted to ribonucleotides via phosphoribosyl-transferases PP-ribose-P provides the ribosyl phosphate moiety. Purine nucleosides can be phosphorylated by ATP-requiring nucleoside kinases to form the same ribonucleotides. Finally, the possibility also exists that purine bases are first converted to ribonucleosides via nucleoside phos-phorylase, and then to ribonucleotides by the above-mentioned kinases. These routes of ribonucleotide synthesis are summarized as follows ... 

At the present time, we just report some experimental results of a study on the mechanism of action of allopurinol (U-hydroxy-pyrazolo (3, -d ) pyrimidine) and thiopurinol k thiopyrazolo (3, d) pyrimidine) on de novo biosynthesis of uric acid. In this present work, we have compared effect of alio and thiopurinol on oxypurine (xanthine and hypoxanthine) urinary excretion with their rate of synthesis of ribonucleotides in vitro by erythrocyte hemolysate in some particular enzymatic deficiencies (hypoxanthine-guanine phosphoribosyltransferase HGPRT, adenine phosphoribosyl-transferase APRT and xanthinuria). 

In our xanthinuric man activity of adenine and hypoxanthine -guanine phosphoribosyl transferase in erythrocytes is normal as well as rate or synthesis of ribonucleotide of alio and thiopuri-nol by hemolysate of erythrocytes but as we have shown, it is slow (about 1,5 to 2 of that of IMP). PRPP content of erytrocytes is also normal 6,70 nM/ml erythrocytes (mean s 6,6U 1,90 nM/ml erythrocytes). 

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