Phosphoribosyltransferase 9 Nucleoside Phosphorylase

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... 

The activity of hypoxanthine-guanine phosphoribosyltransferase, adenine phos-phoribosyltransferase, adenosine deaminase, and purine nucleoside phosphorylase can be determined in dried blood spots using an HPLC-linked assay [3]. 

Deletion of uridine kinase Deletion of nucleoside phosphorylase Deletion of orotic acid phosphoribosyltransferase Increased thymidylate kinase... 

Fig. 41.10. Salvage of bases. The purine bases hypoxanthine and gnanine react with PRPP to form the nucleotides inosine and gnanosine monophosphate, respectively. The enzyme that catalyzes the reaction is hypoxanthine-gnanine phosphoribosyltransferase (HGPRT). Adenine forms AMP in a reaction catalyzed by adenine phosphoribosyltransferase (APRT). Nucleotides are converted to nucleosides by 5 -nucleotidase. Free bases are generated from nncleosides by purine nucleoside phosphorylase. Deamination of the base adenine occurs with AMP and adenosine deaminase. Of the purines, only adenosine can be directly phosphorylated back to a nucleotide, by adenosine kinase.

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. ... 

Enhanced excretion of orotic acid was observed under different physiological [209,210] and nutritional [211-217] conditions. The amount of orotic acid excreted during human pregnancy is about 20-40 mg per day and does not vary substantially during the course of pregnancy [209,210]. Inherited deficiencies of the urea cycle [218], purine nucleoside phosphorylase [219], and especially of orotate phosphoribosyltransferase and orotidylic acid decarboxylase also result in an increased excretion of orotic acid. 

Pyrimidine ribonucleotides, like those of purines, may be synthesized de novo from amino acids and other small molecules (Chapter 11). Preformed pyrimidine bases and their ribonucleoside derivatives, derived from the diet of animals or found in the environment of cells, may be converted to ribonucleotides via nucleoside phosphorylases and nucleoside kinases. In some cells a more direct pyrimidine phosphoribosyltransferase pathway has also been recognized (Chapter 12). Ribonucleotides are catabolized by dephosphorylation, deamination, and cleavage of the glycosidic bond, to uracil. Uracil may be either oxidatively or reductively cleaved, depending on the organism involved, and can be converted to CO and NH (Chapter 13). 

HGPRT hypoxanthine guanine phosphoribosyltransferase deficiency PNP purine nucleoside phosphorylase deficiency... 

Thus the utilization of exogenous purine nucleosides involves three phosphoribosyltransferases and one nucleoside phosphorylase, if a phosphorolytic cleavage of the nucleosides is the first reaction to take place. An alternative pathway for the utilization of nucleosides would be a direct phosphorylation to monophosphates. The question is then Do such nucleoside kinases exist in E.coli,and if this is the case, how many enzymes are involved ... 

The presenee of various nueleoside phosphorylase, phosphotransferase and nucleoside kinase activities has been described (109,110). Phosphoribosyltransferase activity was found only for uracil and orotate. 

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