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Hypoxanthine ribosyl

Hirsch, and A.W. Hsie. A quantitative assay of mutation induction at hypoxanthine-guanine phospho-ribosyl transferase locus in Chinese hamster ovary cells (CHO/HGPRT system) Development and definition of the system. Mutat. Res. 45 91-101, 1977. [Pg.279]

Stereochemical Configuration. Deamination by means of nitrous acid transforms adenosine into inosine (ribosyl-hypoxanthine), and guanosine into xanthosine (ribosyl-xanthine). These four purine nucleosides are hydrolyzed rapidly, and with equal ease, by dilute mineral acids. They are also all hydrolyzed by the same enzyme, so it is reasonable to presume that they are similarly constituted as regards the stereochemical disposition at the sugar-base link. Whether this is of the a- or i8-configuration is still unknown. [Pg.199]

Bl. Bakay, B., and Nyhan, W. L., Heterogeneity of hypoxanthine guanine phospho-ribosyl transferase from human erythrocytes. Arch. Biochem. Biophys. 168, 26-34... [Pg.286]

Guanine + D-ribosyl phosphate guanosine -f- phosphate Hypoxanthine + D-ribosyl phosphate inosine + phosphate Hypoxanthine 2-deoxy- D-ribosyl phosphate 2-deoxyinosine + phosphate... [Pg.340]

Purine nucleoside phosphorylase (PNP). In contrast to lU-NH, PNP appears to use extensive contacts with the purine ring to promote catalysis and relatively few contacts with the ribosyl ring. The crystal structure of PNP has been determined in a complex with an iminosugar inhibitor, immucillin H, which was developed based on TS analyses of PNP-catalyzed hydrolysis and arsenolysis reactions. TS analysis revealed that the enzyme catalyzes a dissociative A Dn mechanism. The crystal structure was compared with the structures determined by Ealick and coworkers ° of PNP in a Michaelis complex analogue, PNP-inosine-sulfate, and a product complex, PNP-a-D-ribose-l-phosphate-hypoxanthine. [Pg.277]

Fig. 16 A schematic mechanism of PNP-catalyzed inosine phosphorolysis showing electrophile migration. This mechanism is based on cocrystal structures of PNP and TS analyses of inosine hydrolysis and arsenolysis. A large number of direct and water-mediated enzyme-substrate contacts hold the leaving group hypoxanthine and the nucleophile phosphate almost immobile while the ribosyl ring (the electrophile), because of the small number of contacts with the enzyme, is able to migrate from leaving group to nucleophile. Fig. 16 A schematic mechanism of PNP-catalyzed inosine phosphorolysis showing electrophile migration. This mechanism is based on cocrystal structures of PNP and TS analyses of inosine hydrolysis and arsenolysis. A large number of direct and water-mediated enzyme-substrate contacts hold the leaving group hypoxanthine and the nucleophile phosphate almost immobile while the ribosyl ring (the electrophile), because of the small number of contacts with the enzyme, is able to migrate from leaving group to nucleophile.
TS analysis of inosine hydrolysis. Experimental KIEs were determined for inosine hydrolysis under pre-steady state conditions because of the exceptionally slow dissociation of hypoxanthine (estimated K = 1.3 pM), which is rate-limiting under steady state conditions. Hypoxanthine binds to the other two PNP subunits with much lower affinity. KIEs in the ribosyl ring were typical of an AnDn mechanism. When the reaction was run in 20% methanol, the product ratio was 85 15 1-methylribose ribose. This is close to the ratio expected based on the relative nucleophilicities of MeOH and water, indicating that there is significant participation of the nucleophile in the reaction coordinate. As with the arsenolysis, the primary, 9- N KIE of 1.000 was anomalous. These KIEs were initially rationalized as indicating an internal equilibrium formation of ribose and hypoxanthine however, this is inconsistent with what is now known about the observable KIEs for stepwise reactions. [Pg.298]

HG-OES hydride generation optical emission spectrometry (see HG-AES) HGPRT-test hypoxanthine-guanine-phos-pho-ribosyl-transferase test, a mutagenicity test with mammalian cells HHPN hydraulic high pressure nebulizer HIV human immunodeficiency virus HMDE hanging mercury drop electrode... [Pg.1685]

Inosine can be converted directly to inosinate by inosine kinase. This enzyme has been shown to exist in human cells, but at a low level (P2). It undoubtedly does not play a major role. Inosine phosphorylase cleaves inosine to hypoxanthine and ribose I-phosphate (Kl). Inosine is formed by the deamination of adenosine catalyzed by adenosine deaminase, an enzyme found in varying concentrations in essentially all normal mammalian cells examined. Studies with an inhibitor of adenosine deaminase, ribosyl-4-amino-5-imidazole carboxamide, on several strains of Escherichia coli revealed a major role for the enzyme. In cells with a block in purine synthesis a condition of guanine deprivation occurred after growth with adenine as purine source, and there was a derepression of the enzymes that convert IMP to XMP and XMP to GMP (K17). [Pg.236]

The base is directly ribosylated with PRPP by PT. The two enzymes concerned with purine salvage are adenine phosphoribosyl transferase (APRT), which catalyzes the formation of AMP, and hypoxanthine-guanine phosphoribosyl transferase (HGPRT), which catalyzes the formation of GMP as well as IMP, the precursor of GMP and AMP (Figure 6.58). Purine nucleotide phosphorylases (PNPases) can also... [Pg.601]

The enhancement of ADPR-transferase activity is also an early consequence of drug-exposure and leads to defined changes in protein ADP-ribosylation, although the significance of these changes remains unclear at this time. The kinetics of cell death during exposure to methotrexate are similar when hypoxanthine is also present (when the activation of transferase is prevented but the basal activity is still present Fig. 2), or when SAB is present with the methotrexate. [Pg.331]

Friend et al. [1] made the striking observation that dimethyl sulfoxide (DMSO)-treated Friend erythroleukemia cells (FEE) differentiate in vitro. Subsequently, a number of other chemicals, including butyric acid,hypoxanthine andhexamethylene bis-acetamide were shown to induce Friend cells [2], These inducers appear to remove a block in the differentiation process but the mechanisms involved are unknown. The finding that benzamide and nicotinamide induced Friend cells [3, 4] suggested that since both compounds were inhibitors of poly(ADP-ribose) polymerase, poly(ADP-ribosylation) may have a role in the differentiation process. Furthermore, since poly(ADP-ribose) polymerase requires DNA strand breaks for activity [5], these observations implicated DNA strand breaks in FEE differentiation. [Pg.446]

For example, intact Ehrlich ascites tumor cells, or extracts therefrom, transfer the ribosyl group of uridine to hypoxanthine and thereby catalyze the net synthesis of inosine this reaction depends upon the coupled actions of uridine phosphorylase and purine nucleoside phosphorylase (89). Similar ribosyl transfers have been demonstrated with bacterial cells and extracts. Krenitsky has studied the kinetics of exchange between uracil-2- C and nonisotopic uridine catalyzed by highly purified uridine phosphorylase (30) ... [Pg.197]

Approaches to nucleoside synthesis by additions to suitably activated N-glycosides continue to receive attention. Ribofuranosyl purines have been prepared by addition of the imidazole derivative (7) to the glycosyl iminoether (8). Both a- and /3-ribosyl hypoxanthines and the corresponding 6-thio analogues were prepared in this manner. Addition of diketene to the amino-oxazoline derivative (9) gave a cyclonucleoside which was hydrolysed to the nucleoside analogue (10). Cyclization of ribopyranosyldiaminomaleonitrile... [Pg.158]


See other pages where Hypoxanthine ribosyl is mentioned: [Pg.378]    [Pg.368]    [Pg.133]    [Pg.378]    [Pg.368]    [Pg.133]    [Pg.646]    [Pg.309]    [Pg.249]    [Pg.1582]    [Pg.646]    [Pg.229]    [Pg.585]    [Pg.1385]    [Pg.48]    [Pg.59]    [Pg.585]    [Pg.646]    [Pg.305]    [Pg.366]    [Pg.638]    [Pg.278]    [Pg.646]    [Pg.669]    [Pg.878]    [Pg.648]    [Pg.309]    [Pg.170]    [Pg.179]    [Pg.216]   


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