Hypoxanthine phosphoribosyltransferase 1

Smith, D. W. and Friedmann, T. Characterization of the dopamine defect in primary cultures of dopaminergic neurons from hypoxanthine phosphoribosyltransferase knockout mice. Mol. Ther. 1 486-491,2000. 

HPRT hypoxanthine phosphoribosyltransferase acidosis, and stroke-like episodes... 

Figure 38 Schematic of the active site of hypoxanthine phosphoribosyltransferase with bound phosphor-...

This enzyme [EC 2.4.2.8] (also known as hypoxanthine phosphoribosyltransferase, IMP pyrophosphorylase, transphosphoribosidase, and guanine phosphoribosyltransferase) catalyzes the purine salvage reaction of hypoxanthine with 5-phospho-a-D-ribose 1-diphosphate to... 

Miller AD, Jolly DJ, Friedmann T, Verma IM. 1983. A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT) Gene transfer into cells obtained from human deficient in HPRT. Proc Nat Acad Sci USA. 80 4709-4713. 

J., et al. (1989) Germ-line transmission of a planned alteration made in a hypoxanthine phosphoribosyltransferase gene by homologous recombination in embryonic stem cells. Proc Natl Acad Sci USA 86, 8927-8931. 

Azaguanine brought about a 60% increase in the lifespan of mice with leukemia L1210. However, its ribonucleoside was inactive because it did not become phosphorylated, whereas 8-azaguanine was transformed by HPRT (hypoxanthine phosphoribosyltransferase) into its nucleotide, which RNA can incorporate." On the other hand, 8-azaadenosine" and 8-azainosine (9-ribofuranosyl-8-azahypoxanthine)," " both of which dis-... 

Figure 43-2 Simplified scheme of the metabolism of azathioprine and 6-mercaptopuHne to 6-thioguanine nucleotides (TGNs). TPMXThiopurine S-methyitransferase XO, xanthine oxidase HPRT hypoxanthine phosphoribosyltransferase. (Redrawn from Clunie GP, Lennard L Relevance of thiopunne methyltransferase status in rheumatology patients receiving azathioprine. Rheumatology (Oxford) 2004 43 13-8. Reproduced by permission from Oxford University Press.)...

W.M. (2003) Mutations induced by (-)-anti-llR,12S-dihydrodiol 13 S,1477-epoxide of dibenzo[a,7]pyrene in the coding region of the hypoxanthine phosphoribosyltransferase (Hprt) gene in Chinese hamster V79 cells. Environ. Mol. Mutagen., 41, 131-139. 

The crystal structure of hypoxanthine phosphoribosyltransferase has been solved in a ternary complex of the enzyme with the substrate 5-phosphoribosyl 1-pyrophosphate (PRPP) and an analogue of hypoxanthine with a carbon atom in place of As with PNP and OPRTase, these structures showed many contacts with... 

Examination of the urine of patients with this disease reveals in addition to the high uric acid an elevated hypoxanthine to xanthine ratio (L4). Furthermore, it was found that upon the administration of allopuri-nol, an inhibitor of xanthine oxidase that is widely used in the treatment of gout, the total output of purine is not reduced. This is in contrast to the reduction in total oxypurine output seen in normal or most gouty individuals. In addition, the ratio of hypoxanthine to xanthine is not reduced i.e., Lesch-Nyhan patients still maintained elevated hypoxanthine to xanthine ratios. These data have suggested an interference with hypoxanthine metabolism or reutilization, since the reduction in purine output after aUopurinoI therapy is due to anabolism of the hypoxanthine to inosinate (B4). It was shown by Seegmiller and his associates that there was an absence of hypoxanthine phosphoribosyltransferase in the red cells of subjects with Lesch-Nyhan syndrome. 

Levine and Taylor (78) have isolated a double mutant of E. coli, blocked in the salvage pathways leading to GMP, that is extremely sensitive to exogenous adenine (78, 128). This strain was missing both hypoxanthine phosphoribosyltransferase and guanine phos-phoribosyltransferase. Two classes of adenine-resistant, second-site revertants were isolated. One class was blocked at the adenine phosphoribosyltransferase reaction and thus could not convert adenine to AMP 128). Therefore, the toxicity was mediated through AMP. The other class represented purR cells, which constitutively expressed the de novo pathway. 

Since a recombination event between two loxP sites some distance apart or positioned on different chromosomes, is relatively rare, presumably because of physical constraints, a reflection of chromosome architecture and decreased proximity, such strategies are designed incorporating a binary positive selection system that is only activated after a successful recombination recreates the cassette. Thus, the desired recombination event will reconstruct the selectable genetic marker, from two silent portions placed adjacent to each of the loxP sites. The most commonly used selection systems include the reconstitution of a human hypoxanthine phosphoribosyltransferase (HPRT) minigene (16-20), or the juxtaposition of a strong promoter upstream of a selectable marker. 

Tissue Distribution or Hypoxanthine Phosphoribosyltransferase in Different Species... 

A separate xanthine phosphoribosyltransferase has been shown to be present in Salmonella typhimitrium (34, 4 ) uud in L. casei (36). Krenitsky et al. (36) have also recently demonstrated that in Escherichia ccli there is a separate hypoxanthine phosphoribosyltransferase, and that guanine and xanthine phosphoribosyltransferase activities are present in a sii e enz3rme. 

B. Watson, I.P.Gormley, S. E, Gradiner, H. J. Evans, and H. Harris, Reappearance of murine hypoxanthine phosphoribosyltransferase activity in mouse A9 cells after attempted hybridization with human cell lines, Exptl. Cell Res. 75 401 (1972). 

G. Milman, E. Lee, G. S. Ghangas, J. R. McLaughlin, and M. George, Jr., Analysis of HeLa cell hypoxanthine phosphoribosyltransferase mutants and revertants by two-dimensional polyacrylamide gel electrophoresis Evidence for silent gene activation, Proc. Natl. Acad. Sci. U.S.A. 73, 4589-4593 (1976). 

The reactivation of rat hypoxanthine phosphoribosyltransferase was obtained in heterokaryons of rat hepatoma and human fibroblast cultures under the control of human chromosomes (Croce et al., 1973). 

---