Hypoxanthine guanine

This enzyme represents a principal route for the return, or salvage, of purines such as hypoxanthine, adenine, and guanine to the monophosphate level. The activity requires a metal, preferably magnesium. 

The activity for this study was obtained from the microorganism Dictyostel-ium discoideum. An S-100 supernatant solution was prepared and used throughout as the source of HGPRT activity. 

Nucleoside phosphorylase catalyzes the reversible conversion of a purine riboside such as inosine to a purine base such as hypoxanthine and ribose-1-phosphate. Free phosphate is also required as a substrate. 

The assay involves the separation of reactants by reversed-phase HPLC on a Cis (Partisil 5 ODS) column with a mobile phase of 0.02 F KH2P04 (pH 

The reaction was carried out in the following manner. Stock blood was transferred into test tubes, water was added, and the solution was frozen and thawed to lyse the cells. At zero time, excess xanthine oxidase was added as a coupling enzyme to convert all the hypoxanthine that was formed during the reaction to uric acid. The reaction was started by the addition of inosine in a phosphate buffer. 

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Scott et al. [12] provided some experimental evidence supporting equation (27). The mixture contained uracil, hypoxanthine, guanine and cytosine, each present in the mobile phase at a concentration of 14 mg/1. The column employed was Im long, 1.5 mm I.D., packed with a pellicular cation exchange resin and operated at a flow rate of 0.3 ml/min. 

Lesch-Nyhan syndrome, an overproduction hyperuricemia characterized by frequent episodes of uric acid hthiasis and a bizarre syndrome of self-mutilation, reflects a defect in hypoxanthme-guanine phosphoribo-syl transferase, an enzyme of purine salvage (Figure 34—4). The accompanying rise in intracellular PRPP results in purine overproduction. Mutations that decrease or abohsh hypoxanthine-guanine phosphoribosyltrans-ferase activity include deletions, frameshift mutations, base substitutions, and aberrant mRNA splicing. 

Hypoxanthine-guanine Xq26-q27 Lesch-Nyhan syndrome... 

P5. Patel, P. I., Caskey, C. T., and Chinault, C. A., Fine structure of the human hypoxanthine guanine phosphoribosyltransferase gene. Mol. Cell. Biol. 6,393-403 (1986),... 

In the early days of meteorite analysis, it was difficult to detect N-heterocycles later, the Murchison meteorite was shown to contain xanthine, hypoxanthine, guanine, adenine and uracil (about 1.3 ppm in total). This meteorite seems to contain various classes of basic and neutral N-heterocycles, as well as isomeric alkyl derivatives. 

The free bases of the purines can be salvaged to spare de novo synthesis. The only hard thing is remembering what the names stand for. HGPRTase is hypoxanthine-guanine phosphoribosyltransferase, and it makes both IMP and GMP. A separate enzyme exists for the salvage of adenine. The salvage pathways are included in Fig. 19-1. 

The answer is c. (Katzung, p 933.) Resistance to thioguanine occurs because of an increase in alkaline phosphatase and a decrease in hypoxanthine-guanine phosphoribosyl transferase. These enzymes are responsible, respectively, for the increase in dephosphorylation of thiopurine nucleotide and the conversion of thioguanine to its active form, 6-thioinosinic acid. 

Puig, J. G., Torres, R. J., Mateos, E A. et al. The spectrum of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Clinical experience based on 22 patients from 18 Spanish families. Medicine (Baltimore) 80 102-112,2001. 

EphR erythropoietin-producing hepatocellular receptor HGPRT hypoxanthine-guanine phosphoribosyltransferase... 

There was no increase in mutation frequency at the hypoxanthine-guanine phosphoribosyl transferase gene locus in the presence or absence of S9 (Bootman et al. 1988b), and results were negative in a DNA repair assay with E. coli (Hodson-Walker and May 1988). 

Hsie, A.W., Brimer, P.A., Mitchell, T.J. and Gosslee, D.G. (1975). The dos-response relationship for ethyl methane sulfonate-induced mutation at the hypoxanthine-guanine phosphor-ibosyl transferase locus in Chinese hamster ovary cells. Somatic Cell Genet. 1 247-261. 

DNA = Deoxyribonucleic acid HGPRT = hypoxanthine-guanine phosphoribosyl transferase RNA = Ribonucleic acid -= negative result + = positive result (+) = weakly positive result... 

Brimer PA, Tan EL, Hsie AW. 1981. Effect of metabolic activation on the mutagenicity and cytotoxicity of ethylene dibromide in the Chinese hamster ovary hypoxanthine guanine phosphoribosyl transferase [Abstract]. Environ Mutagen 3 317-318. 

In many cells, the capacity for de novo synthesis to supply purines and pyrimidines is insufficient, and the salvage pathway is essential for adequate nucleotide synthesis. In patients with Lesch-Nyhan disease, an enzyme for purine salvage (hypoxanthine guanine phosphoribosyl pyrophosphate transferase, HPRT) is absent. People with this genetic deficiency have CNS deterioration, mental retardation, and spastic cerebral palsy associated with compulsive self-mutilation, Cells in the basal ganglia of the brain (fine motor control) normally have very high HPRT activity. These patients also all have hyperuricemia because purines cannot be salvaged. 

Fig. 13.1 Pathways of thiopurine metabolism. The positions of two polymorphically expressed enzymes, TPMT (thiopurine methyl transferase) and ITPA (inosine triphosphate pyrophosphatase), are shown. HGPRT, hypoxanthine guanine phosphoribosyl transferase 6-TIDP, 6-thioi-nosine diphosphate 6-TIMP, 6-thioinosine monophosphate 6-TITP, 6-thio inosine trinophosphate...

Deficiencies of adenosine deaminase and hypoxanthine-guanine phosphoribosyltransferase or a low activity of thymi-dylate synthase are responsible for clinical disorders. 

Lesch-Nyhan syndrome A deficiency of hypoxanthine-guanine phosphoribosyltransferase results in accumulation of purine bases (Chapter 10). This causes a marked increase in the plasma level of uric acid, and hence can give rise to gout, but it also causes a severe neurological disorder, known as Lesch-Nyhan syndrome, the symptoms of which include... 

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