Search results for HPRT1

Showing 17 results out of 17

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Species

Types

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Protein (4 results from a total of 4)

Identifier: R-HSA-56639
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: HPRT1: P00492
Identifier: R-HSA-9734264
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: HPRT1: P00492
Identifier: R-HSA-9734286
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: HPRT1: P00492
Identifier: R-HSA-9734269
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: HPRT1: P00492

Complex (4 results from a total of 4)

Identifier: R-HSA-74208
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-9734275
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-9734271
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-9734280
Species: Homo sapiens
Compartment: cytosol

Set (1 results from a total of 1)

Identifier: R-HSA-9734267
Species: Homo sapiens
Compartment: cytosol

Pathway (2 results from a total of 2)

Identifier: R-HSA-9734281
Species: Homo sapiens
Compartment: cytosol
Normally in humans, guanine and hypoxanthine can be salvaged by conversion to GMP and IMP, catalyzed by HPRT1 (hypoxanthine guanine phosphoribosyltransferase). In the absence of HPRT1 activity, however, accumulated guanine and hypoxanthine are catabolized by XDH (xanthine dehydrogenase / oxidase) to urate (Fu & Jinnah 2012).
Identifier: R-HSA-9735804
Species: Homo sapiens
Compartment: cytosol
Metabolic reactions disrupted by deficiencies of ADA, APRT, HPRT1, and PNP are annotated here.

Reaction (5 results from a total of 5)

Identifier: R-HSA-74215
Species: Homo sapiens
Compartment: cytosol
Cytosolic hypoxanthine-guanine phosphoribosyltransferase (HPRT1) tetramer catalyzes the reactions of guanine or hypoxanthine with PRPP to form GMP ir IMP and pyrophosphate (Holden and Kelley 1978; Jolly et al. 1983).
Identifier: R-HSA-9748951
Species: Homo sapiens
Compartment: cytosol
6-mercaptopurine (6MP) can be metabolized via three competing pathways; oxidation by xanthine oxidase (XDH), methylation by thiopurine methyl S-transferase (TPMT) and conversion by hypoxanthine-guanine phosphoribosyltransferase (HPRT1).

Hypoxanthine-guanine phosphoribosyltransferase tetramer (HPRT1) catalyzes the transfer of phosphoribosyl from 5-phosphoribosyl 1-pyrophosphate (PRPP) to 6-mercaptopurine (6MP), to form 6-thioinosine 5’-monophosphate (6TIMP) (Krenitsky et al. 1969, Xu et al. 1997). This is the metabolic branch for the formation of the pharmacologically active 6-thioguanine nucleotides (6-TGNs).
Identifier: R-HSA-9734274
Species: Homo sapiens
Compartment: cytosol
Normally in humans, guanine and hypoxanthine can be salvaged by conversion to GMP and IMP, catalyzed by HPRT1 (hypoxanthine guanine phosphoribosyltransferase). In the absence of HPRT1 activity, however, accumulated guanine and hypoxanthine are catabolized by XDH (xanthine dehydrogenase / oxidase) to urate. Hundreds of variants in HPRT1 have been identified, associated with phenotypes ranging from Lesch-Nyhan Syndrome in individuals with little or no HPRT1 activity, to hyperuricemia and gout in individuals with higher levels of HPRT1 activity. Here, we have annotated the failure of normal guanine and hypoxanthine salvage reactions due to three missense mutant alleles of HPRT1, originally identified in patients with Lesch-Nyhan Syndrome (Davidson et al. 1989, Fujimori et al. 1992, Laróvere et al. 2007) and shown when expressed in vitro to encode proteins with no detectable catalytic activity (Fu & Jinnah 2012).
Identifier: R-HSA-9748991
Species: Homo sapiens
Compartment: cytosol
6-mercaptopurine (6MP) can be metabolized via three competing pathways; oxidation by xanthine oxidase (XDH), methylation by thiopurine methyl S-transferase (TPMT) and conversion by hypoxanthine-guanine phosphoribosyltransferase (HPRT1).

6-mercaptopurine (6MP) is subjected to high first-pass metabolism due to oxidation in intestinal cells and liver cells by xanthine oxidase (XDH) (Saksela & Raivio 1996, Yamaguchi et al. 2007, Choughule et al. 2014). This reaction produces an inactive metabolite 6-thiouric acid (6TU, via 8-OH-6MP), which is excreted in urine. Patients with low XDH expression can exhibit elevated levels of the toxic antimetabolite 6MP which might result in a higher risk of thiopurine-induced adverse effects (Ding et al. 2021).
Identifier: R-HSA-9748983
Species: Homo sapiens
Compartment: cytosol
6-mercaptopurine (6MP) can be metabolized via three competing pathways; oxidation by xanthine oxidase (XDH), methylation by thiopurine methyl S-transferase (TPMT) and conversion by hypoxanthine-guanine phosphoribosyltransferase (HPRT1).

6MP can be methylated to 6-methylmercaptopurine (6MeMP) by thiopurine methyltransferase (TPMT) (Weinshilboum et al. 1978). Although 6MeMP is an inactive metabolite, it is still capable of inhibiting purine biosynthesis (Hill & Bennett Jr 1980, Dervieux et al. 2001).

Genetic variability in TPMT enzyme activity is responsible for the majority of the individual differences observed in both the efficacy and toxicity of thiopurines. The TPMT gene exhibits more than 30 genetic polymorphisms that affect its enzymatic activity (Wang & Weinshilboum 2006, Colleoni et al. 2013). TPMT methylation competes with the activation pathway and influences the relative proportion of intracellular active 6-thioguanine nucleotides (6-TGNs) produced by a given individual. Patients with intermediate or absent TPMT activity can produce significantly higher concentrations of 6-TGNs, and can experience potentially life-threatening myelosuppression when treated with standard or even low dose therapy (Lennard & Lilleyman 1989, Lennard et al. 1989, Relling et al. 2011, Dean 2012).

Icon (1 results from a total of 1)

Species: Homo sapiens
Hypoxanthine-guanine phosphoribosyltransferase.
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