Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Different brain regions were removed post mortem from three patients with the Lesch-Nyhan syndrome and were examined for alterations in hypoxanthine-guanine phosphoribosyl transferase (HGPRT), adenine phosphoribosyl transferase, and biochemical indexes of norepinephrine, dopamine, serotonin, gamma-aminobutyric acid (GABA), and acetylcholine neuron function, as compared with age-matched controls. The level of HGPRT activity in the material from patients with the Lesch-Nyhan syndrome was less than 1 per cent of control levels, whereas adenyl phosphoribosyl transferase was not significantly altered. All biochemical aspects of the function of dopamine-neuron terminals in the striatum (except dihydroxyphenylacetic acid levels) were decreased to 10 to 30 per cent of the control values. Serotonin and 5-hydroxyindoleacetic acid levels were increased, striatal choline acetyltransferase levels were low, and striatal glutamic acid decarboxylase and guanylate cyclase activities were unaltered. The disruption of the balance between the functions of GABA, dopamine, and acetylcholine neurons in the extrapyramidal system probably accounts for some of the symptoms observed in the Lesch-Nyhan syndrome (e.g., choreoathetosis).
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PMID:Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome. 611 11

We have examined several aspects of neurotransmitter function in the brains of mice carrying a deletion mutation in the gene encoding the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). During the first 6 weeks of postnatal development, dopamine levels in whole-brain extracts from the mutant mice (HPRT-) failed to increase at rates comparable to normal animals, resulting in 40% lower dopamine levels throughout adulthood. Regional analysis in adult animals showed the caudoputamen to be the most severely affected region, with dopamine deficits of 48-64%. Dopamine levels in other regions were normal or less severely affected. The decrease in dopamine was accompanied by a decrease in tyrosine hydroxylase (TH) activity, the rate-limiting step in dopamine synthesis. Kinetic analysis of TH extracted from the caudoputamen of normal and HPRT- mice demonstrated a 45% decrease in Vmax with an increased affinity for the tetrahydropterin cofactor in the mutants. Labeling of midbrain dopamine neurons using TH immunohistochemistry revealed no obvious deficits in the number of midbrain dopamine neurons, but quantitative autoradiographic studies revealed significant reductions in the binding of 3H-N-[1-(2-benzo(beta)thiophenyl)cyclohexyl]piperidine (3H-BTCP) to dopamine uptake sites in the forebrain of the mutants. In contrast to these abnormalities of the dopamine systems in the mutant mice, other neurotransmitter systems appeared relatively unaffected. Norepinephrine, 5-HT, tryptophan hydroxylase, and glutamic acid decarboxylase were present at normal levels in the brains of the mutants. ChAT activity was slightly lower than normal in the caudoputamen of the mutant animals, but was normal in all other brain regions examined. These results indicate that HPRT deficiency is associated with a relatively specific deficit in basal ganglia dopamine systems that emerges during the first 2 months of postnatal development.
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PMID:Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease. 750 65