Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rapid and selective reversed-phase high-performance liquid chromatographic method for the simultaneous determination of hypoxanthine and xanthine in biological fluids was developed. The identification of hypoxanthine and xanthine was confirmed by xanthine oxidase reaction. This method was applied to the investigation of purine metabolism in subjects with xanthine oxidase deficiency or gout. Hypoxanthine concentrations three to ten times higher than those determined in plasma were found in erythrocyte samples from normal subjects and from patients with xanthine oxidase deficiency or hyperuricemia under allopurinol therapy.
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PMID:High-performance liquid chromatographic determination of hypoxanthine and xanthine in biological fluids. 689 51

Primary gout is characterized by increased plasma and decreased urinary concentrations of hypoxanthine, xanthine and uric acid. To examine whether lead could explain the disturbance of purine metabolism in gout, we determined hypoxanthine, xanthine and uric acid metabolism and 5-day cumulative urinary lead excretion rates after an EDTA (calcium disodium edetate) test in 27 patients with primary gout and reduced creatinine clearance (C(cr)) and in 50 patients with gout and normal C(cr). The results were compared to those obtained in 26 normal subjects matched for age. All gout patients evidenced a marked renal underexcretion of hypoxanthine, xanthine and uric acid relative to their increased plasma levels. Purine metabolism was remarkably similar in both gout groups except for a significantly lower uric acid excretion in patients with reduced C(cr). Blood lead levels and cumulative lead excretion rates were significantly higher in gout patients with renal failure as compared to patients with normal C(cr). Fourteen patients (52%) with renal insufficiency and 6 (12%) with normal C(cr) showed increased lead excretion rates (95% Cl for the difference, 29-51%, p < 0.001). Mobilizable lead was not significantly correlated with serum or urinary purine concentrations. Hypoxanthine, xanthine and uric acid underexcretion was similar in gout patients with increased or normal cumulative lead excretion rates. The prevalence of atheromatosis and arterial hypertension together was significantly higher in gout patients with renal failure than in patients with normal C(cr) (81 vs. 60%, 95% Cl for the difference, 11-31%, p < 0.005). These results indicate that lead is not a significant contributor to the renal underexcretion of purines in gout. An increased mobilizable lead is not by itself evidence that lead is the cause of the renal insufficiency in patients with primary gout. Atheromatous nephropathy and/or nephroangiosclerosis may explain impaired renal function in patients with primary gout.
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PMID:Purine metabolism in patients with gout: the role of lead. 906 56

A modelling approach is used to analyse diseases associated with purine metabolism in man. The specific focus is on deficiencies in two enzymes, hypoxanthine:guanine phosphoribosyltransferase and adenylosuccinate lyase. These deficiencies can lead to a number of symptoms, including neurological dysfunctions and mental retardation. Although the biochemical mechanisms of dysfunctions associated with adenylosuccinate lyase deficiency are not completely understood, there is at least general agreement in the literature about possible causes. Simulations with our model confirm that accumulation of the two substrates of the enzyme can lead to significant biochemical imbalance. In hypoxanthine:guanine phosphoribosyltransferase deficiency the biochemical mechanisms associated with neurological dysfunctions are less clear. Model analyses support some old hypotheses but also suggest new indicators for possible causes of neurological dysfunctions associated with this deficiency. Hypoxanthine:guanine phosphoribosyltransferase deficiency is known to cause hyperuricaemia and gout. We compare the relative importance of this deficiency with other known causes of gout in humans. The analysis suggests that defects in the excretion of uric acid are more consequential than defects in uric acid synthesis such as hypoxanthine:guanine phosphoribosyltransferase deficiency.
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PMID:Analysis of abnormalities in purine metabolism leading to gout and to neurological dysfunctions in man. 944 73

Hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficiency is an X-linked defect of purine metabolism. Clinical manifestations are usually related to the degree of enzyme deficiency; complete HPRT deficiency (Lesh-Nyhan Syndrome) presenting with severe neurological or renal symptoms, or partial HPRT deficiency (Kelley-Seegmiller syndrome) manifesting as a gout-urolithiasis syndrome. We report a case of partial HPRT deficiency presenting as chronic tophaceous gout, mental retardation, nephrolithiasis and family history suggestive of X-linked inheritance, for its rarity.
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PMID:Partial HPRT deficiency (Kelley-Seegmiller syndrome). 1664 40

Gout and pain are synonymous, and a study in this issue of the BJP reports a novel anti-nociceptive effect of allopurinol, the drug most commonly used to treat gout. Allopurinol works by inhibiting xanthine oxidase (XO), the enzyme responsible for converting hypoxanthine to uric acid which is deposited as crystals in the joints of gout sufferers. Hypoxanthine is a metabolite of, and a possible precursor to, adenosine. Schmidt et al., find that acute inhibition of XO with allopurinol produces a modest adenosine A(1) receptor-mediated anti-nociceptive effect in common tests of chemical and thermal nociception in mice. A concomitant increase in cerebrospinal fluid levels of adenosine supports their hypothesis that inhibiting XO increases adenosine levels via salvage from hypoxanthine. Elevating endogenous adenosine levels by inhibiting metabolism is a well-established strategy for producing anti-nociception in many preclinical models, but inhibiting XO is likely to be particularly beneficial in some chronic pain states because of the pro-nociceptive reactive oxygen species that are produced by XO activity. Thus, allopurinol may have unexpected benefits in pain associated with chronic inflammation, diabetes and vascular dysfunction.
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PMID:Allopurinol for pain relief: more than just crystal clearance? 1913 97

Mutations in Hypoxanthine-guanine Phosphoribosyltransferase1 (HPRT1) gene can lead to metabolic disorder of hypoxanthine and guanine metabolism, and other severe symptoms such as hypophrenia, gout, and kidney stones, called the Lesch-Nyhan disease (LND). Although the mutations are widely distributed throughout the HPRT1 gene, there are some isolated hot spots. In this study, we aim to introduce two previously reported hot spots, c.508 C>T and c.151 C>T, which could lead to premature translational termination in HPRT1 gene. Through CRISPR/Cas9 mediated homology-directed repair (HDR) by using single-stranded oligo-deoxyribonucleotides (ssODN) as donor template, we obtained cell clones containing these two mutations in HEK293T or HeLa cells. Targeted mutation of c.508 C>T and c.151 C>T reached to 16.3% and 10%, respectively. We further detect HPRT1 protein levels with Western blot and enzyme activity with 6-TG in 5 different cell clones. HPRT1 protein and its enzymatic activity both was hardly detected in homozygous mutant cells, while reduced HPRT1 protein expression and enzymatic activity was detected in heterozygous mutant cells. Our study will be beneficial to those who working on generation of cell or animal models of HRPT1 mutations, and provides a basis for further investigations on the genetic mechanism of Lesch-Nyhan disease.
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PMID:[Generation of cell strains containing point mutations in HPRT1 by CRISPR/Cas9]. 3162 56