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)

Cultured fibroblasts from patients with partial or complete deficiencies of enzymes involved in purine metabolism provide a model for investigating the biosynthesis, interconversion, and excretion of purine metabolites at the cellular level. Skin fibroblast cultures were derived from five patients with hypoxanthineguanine phosphoribosyltransferase deficiency, from five subjects with idiopathic overproduction gout, from one patient with adenosine deaminase deficiency, and from four control subjects. Purine excretion was measured by recovering labeled purines from the incubation medium of cells grown in the presence of 14C-formate. In general the patterns of purine excretion by these cultured cells resembled the urinary excretion patterns of the patients from whom they were derived.
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PMID:Purine excretion by cultured skin fibroblasts from patients with abnormal purine metabolism. 94 Sep 64

Extreme degrees of hypoxanthine phosphoribosyltransferase (HPRT) deficiency in man are associated with gross sex-linked neurological dysfunction, gout and urinary stones (the Lesch-Nyhan or 'complete HPRT-deficiency' syndrome). The less severe degrees of enzyme deficiency (sex-linked recessive gout and/or urolithiasis or the 'partial HPRT-deficiency' syndrome) may be associated with minor neurological manifestations. Whole body purine synthesis de novo is accelerated in both these groups of patients. A strain of mice with an experimentally produced mutation at the HPRT locus showed some residual 'apparent HPRT activity' in brain, liver, testicular, splenic, kidney and ovarian tissues but not in erythrocyte haemolysates. The mutation removes exons 1 and 2 of the coding region of the gene together with the promotor and about 10 kb of upstream sequence from the gene. It is therefore possible that the observed 'apparent HPRT activity' in these mice is due to the operation of an alternative metabolic pathway. Purine synthesis de novo was markedly accelerated in their brain, testicular, splenic and kidney tissues. It was not accelerated in the liver tissue of male mice hemizygous for the mutation and the degree of acceleration in the female homozygotes only just reached statistical significance at the p = 0.02 level. This observation casts doubt on the importance of modulations in the rate of hepatic purine synthesis de novo as a mechanism for maintaining a steady supply of purines for translocation to other organs.
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PMID:Purine synthesis de novo and salvage in hypoxanthine phosphoribosyltransferase-deficient mice. 209 36

Purine metabolism was studied in fibroblasts cultured from three patients with gout in an attempt to determine the biochemical bases of their disease. The rate of purine biosynthesis de novo was normal in one line of cells, but the rate of catabolism of adenine nucleotides to hypoxanthine and inosine was greatly increased. The rate of purine biosynthesis de novo was increased in two lines of cells, and this was associated with increased concentrations of 5-phosphoribosyl 1-pyrophosphate. Purine synthesis was also less sensitive than normal to feedback inhibition. The catabolism of inosinate synthesized de novo was increased.
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PMID:Variations in purine metabolism of cultured skin fibroblasts from patients with gout. 565 84

Purine nucleotide degradation refers to a regulated series of reactions by which human purine ribonucleotides and deoxyribonucleotides are degraded to uric acid in humans. Two major types of disorders occur in this pathway. A block of degradation occurs with syndromes involving immune deficiency, myopathy or renal calculi. Increased degradation of nucleotides occurs with syndromes characterized by hyperuricemia and gout, renal calculi, anemia or acute hypoxia. Management of disorders of purine nucleotide degradation is dependent upon modifying the specific molecular pathology underlying each disease state.
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PMID:Metabolic basis for disorders of purine nucleotide degradation. 626 3

1. Variables that affect the measurement of purine synthesis de novo in human lymphocytes were studied and a reliable method of measurement of purine synthetic activity in these cells was established. 2. Purine synthesis de novo was measured as the rate of incorporation of [14C] formate into alpha-N-formylglycinamide ribonucleotide when further steps in the biosynthetic pathway had been blocked by azaserine. Incubation was carried out in a synthetic medium with a high phosphate concentration (25 mmol/l). 3. Purine synthesis de novo was measured in lymphocytes obtained on several occasions both from control subjects and from patients with gout, particularly those who tended to overproduce urate as suggested by high values of urinary urate. 4. Lymphocytes obtained from each individual on different occasions showed considerable variations in purine biosynthetic activity. This variation was such that there was no difference between the mean values obtained for the gouty subjects and the control subjects. 5. No correlation was obtained between the mean purine synthetic activity de novo in lymphocytes and either the serum urate concentration or the 24 h urinary urate excretion on a purine-free diet. 6 Apart from those with recognized enzyme mutations, no subgroup of the gouty population has been demonstrated in whom isolated lymphocytes demonstrate an intrinsic abnormality of purine synthesis de novo.
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PMID:Purine synthesis de novo in lymphocytes from patients with gout. 711 83

In gout, an effective diet is important to avoid or to lower complications and expenses of drug treatment. Most important dietary measures are reduction of purine uptake and alcohol consumption and normalization of body weight. Purine content of food can be altered quantitatively and qualitatively by storage and cooking with consequences for digestion and absorption of purines. The modern concept of diet in gout takes into consideration the purine content of food per weight, per portion and per energy.
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PMID:[Diet therapy in gout]. 767 97

Purine metabolism disturbances which may be responsible for urate nephropathy were revealed in 35% of the examinees with arterial hypertension. Gout manifestations occurred in many of the above patients. Purine metabolism disturbances contribute much to progression of renal disorders and arterial hypertension, require early diagnosis and treatment. Urate symptoms may serve a primary diagnostic indication.
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PMID:[Urate nephropathy in patients with arterial hypertension]. 794 Mar 61

Purine nucleotide degradation during ethanol catabolism, inhibition of renal excretion of urate by lactic acid, and high purine content of certain kinds of beverage are responsible for the elevation of serum uric acid level following alcohol drinking. It is well documented that rapid consumption of ATP produces uric acid via purine nucleotide degradation. Since individuals with ALDH2*1 can catalyze ethanol readily, they consume large amount of ATP, and thus produce more hypoxanthine than those with ALDH2*2. Thus, daily drinker and heavy drinker tend to readily induce hyperuricemia after alcohol ingestion. A high purine content in beer may contribute to the increasing frequency of hyperuricemia. Restriction of any kind of alcohol beverages, especially beer, is necessary in the medical control of patients with gout or hyperuricemia.
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PMID:[Alcohol ingestion and hyperuricemia]. 897 22

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

In 1996, the need for the clinical guidelines for the management of hyperuricemia and gout was proposed of the consensus conference held at the 29th annual meeting of the Japanese Society of Purine and Pyrimidine Metabolism (president Yuji Matsuzawa). At the consensus conference, the following announcement was made. 1. Because the majority of patients with hyperuricemia are in the condition of multiple risk factor clustering syndrome, hyperuricemia per se should be counted as one of the typical lifestyle related diseases. 2. Medical management should be directed independently for the treatment of gouty arthritis and for control of the serum uric acid level. 3. The serum uric acid level should be taken into account as a possible cardiovascular risk factor. 4. Urine alkalization should be started if there is no symptom indicating hyperuricemia for the prophylaxis of urinary stones and renal dysfunction. 5. All the medical management should be considered under the consensus of the many expert physicians dealing with hyperuricemia and gout. This principal announcement was made by the consensus conference and the simple management recommendation of a 6-7-8 rule was proposed through the consensus of expert physicians. Recently, a guideline committee was organized in the Japanese Society of Gout and Nucleic Acid Metabolism (previous by the Japanese Society of Purine and Pyrimidine Metabolism) and the Guidelines for the Management of Hyperuricemia and Gout were prereleased in February and published in August 2002. In the new guidelines, the above policy was introduced and evidence was collected to give the guidelines contemporary clinical usefulness and value. It will help in the proper management of hyperuricemia in apparently healthy persons in occupational health, having multiple risk factors.
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PMID:[Management of hyperuricemia in occupational health: with reference to "guidelines for the management of hyperuricemia and gout"]. 1262 69


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