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)

THE CONCEPT OF AN ABNORMALITY OF GLUTAMINE METABOLISM IN PRIMARY GOUT WAS FIRST PROPOSED ON THE BASIS OF ISOTOPE DATA: when [(15)N]glycine was administered to gouty subjects, there was disproportionately great enrichment of N-(3 + 9) of uric acid, which derive from the amide-N of glutamine. An unduly high concentration of (15)N in glutamine was postulated, and attributed to a hypothetical defect in catabolism of glutamine. Excess glutamine was proposed as the driving force of uric acid overproduction. WE HAVE REEXAMINED THIS PROPOSITION IN FOUR GOUTY SUBJECTS: one mild overproducer of uric acid with "idiopathic gout," one marked overproducer with high-grade but "partial" hypoxanthine-guanine phosphoribosyl-transferase deficiency, and two extraordinary overproducers with superactive phosphoribosylpyrophosphate synthetases. In the last three, the driving force of excessive purine biosynthesis is a known surplus of alpha-5-phosphoribosyl-1-pyrophosphate. Disproportionately high labeling of N-(3 + 9) was present in all four gouty subjects, most marked in the most flamboyant overproducers. The precursor glucine pool was sampled by periodic administration of benzoic acid and isolation of urinary hippuric acid. Similarly, the precursor glutamine pool was sampled by periodic administration of phenylacetic acid and isolation of the amide-N of urinary phenylacetylglutamine. The time course of (15)N enrichment of hippurate differed from that of the amide-N of glutamine. Whereas initial enrichment values of hippurate were very high, those of glutamine-amide-N were low, increasing to a maximum at about 3 h, and then declining less rapidly than those of hippurate. However, enrichment values of hippurate and of phenacetyl glutamine were normal in all of the gouty subjects studied. Thus, preferential enrichment of N-(3 + 9) in gouty overproducers given [(15)N]glycine does not necessarily reflect a specific abnormality of glutamine metabolism, but rather appears to be a kinetic phenomenon associated with accelerated purine biosynthesis per se.In addition, greater enrichment of N-9 than of N-3 on days 1 and 2 provided suggestive evidence for a second pathway for synthesis of the initial precursor of purine biosynthesis, phosphoribosylamine, perhaps utilizing ammonia rather than the amide-N of glutamine as nitrogen donor. In this limited study, the activity of this potential second pathway did not appear to be selectively increased in gout.
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PMID:The kinetics of intramolecular distribution of 15N in uric acid after administration of (15N) glycine. A reappraisal of the significance of preferential labeling of N-(3+9) of uric acid in primary gout. 435 99

Molybdenum belongs to a group of essential microelements and occurs in all components of the environment. Major Mo sources for man are foods, especially vegetable, to a lesser extent drinking water. Its metabolism is primarily influenced by interaction with other metals, specifically copper and iron. In the organism it is primarily accumulated in the liver, kidneys, skin and hard tissues. In the blood it binds specifically with alpha-2-macroglobulin, in the erythrocytic membrane with spectrin; it enhances the osmotic resistance of red blood cells. From the organism it is eliminated in the urine, bile and feces. The biochemical importance of molybdenum lies in that it catalyzes the oxidation of xanthine and purine bases and the reduction of nitrates and molecular nitrogen; it is also present in the prosthetic group of flavoprotein enzymes. As shown in both epidemiological and animal studies, molybdenum ions may prevent dental caries. Long-term overexposure to Mo may produce molybdenosis (teart) in cattle. Increased exposures of humans may be primarily encountered in the foundry industry, but the toxic manifestations are invariably nonspecific, similarly as in the case of other heavy metals. Molybdenum-exposed workers may also show elevated uric acid concentrations in their blood, simultaneously with clinical symptoms resembling gout (gout-like syndrome). A similar finding may also occur among individuals living in areas characterized by elevated molybdenum and decreased copper contents in soil. The maximum allowable concentration limits established for soluble and insoluble molybdenum compounds in the workplace air have been accepted in many countries, but their values vary in a wide range. No specific exposure test for molybdenum has been developed as yet.
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PMID:Effects of molybdenum on the organism (a review). 639 29

To determine whether patients with gout have a diet which is distinctive in quality or quantity a careful dietary questionnaire was posed over 7 days to 61 men with gout and 52 control subjects. The average daily intake of most nutrients, including total purine nitrogen, was similar except that the patients with gout drank significantly more alcohol. Beer was the most popular beverage, and 25 (41%) of those with gout consumed more than 60 g alcohol daily (equivalent to 2 . 5 litres of beer). The heavy drinkers had a significantly higher intake of purine nitrogen, half of which was derived from beer. Though the effect of ingested purine on the blood uric acid is difficult to estimate, it probably was sufficient to have a clinical effect, augmenting the hyperuricaemic effect of alcohol itself.
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PMID:A controlled study of diet in patients with gout. 684 59

Urate deposits within microtophi were found in 8% of unselected autopsies in Brisbane, Australia. Significant association were demonstrated with (a) a history of gouty arthritis and (b) the existence of nitrogen retention and renal disease of apparently primary, but not gouty, origin. However, in 26% of the patients, a retrospective survey of their medical records did not reveal any causative factor. The possible aetiological importance of the urine flow rate is stressed. The presence of medullary urate deposits at autopsy was most frequently associated with a history of gout or the presence of pre-existing and non-gouty renal disease, although no aetiological factor could be determined in a quarter of the cases.
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PMID:Urate deposits in the renal medulla. Prevalence and associations. 732 50

Findings on the efficacy of nutritional supplements used by athletes are reviewed. Many athletes have turned away from anabolic steroids and toward nutritional supplements in the hope of gaining a competitive edge without threatening their health. Athletes may require slightly more protein than sedentary people do to maintain positive nitrogen balance, but it is dubious whether extra dietary protein will help someone to achieve athletic goals. Purified amino acids have become a popular if expensive form of protein supplementation; there is no scientific evidence, however, to support their use. Excessive protein supplementation can lead to dehydration, gout, liver and kidney damage, calcium loss, and gastrointestinal effects. Supplementation with vitamins and minerals in excess of recommended daily allowances appears to have no effect on muscle mass or athletic performance. Other substances touted as having ergogenic properties are carnitine, cobamamide, growth hormone releasers, octacosanol, and ginseng; again, there is no reliable scientific evidence to support claims that products containing these compounds have ergogenic potential, and heavy supplementation may lead to adverse effects. Nutritional supplements are promoted through unsubstantiated claims by magazine advertisements, health food stores, coaches, and other sources. The FDA considers nutritional supplements to be foodstuffs, not drugs, and therefore has not required that they be proved safe and effective. Dosage guidelines are inadequate, and quality control is poor. The FDA has begun to revise regulations governing labeling and health claims for these products. There is little if any evidence that nutritional supplements have ergogenic effects in athletes consuming a balanced diet, and some products have the potential for harm.
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PMID:Efficacy of nutritional supplements used by athletes. 813 7

A case is described in which, after administration of diclofenac for 13 days for arthritis attributed to gout, the patient experienced erythema multiforme followed by muscle weakness, elevation of serum creatine phosphokinase (CPK) level from 101 to 83,770 U/L, 100% muscle isoenzyme, blood urea nitrogen (BUN) level from 15 to 87 mg/dL, creatinine level from 1.0 to 2.1 mg/dL and urine myoglobin level to 1,190 micrograms/dL (N < 1.2). The diagnosis was rhabdomyolysis due to diclofenac, with myoglobinuria resulting in mild renal failure. Treatment consisted of discontinuing diclofenac and administering sufficient fluids to prevent progression of myoglobinuric renal failure. Serum CPK level gradually returned to normal by day 50, BUN and creatinine levels by day 28, and muscle strength between day 90 and 180. Rhabdomyolysis due to diclofenac or to other nonsteroidal antiinflammatory drugs has not been reported.
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PMID:Case report: diclofenac-induced rhabdomyolysis. 870 74

A 59-year-old man with chronic obstructive pulmonary disease (COPD), atrial fibrillation, and gout developed acute dyspnea, cough, and diffuse muscle aches and pains. He had commenced colchicine (0.6 mg b.i.d. p.o.), for the first time, one month earlier for recurrent gout attacks. Clinical examination revealed atrial fibrillation, an exacerbation of his pulmonary disease, tender muscles, especially calves, and diffuse muscle weakness. Laboratory results included creatinine phosphokinase 6961 U/l (1% MB), microscopic hematuria, myoglobinuria, elevated creatinine 1.6 mg/dl, and blood urea nitrogen 17 mg/dl. COPD and atrial fibrillation were treated and colchicine was discontinued. The patient made a full recovery. This 2nd reported case of colchicine induced rhabdomyolysis is the first reported in the treatment of gout.
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PMID:Colchicine induced rhabdomyolysis. 933 Sep 53

Molybdenum does not exist naturally in the pure metallic form and of the 5 oxidation states (2-6) the predominant species are Mo(IV) and Mo(VI). Molybdenum rapidly polymerizes to a wide variety of complex polymolybdate compounds in solution. The vast majority of molybdenum is used in metallurgical applications (stainless steel, cast-iron alloys). Ammonium tetrathiomolybdate is an experimental chelating agent for Wilson's disease. For the general population, the diet is the most important source of molybdenum and concentrations in water and air usually are negligible. The average daily dietary intake is about 0.1-0.5 mg m.o. Molybdenum is an essential element with relatively low toxicity. Enzymes containing molybdenum catalyze basic metabolic reactions in the carbon, sulfur, and nitrogen cycles. Elimination of molybdenum occurs via the kidney and usually is complete within several weeks. Molybdenosis (teart) is a form of molybdenum toxicity that produces a disease in ruminants similar to copper-deficiency. Little data are available on the human toxicity of molybdenum. A gout-like syndrome and pneumoconiosis have been associated with excessive concentrations of molybdenum, but the inadequate design of the studies prevents an adequate determination of the etiology of these effects.
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PMID:Molybdenum. 1038 58

To determine the ability of cockatiels (Nymphicus hollandicus), a granivorous avian species, to adapt metabolically to high dietary protein levels, adult males (n = 26) were fed isocaloric diets containing 11, 20, 35 or 70% crude protein (CP) for 11 mo. Throughout the trial, body weight and breast muscle weight were maintained by 11, 20 or 70% CP. The 35% CP diet resulted in significantly greater body weight (P < 0.05) and whole-body lipid content (P < 0.05) compared with the 11% CP diet. The 20% CP diet resulted in greater breast muscle mass compared with 70% CP (P < 0.05). Activity of the amino acid catabolic enzymes alanine aminotransferase, aspartate aminotransferase and arginase as well as the gluconeogenic enzyme phosphoenolpyruvate carboxykinase were significantly increased with 70% CP (P < 0.05). Serum essential amino acids, urea and uric acid were also increased with 70% CP (P < 0.05), but the magnitude of their increase was similar to that found in omnivorous chickens fed a similar diet. There was no evidence of visceral gout, articular gout or renal pathology; however liver lesion severity, and specifically liver lipogranuloma severity, was significantly increased above 11% CP (P < 0.05). We conclude that cockatiels are able to up-regulate enzymes for amino acid catabolism as well as mechanisms for nitrogen excretion in response to high dietary protein levels, and that high dietary protein levels are not associated with kidney dysfunction in this avian species.
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PMID:Adult cockatiels (Nymphicus hollandicus) metabolically adapt to high protein diets. 1143 23

Xanthine dehydrogenase (XDH), a complex molybdo/iron-sulfur/flavoprotein, catalyzes the oxidation of hypoxanthine to xanthine followed by oxidation of xanthine to uric acid with concomitant reduction of NAD+. The 2.7 A resolution structure of Rhodobacter capsulatus XDH reveals that the bacterial and bovine XDH have highly similar folds despite differences in subunit composition. The NAD+ binding pocket of the bacterial XDH resembles that of the dehydrogenase form of the bovine enzyme rather than that of the oxidase form, which reduces O(2) instead of NAD+. The drug allopurinol is used to treat XDH-catalyzed uric acid build-up occurring in gout or during cancer chemotherapy. As a hypoxanthine analog, it is oxidized to alloxanthine, which cannot be further oxidized but acts as a tight binding inhibitor of XDH. The 3.0 A resolution structure of the XDH-alloxanthine complex shows direct coordination of alloxanthine to the molybdenum via a nitrogen atom. These results provide a starting point for the rational design of new XDH inhibitors.
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PMID:Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. 1179 16


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