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)

Molybdenum toxicity and the interactions between copper, molybdenum and sulphate are reviewed. The main signs of molybdenum poisoning are poor growth and anaemia (rat, chick, rabbit, cattle and sheep), anorexia (rat), diarrhoea and achromotrichia (cattle and sheep), joint and bone deformities (rat, rabbit, cattle), central nervous system degeneration and loss of crimp in wool (sheep). The following topics are discussed: (1) The effect of sulphate and sulphur compounds on molybdenum toxicity. (2) The effect of molybdenum on tissue copper levels. (3) The effect of molybdenum on the distribution of copper in plasma. (4) The effect of molybdenum on uptake and excretion of copper. (5) The possible existence of copper(II) molybdate in vivo. (6) The influence of molybdenum on sulphide production by ruminal micro-organisms. (7) Competition between molybdenum and sulphate in intestinal transport. (8) Interaction of sulphur with copper in vivo. (9) The possible involvement of molybdenum in gout and multiple sclerosis in humans.
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PMID:Molybdenum toxicity: interactions between copper, molybdenum and sulphate. 100 22

Investigations into the reasons for the retarded growth and discolouration of a small area of a field of rape situated on the outskirts of Vienna revealed higher than normal levels of molybdenum in the soil (up to 430 micrograms/l) and in the water (up to 9.7 mg/l). The source of the pollution was traced to a neighbouring industrial plant that was emitting the metal via the chimney stack. A review of the literature on the toxic effects of molybdenum in general and as an air pollutant in particular is provided. This shows that, in contrast to animals, this effect is relatively small in humans and plants. Nevertheless, the occupation-related inhalation of the metal has been shown to be associated with pneumoconiosis and gout-like symptoms.
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PMID:[Molybdenum as an air pollutant]. 220 16

The results of simultaneous epidemiological surveys of the adult population (7000 persons) in the city of Tbilisi and workers at 7 enterprises of the machine-building and mining industries (9189) have shown that 0.29% of the population, mainly men aged over 40 with hereditary predisposition, obesity, carbohydrate metabolic derangement, consuming food rich in purine bases, national flavorings and spices, suffer from gout. A high prevalence of gout among workers of the mining industry and early age at the onset of disease suggest probable association of gout with some industrial factors (manganese, tungsten, molybdenum, bismuth).
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PMID:[Incidence and various risk factors for gout in the Georgian SSR]. 295 51

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

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

Gout affects mostly males over 40 years old and, occasionally, postmenopausal women. This pattern coincides with the pattern of iron accumulation. On the other hand, menstruating women are seldom afflicted by gout, because the monthly blood loss causes them to accumulate iron to a much lesser degree. Gout involves seven aspects: (1) uric acid overproduction from increased purines in the diet; (2) uric acid overproduction from ATP degradation; (3) uric acid overproduction from increased de novo synthesis of purines; (4) uric acid overproduction from increased DNA breakdown from cell damage; (5) decreased uric acid elimination, caused by molybdenum and sulfur binding to copper in the kidneys; (6) precipitation of sodium urate-iron crystals in the joints due to high ferritin and saturated transferrin and low CuZn-SOD and Cu-thionein in the joint; (7) development of inflammation, triggered by tyrosine bonding to the sodium-urate-iron crystals and being transformed by tyrosine kinase. Alcohol and iron greatly affect most of these aspects. Therefore, phlebotomy is suggested as therapy for gout patients, in order to eliminate the accumulated Fe. Furthermore, yearly blood donation is recommended for males with a family history of gout, so as to prevent Fe accumulation and avoid gout.
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PMID:Effect of gradual accumulation of iron, molybdenum and sulfur, slow depletion of zinc and copper, ethanol or fructose ingestion and phlebotomy in gout. 1061 42

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

Xanthine oxidase (XO) is a highly versatile flavoprotein enzyme, ubiquitous among species (from bacteria to human) and within the various tissues of mammals. The enzyme catalyses the oxidative hydroxylation of purine substrates at the molybdenum centre (the reductive half-reaction) and subsequent reduction of O(2) at the flavin centre with generation of reactive oxygen species (ROS), either superoxide anion radical or hydrogen peroxide (the oxidative half-reaction). Many diseases, or at least symptoms of diseases, arise from a deficiency or excess of a specific metabolite in the body. For an example of an excess of a particular metabolite that produces a disease state is the excess of uric acid which can led to gout. Inhibition of XO decreases the uric acid levels, and results in an antihyperuricemic effect. Allopurinol, first synthesised as a potential anticancer agent, is nowadays a clinically useful xanthine oxidase inhibitor used in the treatment of gout. There is overwhelming acceptance that xanthine oxidase serum levels are significantly increased in various pathological states like hepatitis, inflammation, ischemia-reperfusion, carcinogenesis and aging and that ROS generated in the enzymatic process are involved in oxidative damage. Thus, it may be possible that the inhibition of this enzymatic pathway would be beneficial. In this review the State of the Art will be presented, which includes a summary of the progress made over the past years in the knowledge of the structure and mechanism of the enzyme, associated pathological states, and in the efforts made towards the development of new xanthine oxidase inhibitors.
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PMID:Progress towards the discovery of xanthine oxidase inhibitors. 1186 Mar 55

Inhibitors of xanthine oxidoreductase block conversion of xanthine to uric acid and are therefore potentially useful for treatment of hyperuricemia or gout. We determined the crystal structure of reduced bovine milk xanthine oxidoreductase complexed with oxipurinol at 2.0 A resolution. Clear electron density was observed between the N2 nitrogen of oxipurinol and the molybdenum atom of the molybdopterin cofactor, indicating that oxipurinol coordinated directly to molybdenum. Oxipurinol forms hydrogen bonds with glutamate 802, arginine 880, and glutamate 1261, which have previously been shown to be essential for the enzyme reaction. We discuss possible differences in the hypouricemic effect of inhibitors, including allopurinol and newly developed inhibitors, based on their mode of binding in the crystal structures.
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PMID:Mechanism of inhibition of xanthine oxidoreductase by allopurinol: crystal structure of reduced bovine milk xanthine oxidoreductase bound with oxipurinol. 1860 May 58

An elevated level of blood uric acid (hyperuricemia) is the underlying cause of gout. Xanthine oxidase is the key enzyme that catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. Allopurinol, a widely used xanthine oxidase inhibitor is the most commonly used drug to treat gout. However, a small but significant portion of the population suffers from adverse effects of allopurinol that includes gastrointestinal upset, skin rashes and hypersensitivity reactions. Moreover, an elevated level of uric acid is considered as an independent risk factor for cardiovascular diseases. Therefore use of allopurinol-like drugs with minimum side effects is the ideal drug of choice against gout. In this study, we report the synthesis of a series of pyrimidin-5-one analogues as effective and a new class of xanthine oxidase inhibitors. All the synthesized pyrimidin-5-one analogues are characterized by spectroscopic techniques and elemental analysis. Four (6a, 6b, 6d and 6f) out of 20 synthesized molecules in this class showed good inhibition against three different sources of xanthine oxidase, which were more potent than allopurinol based on their respective IC(50) values. Molecular modeling and docking studies revealed that the molecule 6a has very good interactions with the Molybdenum-Oxygen-Sulfur (MOS) complex a key component in xanthine oxidase. These results highlight the identification of a new class of xanthine oxidase inhibitors that have potential to be more efficacious, than allopurinol, to treat gout and possibly against cardiovascular diseases.
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PMID:Synthesis and xanthine oxidase inhibitory activity of 7-methyl-2-(phenoxymethyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives. 2116 61


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