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MOLYBDENUM Rough file: 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. copper deficiency caused by molybdenum.docIn animals the terminal step in the pathway for degradation of sulphur-containing amino acids is the oxidation of sulphite to sulphate. This reaction is catalysed by the enzyme sulphite oxidase. The enzyme contains molybdenum and a cytochrome b5 type haem, is localized in the mitochondrial intermembrane space and transfers electrons from sulphite to cytochrome c on the inner membrane. The sulphite oxidase protein has a molecular weight of 110 000 (chicken) to 122 000 (human) and exists as a dimer of identical subunits. The haem and molybdenum cofactors are present on separate domains of the molecule. The structure of the molydbenum cofactor has not been worked out in detail, but this cofactor is known to be present in many other molybdoenzymes including xanthine oxidase and nitrate reductase. Three cases of genetic sulphite oxidase deficiency in humans have been reported. The three affected children displayed mental retardation, neurological abnormalities and dislocated ocular lenses. The biochemical basis for lack of enzyme activity in each case has been studied. All three have been shown to lack the sulphite oxidase protein, but in one case this appears to be secondary to a defect in synthesis of the molybdenum cofactor. Sulphite oxidase deficiency has been produced in the rat by administration of high levels of tungsten. Sulphite oxidase-deficient animals are particularly susceptible to the toxic effects of sulphite and atmospheric sulphur dioxide. molybdenum essential for oxidation of sulphite.docMechanisms for removal of copper (Cu) from metallothionein (MT) by tetrathiomolybdate (TTM) were examined in vivo and in vitro using the LEC rat, which accumulates Cu as MT owing to the hereditary disorder of this strain. In our previous experiment, repeated intraperitoneal injections of TTM were shown to remove approximately two-thirds of the Cu from the liver, and the Cu remaining in the liver changed from soluble MT-bound forms to nonsoluble unidentified forms. The present single intravenous injection of TTM changed only part of the distribution in the soluble fraction, and dimeric MT was assumed to be formed. The liver supernatant was treated in vitro with high and low doses of TTM. The former treatment removed all Cu bound to MT and the Cu distributed to high molecular weight proteins, while the latter treatment produced dimeric MT. The results indicate that Cu accumulated as MT can be removed differently by TTM according to its relative dose both in vivo and in vitro. Excess TTM removes Cu completely from MT, leaving apothionein, while lesser TTM than Cu removes Cu incompletely, leaving MT with unoccupied sulfhydryl groups which coordinate with Cu intermolecularly to form dimeric and polymeric MT through the -S-Cu-S- bridge. molybdenum--TTM removal of copper from MT.docCopper (Cu) accumulating in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color) is bound to metallothionein (MT). Mechanisms for the removal of Cu by tetrathiomolybdate (TTM) were studied by the high performance liquid chromatography/inductively coupled plasma--mass spectrometry (HPLC/ICP-MS) method. MT containing Cu and cadmium (Cd) (Cu,Cd-MT) was reacted with TTM at a molar ratio of TTM/Cu = 0.5. A complex containing Cu, Cd and molybdenum (Mo) was formed and migrated to a position corresponding to an MT dimer on a gel filtration column. This complex designated previously as a dimer of MT through -S-Cu-S- bridge was revised to be a complex formed between MT and TTM through (MT)-S-Cu-S-(TTM) bridge with differing numbers of TTM bound to MT molybdenum-copper-cadmium-MT complex.docTetrathiomolybdate (TTM) removes copper (Cu) accumulating in a form bound to metallothionein (MT) in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color). The first step in the removal of Cu from Cu-MT has been shown to form a complex between MT and TTM through (MT)-S-Cu-S-(TTM) bridges (referred to as MT/TTM complex). Additional TTM was demonstrated to remove Cu from MT/TTM complex as the second step to form Cu/TTM complex by liberating MT. The Cu/TTM complex binds specifically to albumin in serum and to high molecular weight proteins in the absence of albumin, and is assumed to be a form of Cu for efflux by the treatment with TTM. molybdenum removal of copper--two steps.docWilson's disease is an inherited disorder of copper accumulation. The basic defect is a failure of excretion of excess copper in the bile by the liver for loss in the stool. The accumulating copper causes damage primarily to the liver and the brain. Patients typically present in the second to the fourth decades of life with liver disease, a neurological disease of the movement disorder type, or a wide array of behavioural disturbances. Because the manifestations of Wilson's disease are so protean, and the disease masquerades so well as something else, recognition of the possibility of Wilson's disease is a major problem, leading to serious underdiagnosis of the disease. Excellent therapies exist for both the prophylaxis and treatment of Wilson's disease. The longer recognition and diagnosis are delayed, the greater the risk of permanent damage to liver and/or brain. The availability of effective therapy and the risks in delay or therapy make the earliest possible diagnosis critical. Once the disease comes under consideration, a series of diagnostic steps can be undertaken which almost always establish or rule out the diagnosis of Wilson's disease. These include urine copper, blood ceruloplasmin, slit lamp examination for Kayser-Fleischer rings, and liver biopsy with quantitative copper assay. Currently, there are 4 drugs being used as anticopper agents in Wilson's disease. These are zinc, which blocks intestinal absorption of copper, penicillamine and trientine, both of which are chelators that increase urinary excretion of copper, and tetrathiomolybdate which forms a tripartite complex with copper and protein, and can block copper absorption from the intestine, or render blood copper non-toxic. Zinc is clearly the treatment of choice, in our opinion, for maintenance therapy, for the treatment of the presymptomatic patient from the beginning and for the treatment of the pregnant patient, because of its complete efficacy and lack of toxicity. For the initial treatment of the patient presenting with mild liver failure, we empirically use a combination of trientine and zinc. Trientine gives a strong, fast, negative copper balance, and zinc induces hepatic metallothionein, which sequesters hepatic copper. For the initial treatment of patients presenting with neurological disease we use an experimental drug, tetrathiomolybdate, which provides rapid, safe control of copper. These latter patients are at great risk of serious permanent neurological worsening with penicillamine, and zinc is too slow-acting, in our judgment, to be optimal. molybdenum--TTM treatment of Wilson's--review.docAmmonium tetrathiomolybdate (TTM) is the treatment of choice for chronic Cu poisoning in sheep and is recommended in Wilson's disease. However, the long-term effects have not been fully evaluated and some evidence questions the long-term safety of the drug. The aim of the present study was to investigate the systemic distribution and retention of Cu and Mo in TTM-treated sheep of different breeds and Cu status. Low-Cu Cambridge sheep were divided into a TTM trial group (3.4 mg/kg, subcutaneously, on three alternate days per month, for 5 months) and a control group, and were killed at the end of the course or 7 months later. High-Cu sheep consisting of a Cu-supplemented (150 mg/kg) Cambridge group and a North Ronaldsay group were administered TTM as before and compared with untreated controls. Brain, liver, kidney, heart, skeletal muscle, pituitary, adrenals, tests and ovaries were retained for metal analysis. Mo accumulated in all organs including brain and pituitary (P < 0.02) in all TTM trial groups and was retained after cessation of treatment, except in liver, kidney and skeletal muscle. Cu was increased (P < 0.02) and retained in the cerebellum and medulla oblongata in the TTM-treated high-Cu Cambridge groups. Brain Cu v. Mo concentrations showed a strongly positive correlation (r. 0.7) in the high-Cu Ronaldsay group 7 months after TTM treatment. It is concluded that TTM is not all excreted but (Mo) is widely distributed and retained in many organs including brain and pituitary. In addition TTM may redistribute some displaced excess liver Cu (Cu-TTM) to the brain. The consequences of these disturbances await clarification. molybdenum--mo-cu accumulation in other organs.doc
From Dr. V: Mo is required for the xanthine oxidase enzyme for the breakdown of uric acid. you
get gout if you dont have normal xanthine oxididase. Mo is also for aldehyde
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