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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemistry common to molybdenum at the active centers of molybdoenzymes and at the surface of heterogeneous catalysts is described. Oxomolybdenum(VI) compounds catalyze selective oxidation of unsaturated hydrocarbons, e.g., propene to acrolein. Similarly, oxomolybdenum species take part in reactions catalyzed by molybdoenzymes, e.g., xanthine oxidase, sulfite oxidase, nitrate reductase. In these reactions H+, O2- or HO-, and electrons transfer between substrate molecules and molybdenum atoms and groups at the active centres. The chemistry involved is the acid-base and redox chemistry of molybdenum. Molybdenum disulfide catalyzes hydrogenation of unsaturated hydrocarbons, e.g., acetylene. The active site is a coordinately unsaturated molybdenum atom in a sulfur-ligand environment. The enzyme nitrogenase, which is a protein-bound iron-molybdenum sulfide, is also an excellent hydrogenation catalyst. Both catalysts exploit the chemistry of lower-valent molybdenum coordinated by sulfur. The extent to which understanding of the catalysis can be transferred between the two types of catalyst is assessed.
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PMID:Molybdenum in enzymatic and heterogeneous catalysis. 380 88

Two hereditary disorders of sulfur amino acid metabolism, beta-mercaptolactate-cysteine disulfideuria and sulfite oxidase deficiency, were described twenty years ago. Other examples of these disorders have been limited to about 5 of each in the world literature since then. Reasons for the apparent rarity of these conditions are discussed and the analytical procedures to identify them are reviewed. The detection of the first depends on the positive result of a cyanide-nitroprusside test followed by positive identification of the specific mixed disulfide. The enzyme mercaptopyruvate sulfur transferase has been shown to be deficient. In the second disorder of sulfite oxidase deficiency, the clinical presentation with progressive dystonia and dislocated lenses in an infant should suggest further laboratory investigations for this disorder which would not be detected by conventional laboratory screening procedures. Laboratory diagnosis can be obtained by use of the Merckoquant sulfite test on a fresh urine sample. Quantitative thiosulfate and taurine measurements can also be made. Positive identification of the specific amino acid S-sulfo-L-cysteine should also be made. The enzyme sulfite oxidase is missing from such organs as liver, kidney and brain. This latter condition may also be associated with xanthinuria. For this combined disorder of sulfite oxidase and xanthine oxidase, a deficiency of a molybdenum-containing cofactor has been demonstrated.
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PMID:A review of the clinical presentation and laboratory findings in two uncommon hereditary disorders of sulfur amino acid metabolism, beta-mercaptolactate cysteine disulfideuria and sulfite oxidase deficiency. 388 41

The reactions catalyzed by Mo enzymes each find the product differing from the substrate by two electrons and two protons (or some multiple thereof). The coordination chemistry of Mo suggests that there is a distinct relationship between acid-base and redox properties of Mo complexes, and that a coupled electron-proton transfer (to or from substrate) may be mediated by Mo in enzymes. Each of the Mo enzymes (nitrogenase, nitrate reductase, xanthine oxidase, aldehyde oxidase, and sulfite oxidase) is discussed; it is shown that a simple molecular mechanism embodying coupled proton-electron transfer can explain many key experimental observations. In view of this mechanism, the reasons for the use of Mo (from an evolutionary and chemical point of view) are discussed and other metals that may replace Mo are considered.
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PMID:Proposed molecular mechanism for the action of molybedenum in enzymes: coupled proton and electron transfer. 451 30

The administration of tungsten to rats maintained on a low molybdenum diet resulted in a dose- and time-dependent loss of sulfite oxidase (EC 1.8.3.1) and xanthine oxidase (EC 1.2.3.2) activities and hepatic molybdenum. These tungsten-treated animals appeared healthy, but were more susceptible to bisulfite toxicity. The median lethal dose for intraperitoneal bisulfite was found to be 181 mg of NaHSO(3) per kg for the animals deficient in sulfite oxidase, compared to 473 mg/kg for normal rats. The survival time of rats exposed to SO(2) at concentrations of 590 ppm and higher was seen to be inversely related to the level of SO(2). At 590 ppm and 925 ppm, control animals displayed symptoms of severe respiratory toxicity before death. At 2350 ppm of SO(2), death was preceded by seizures and prostration, symptoms observed with the systemic toxicity of injected bisulfite. At 590 ppm, animals deficient in sulfite oxidase were indistinguishable from control animals. However, at 925 ppm and 2350 ppm, the deficient animals displayed symptoms of systemic toxicity and had much shorter survival times. It is concluded that sulfite oxidase is instrumental in counteracting the toxic systemic effects of bisulfite, either injected or derived from respired SO(2). Respiratory death probably results from the toxicity of gaseous SO(2) before absorption as bisulfite and cannot be alleviated by sulfite oxidase. Sulfite oxidase does not appear to be inducible by either bisulfite or SO(2).
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PMID:Molecular basis of the biological function of molybdenum: the relationship between sulfite oxidase and the acute toxicity of bisulfite and SO2. 451 54

The reduced forms of xanthine oxidase, xanthine dehydrogenase, aldehyde oxidase, and sulfite oxidase are inactivated by cyanide. Following gel filtration to remove excess of reductant and cyanide, the isolated enzymes remain inactive. Thiocyanate, a product of inactivation of the oxidized forms of the xanthine- and aldehyde-oxidizing enzymes by cyanide, is not released during inactivation of the reduced enzymes. Studies with [14C]cyanide show that, while stoichiometric binding is required for the onset of inactivation, its continued binding is not essential to maintenance of the inactivated state. Electron paramagnetic resonance and absorption spectroscopic studies on the isolated inactivated enzymes show that prosthetic groups other than molybdenum are fully oxidized but that the molybdenum centers are modified. Reactivation is accomplished by incubation with suitable oxidants. Aerobic reactivation of inactive sulfite oxidase required only 1 eq of ferricyanide/active site. However, under rigorously anaerobic conditions, 3 to 4 mol of ferricyanide/active site were reduced, indicating that the molybdenum centers in the inactive enzyme had been reduced below the levels attained by the native enzyme during catalysis.
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PMID:Mechanisms of inactivation of molybdoenzymes by cyanide. 624 90

The effect of using [17O]water (24-50% enriched) as solvent on the Mo(V) electron paramagnetic resonance spectra of different reduced forms of xanthine oxidase has been investigated. All the Mo(V) signals are affected. Procedures are described, based on the use of difference spectral techniques, that facilitate interpretation of such spectra. The number of coupled oxygen atoms may be determined by estimation of the fraction of the spectrum that remains unchanged by the isotope at a known enrichment. For a species having two coupled oxygen atoms, the use of two different isotope enrichments permits elimination from the difference spectra of the contribution of the two singly substituted species. From the application of these methods, it is concluded that not only the strength of the hyperfine coupling of oxygen ligands of molybdenum but also their number and their exchangeability with the solvent vary from one reduced form of the enzyme to another. The inhibited species from active xanthine oxidase has been studied in the most detail. It has two weakly coupled oxygen atoms [A(17O)av = 0.1-0.2 mT] that do not exchange with the solvent. A cyclic structure is proposed for this species in which two oxygen ligands of molybdenum are bonded to the carbon of the formaldehyde or other alcohol or aldehyde molecule that reacted in producing the signal. Structures of the other signal-giving species from active xanthine oxidase (Very Rapid and Rapid types 1 and 2) are discussed, as is corresponding information on species from the desulfo enzyme and from sulfite oxidase.
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PMID:Numbers and exchangeability with water of oxygen-17 atoms coupled to molybdenum (V) in different reduced forms of xanthine oxidase. 629 49

The carbon monoxide oxidases (COXs) purified from the carboxydotrophic bacteria Pseudomonas carboxydohydrogena and Pseudomonas carboxydoflava were found to be molybdenum hydroxylases, identical in cofactor composition and spectral properties to the recently characterized enzyme from Pseudomonas carboxydovorans (O. Meyer, J. Biol. Chem. 257:1333-1341, 1982). All three enzymes exhibited a cofactor composition of two flavin adenine dinucleotides, two molybdenums, eight irons and eight labile sulfides per dimeric molecule, typical for molybdenum-containing iron-sulfur flavoproteins. The millimolar extinction coefficient of the COXs at 450 nm was 72 (per two flavin adenine dinucleotides), a value similar to that of milk xanthine oxidase and chicken liver xanthine dehydrogenase at 450 nm. That molybdopterin, the novel prosthetic group of the molybdenum cofactor of a variety of molybdoenzymes (J. Johnson and K. V. Rajagopalan, Proc. Natl. Acad. Sci. U.S.A. 79:6856-6860, 1982) is also a constituent of COXs from carboxydotrophic bacteria is indicated by the formation of identical fluorescent cofactor derivatives, by complementation of the nitrate reductase activity in extracts of Neurospora crassa nit-l, and by the presence of organic phosphate additional to flavin adenine dinucleotides. Molybdopterin is tightly but noncovalently bound to the protein. COX, sulfite oxidase, xanthine oxidase, and xanthine dehydrogenase each contains 2 mol of molybdopterin per mol of enzyme. The presence of a trichloroacetic acid-releasable, so-far-unidentified, phosphorous-containing moiety in COX is suggested by the results of phosphate analysis.
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PMID:Molybdopterin in carbon monoxide oxidase from carboxydotrophic bacteria. 658 59

A 4-year-old patient is described with hyperphenylalaninemia, severe retardation in development, severe muscular hypotonia of the trunk and hypertonia of the extremities, convulsions, and frequent episodes of hyperthermia without infections. Urinary excretion of neopterin, biopterin, pterin, isoxanthopterin, dopamine, and serotonin was very low, although the relative proportions of pterins were normal. In lumbar cerebrospinal fluid, homovanillic acid, 5-hydroxyindoleacetic acid, neopterin and biopterin were low. Oral administration of L-erythro tetrahydrobiopterin normalized the elevated serum phenylalanine within 4 h, serum tyrosine was increased briefly and serum alanine and glutamic acid for a longer time. Urinary dopamine and serotonin excretion were also increased. Administration of an equivalent dose of D-erythro tetrahydroneopterin was ineffective and demonstrated that this compound is not a cofactor in vivo and cannot be transformed into an active cofactor. GTP cyclohydrolase I activity was not detectable in liver biopsies from the patient. The presence of an endogenous inhibitor in the patient's liver was excluded. This is the first case of a new variant of hyperphenylalaninemia in which the formation of dihydroneopterin triphosphate and its pterin metabolites in liver is markedly diminished. Normal activities of xanthine oxidase and sulfite oxidase were apparent since uric acid levels were normal and no increase in hypoxanthine, xanthine, and S-sulfocysteine concentrations could be observed in urine. It is concluded that the molybdenum cofactor of these enzymes may not be derived from dihydroneopterin triphosphate in man. Also, since no gross abnormalities in the patient's immune system could be found, it seems unlikely that dihydroneopterin triphosphate metabolites, such as neopterin, participate actively in immunological processes, as postulated by others. See Note added in proof.
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PMID:GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia. 673 69

Molybdenum is found in most foods, with legumes, dairy products, and meats being the richest sources. This metal is considered essential because it is part of a complex called molybdenum cofactor that is required for the three mammalian enzymes xanthine oxidase (XO), aldehyde oxidase (AO), and sulfite oxidase (SO). XO participates in the metabolism of purines, AO catalyzes the conversion of aldehydes to acids, and SO is involved in the metabolism of sulfur-containing amino acids. Molybdenum deficiency is not found in free-living humans, but deficiency is reported in a patient receiving prolonged total parenteral nutrition with clinical signs characterized by tachycardia, headache, mental disturbances, and coma. The biochemical abnormalities in this acquired molybdenum deficiency include very low levels of uric acid in serum and urine (low XO activity) and low inorganic sulfate levels in urine (low SO activity). Inborn errors of isolated deficiencies of XO, SO, and molybdenum cofactor are described. Although XO deficiency is relatively benign, patients with isolated deficiencies of SO or molybdenum cofactor exhibit mental retardation, neurologic problems, and ocular lens dislocation. These abnormalities seem to be caused by the toxicity of sulfite and/or inadequate amounts of inorganic sulfate available for the formation of sulfated compounds present in the brain. XO and AO may also participate in the inactivation of some toxic substances, inasmuch as studies suggest that molybdenum deficiency is a factor in the higher incidence of esophageal cancer in populations consuming food grown in molybdenum-poor soil.
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PMID:Molybdenum: an essential trace element. 830 61

Xanthine dehydrogenase and sulfite oxidase from chicken liver are oxomolybdenum enzymes which catalyze the oxidation of xanthine to uric acid and sulfite to sulfate, respectively. Independent purification protocols have been previously described for both enzymes. Here we describe a procedure by which xanthine dehydrogenase and sulfite oxidase are purified simultaneously from the same batch of fresh chicken liver. Also, unlike the protocols described earlier, this procedure avoids the use of acetone extraction as well as a heat step, thus minimizing damage to the molybdenum centers of the enzymes.
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PMID:Purification of xanthine dehydrogenase and sulfite oxidase from chicken liver. 878 24


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