Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
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The nitrovasodilator, nicorandil, is a clinically effective antianginal agent. We tested whether nicorandil may also possess anti-free-radical characteristics, since the nicotinamide moiety of its molecular structure is a known hydroxyl radical scavenger. In vitro production of hydroxyl radicals by hypoxanthine plus xanthine oxidase in the presence of iron produced a marked degradation of deoxyribose. Nicorandil and the structural analogs, nicotinic acid and nicotinamide, produced significant inhibition of deoxyribose breakdown at concentrations equipotent to the classical hydroxyl radical scavenger, mannitol. Nicorandil also produced a concentration-dependent inhibition of superoxide anion production by canine neutrophils that were activated with either phorbol myristate acetate (PMA) or opsonized zymosan. This inhibition could not be mimicked by the analog, nicotinamide. While equimolar concentrations of nitroglycerin produced less inhibition of superoxide anion generation in opsonized zymosan-activated neutrophils than that observed with nicorandil, nitroglycerin did not alter free-radical production in PMA-stimulated neutrophils. Glyburide, the ATP-sensitive potassium-channel blocker, did not reverse the action of nicorandil on neutrophils. Thus, nicorandil is a uniquely different nitrovasodilator with anti-free-radical and neutrophil-modulating properties.
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PMID:Anti-free-radical and neutrophil-modulating properties of the nitrovasodilator, nicorandil. 132 63

Molybdenum, assayed by atomic absorption spectrometry, copurifies with the selenium-containing nicotinic acid hydroxylase from Clostridium barkeri. Fluorescence spectral studies on the enzyme indicate the presence, along with flavin, of another component. The fluorescence spectra of this component obtained after the aerobic denaturation of the nicotinic acid hydroxylase are similar to the fluorescence properties reported for the "pterin-like" cofactor from xanthine oxidase and several other molybdoproteins. Nicotinic acid hydroxylase from C. barkeri contains molybdenum, selenium, iron, acid-labile sulfur, and flavin with the occurrence of a "pterin-like" cofactor also a likely component.
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PMID:Occurrence of molybdenum in the nicotinic acid hydroxylase from Clostridium barkeri. 683 9

Serratia marcecens 2CC-1 utilizes quinaldic acid (quinoline 2-carboxylic acid) as sole source of carbon, nitrogen and energy. Growth of strain 2CC-1 on quinaldic acid as well as on nicotinic acid and hypoxanthine was inhibited completely by the molybdate antagonist tungstate, whereas growth on kynurenic acid and 6-hydroxynicotinic acid was not affected by tungstate. The synthesis of the molybdenum-containing hydroxylases quinaldic acid 4-oxidoreductase and nicotinic acid 6-oxidoreductase was found to be inducible. In addition, Serratia marcescens 2CC-1 produced a constitutively expressed xanthine oxidoreductase. Quinaldic acid 4-oxidoreductase was purified 1075-fold with a recovery of 5%. For catalytic activity, artificial electron acceptors were necessary. The 95-100-kDa enzyme was a heterodimer with subunit molecular masses of 75-80 kDa and 18-19 kDa. Quinaldic acid 4-oxidoreductase contained 2.3-3.7 g atom of iron and 0.5-0.6 g atom of molybdenum per mol of enzyme. The absorption spectrum exhibited maxima at 280 nm, 334 nm, 480 nm and a shoulder at 550 nm, with A280/A334 = 4.8, A280/A450 = 10.0, A280/A480 = 9.4, and A450/A550 = 1.6, suggesting the absence of a flavin cofactor. Acridine, quinacrine, ethylenediaminetetraacetate, 2,2'-dipyridyl, 1,10-phenanthroline and iodoacetate did not affect enzyme activity. p-Hydroxymercuribenzoate, m-arsenite, cyanide and methanol were effective inhibitors of quinaldic acid 4-oxidoreductase. Cyanide-inhibited enzyme was reactivated by treatment with S2-, indicating the presence of a pterin molybdenum cofactor with a monooxo-monosulfidotype molybdenum center. Quinaldic acid 4-oxidoreductase showed a very high substrate specificity, quinaldic acid being the only substrate found to be transformed significantly.
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PMID:Microbial metabolism of quinoline and related compounds. XVIII. Purification and some properties of the molybdenum- and iron-containing quinaldic acid 4-oxidoreductase from Serratia marcescens 2CC-1. 835 32