Xanthine aldehyde oxidase

Molybdenum. Molybdenum is a component of the metaHoen2ymes xanthine oxidase, aldehyde oxidase, and sulfite oxidase in mammals (130). Two other molybdenum metaHoen2ymes present in nitrifying bacteria have been characteri2ed nitrogenase and nitrate reductase (131). The molybdenum in the oxidases, is involved in redox reactions. The heme iron in sulfite oxidase also is involved in electron transfer (132). 

Xanthine oxidase, mol wt ca 275,000, present in milk, Hver, and intestinal mucosa (131), is required in the cataboHsm of nucleotides. The free bases guanine and hypoxanthine from the nucleotides are converted to uric acid and xanthine in the intermediate. Xanthine oxidase cataly2es oxidation of hypoxanthine to xanthine and xanthine to uric acid. In these processes and in the oxidations cataly2ed by aldehyde oxidase, molecular oxygen is reduced to H2O2 (133). Xanthine oxidase is also involved in iron metaboHsm. Release of iron from ferritin requires reduction of Fe " to Fe " and reduced xanthine oxidase participates in this conversion (133). 

Of the mammalian enzymes, the sulphite oxidase of bovine liver has only recently been discovered to contain molybdenum (15). The better known molybdenum enzymes, xanthine oxidase from cows milk (31) and aldehyde oxidase from rabbit liver (16) are closely related to one another as they are to the xanthine dehydrogenases from chicken liver (17) and from bacteria (18). 

So little is known about molybdenum enzymes other than milk xanthine oxidase that there is little to be said by way of general conclusions. In all cases where there is direct evidence (except possibly for xanthine dehydrogenase from Micrococcus lactilyticus) it seems that molybdenum in the enzymes does have a redox function in catalysis. For the xanthine oxidases and dehydrogenases and for aldehyde oxidase, the metal is concerned in interaction of the enzymes with reducing substrates. However, for nitrate reductase it is apparently in interaction with the oxidizing substrate that the metal is involved. In nitrogenase the role of molybdenum is still quite uncertain. 

In addition to these more-or-less well characterized proteins, iron is known to be bound to certain flavoproteins such as succinic dehydrogenase (20), aldehyde oxidase (27), xanthine oxidase (22) and dihydrooro-tate dehydrogenase (23). Iron is present and functional in non-heme segments of the electron transport chain but again no real structural information is at hand (24). 

Saito et al. (134) found that the cytosolic nitroreductase activity was due to DT-diaphorase, aldehyde oxidase, xanthine oxidase plus other unidentified nitroreductases. As anticipated, the microsomal reduction of 1-nitropyrene was inhibited by 0 and stimulated by FMN which was attributed to this cofactor acting as an electron shuttle between NADPH-cytochrome P-450 reductase and cytochrome P-450. Carbon monoxide and type II cytochrome P-450 inhibitors decreased the rate of nitroreduction which was consistent with the involvement of cytochrome P-450. Induction of cytochromes P-450 increased rates of 1-aminopyrene formation and nitroreduction was demonstrated in a reconstituted cytochrome P-450 system, with isozyme P-448-IId catalyzing the reduction most efficiently. 

R is an electron-donor substrate such as purine or xanthine and A is an electron acceptor such as 02 or NAD+. It is thought that the in vivo mammalian form of xanthine oxidase uses NAD+ as acceptor and is therefore, more appropriately named xanthine dehydrogenase. No evidence exists for a dehydrogenase form of aldehyde oxidase. The specificities of xanthine oxidase and aldehyde oxidase have been extensively catalogued (96), and the mechanism and properties of these enzymes have been reviewed (97, 98). 

Panoutsopoulos GI, Beedham C. Kinetics and specificity of guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase towards substituted benzaldehydes. Acta Biochim Pol 2004 51(3) 649-663. 

Molybdenum Milk, milk products dried legumes or pulses liver and kidney grains Prosthetic group of enzymes aldehyde oxidase Xanthine oxidase Electron transfer chain enzymes... 

Methylation of some form of 6-mercaptopurine in man has been established by the identification of 6-(methylsulphinyl)-8-hydroxypurine (LXV), 6-(methylthio)uric acid (LX), and 6-(methylthio)-8-hydroxy-A -glucuronide (LXVll). The oxidation of 6-(methylthio)purine to 6-(methylthio)-8-hydroxy-purine (LXVl) is mediated much more rapidly by rabbit liver aldehyde oxidase than by xanthine oxidase, and the oxidation is not inhibited by 4-hydroxy-pyrazolo [3, 4-d] pyrimidine [269], which is known to be an effective inhibitor of xanthine oxidase, and consequently, of the oxidation of 6-mercaptopurine [12,268]. 

METHOD OF CONTINUOUS VARIATION MOLYBDENUM COFACTOR (MoCo) Molybdenum-dependent reactions, ALDEHYDE OXIDASE MOLYBDOPTERIN NITRATE REDUCTASE NITROGENASE SULFITE OXIDASE XANTHINE DEHYDROGENASE MOLYBDOPTERIN... 

The monooxygenase group of enzymes includes the non-P450 hydroxylases which catalyze the insertion of a hydroxyl group to replace a hydrogen atom at a saturated carbon [6-8] and the non-heme-dependent oxygenases such as the flavin-molybdenum-cobalt-dependent xanthine oxidase and aldehyde oxidase... 

An EPR signal, characteristic for the superoxide radical, was observed by the rapid-freezing technique in the oxidation at pH 10 of xanthine by dioxygen catalysed by xanthine oxidase (EC 1,2.3.2) The enzymatic reduction of dioxygen by aldehyde oxidase (EC 1.2.3.1) produces also the superoxide radical. 

Purine oxidation. The oxidation of purines and purine derivatives is catalyzed by xanthine oxidase. For example, the enzyme oxidizes hypoxanthine to xanthine and thence uric acid (Fig. 4.34). Xanthine oxidase also catalyzes the oxidation of foreign compounds, such as the nitrogen heterocycle phthalazine (Fig. 4.35). This compound is also a substrate for aldehyde oxidase, giving the same product. 

In addition to these classical aromatic ring hydroxylations, many nitrogen heterocycles are substrates for molybdenum-containing enzymes, such as xanthine oxidase and aldehyde oxidase, which are present in the hepatic cytosolic fractions from various animal species. The molybdenum hydroxylases (B-75MI10902) catalyze the oxidation of electron-deficient carbons in aromatic nitrogen heterocycles. The reactions catalyzed by these enzymes are generally represented by equations (2) and (3). 

Ho, C. Y. and Clifford, A. J. 1976. Digestion and absorption of bovine milk xanthine oxidase and its role as an aldehyde oxidase. J. Nutr. 106, 1600-1609. 

Coughlan, M. P. 1980. Aldehyde oxidase, xanthine oxidase and xanthine dehydrogenase. Hydroxylases containing molybdenum, iron-sulphur and flavin. In Molybdenum and Molybdenum-Containing Enzymes. M.P. Coughlan (Editor). Pergamon Press, Oxford, pp. 119-185. 

Fe prosthetic groups.282 283 A group of aldehyde oxidases and xanthine dehydrogenases also contain molybdenum as well as iron (Chapter 16). In every case the metal ions are bound independently of the flavin.2833... 

Long recognized as an essential element for the growth of plants, molybdenum has never been directly demonstrated as a necessary animal nutrient. Nevertheless, it is found in several enzymes of the human body, as well as in 30 or more additional enzymes of bacteria and plants.632 Aldehyde oxidases,633 xanthine oxidase of liver and the related xanthine dehydrogenase, catalyze the reactions of Eqs. 16-58 and 16-59 and contain molybdenum that is essential for catalytic activity. Xanthine oxidase also contains two Fe2S2 clusters and bound FAD. The enzymes can also... 

Xanthine oxidase, xanthine dehydrogenase and aldehyde oxidase 658... 

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