Aldehyde oxidase reduction

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). 

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. 

Kitamura S, Tatsumi K. Reduction of tertiary amine N-oxides by liver preparations function of aldehyde oxidase as a major N-oxide reductase. Biochem Biophys Res Commun 1984 121(3) 749-754. 

A major class of enzymes that catalyze oxidation-reduction reactions. This class includes dehydrogenases, reductases, oxygenases, peroxidases, and a few synthases. Examples include alcohol dehydrogenase (EC 1.1.1.1), aldehyde oxidase (EC 1.2.3.1), orotate reductase (EC 1.3.1.14), glutamate synthase (EC 1.4.1.14), NAD(P) transhydrogenase (EC 1.6.1.1), and glutathione peroxidase (EC 1.11.1.9). 

PHYSICAL ORGANIC CHEMISTRY NOMENCLATURE ALDEHYDE DEHYDROGENASE ALDEHYDE HYDRATION ALDEHYDE OXIDASE ALDEHYDE OXIDOREDUCTASE ALDOSE REDUCTASE Aldehyde reduction to alcohols, BOROHYDRIDE REDUCTION ALDOLASE Aldolase reduction,... 

Aldehydes and Ketones. Many metabolic routes are possible, including both oxidation and reduction. However, oxidations are more common. Aldehydes are very susceptible to oxidation, which is catalyzed by various enzymes including aldehyde oxidase and aldehyde dehydrogenase this oxidation yields a carboxylic acid. Ketones, on the other hand, tend to be stable to oxidation. Conversely, aldehydes are seldom metabolized by reduction. Ketones, however, frequently undergo reduction to a secondary alcohol this is particularly true for a,P-unsaturated ketones. 

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. 

The cofactors of both xanthine and aldehyde oxidases belong to the LMoVI(S)(0) subfamily (see Section IV). However, inactive dioxo forms, LMovi(0)2, of both xanthine and aldehyde oxidase are known. These dioxo forms do not catalyze oxidation of the respective substrates of these enzymes. The Mov/Molv redox potential for the inactive bis(oxido) form of xanthine oxidase differs from the oxido-sulfido form by -30 mV (bovine xanthine oxidase) and -lOOmV (chicken liver xanthine oxidase) [91]. Although the difference is small, given the xanthine/uric acid reduction potential (-360 mV), it is possible that the Mov/MoIV couple (-433 mV) of the chicken-liver xanthine oxidase bis(ox-ido) form impedes the effective oxidation of xanthine for redox reasons alone. However, the bis(oxido) form of bovine xanthine oxidase (with a reduction potential of -386 mV) should be able to oxidize xanthine, since the redox potential, and hence the thermodynamic driving force, is sufficient for activity [91,92,99]. As substrate oxidation does not occur, the chemical differences between the bis(oxido) and oxido-sulfido (Movl) forms must be critical to the dramatic difference in activity (see Section VI.E.l). 

Sugihara K, Kitamura S, Tatsumi K. Involvement of mammalian liver cytosols and aldehyde oxidase in reductive metabolism of zonisamide. Drug Metab Dispos 1996 24 199-202. 

Kitamura, S., and Tatsumi, K. Involvement of liver aldehyde oxidase in the reduction of nicotinamide N-oxide. Biochem Biophys Res Commun 120 692-703, 19846. 

In this section are described the important chemical features of those substrates which are oxidized by the molybdenum hydroxylases. Although these enzymes, particularly aldehyde oxidase, also catalyse numerous reductive reactions under anaerobic conditions in vitro, it has not yet been established whether they occur under physiological conditions and there are as yet insufficient examples of any one reduction reaction to permit any conclusions regarding the structure of substrates. Thus, such reactions will not be discussed here (see [11] and references therein). Properties of those inhibitors which bind at the Mo centre and are also substrate analogues will also be included. However, the interaction of inhibitors such as cyanide and arsenite with the molybdenum hydroxylases and the mechanism of action of the specific xanthine oxidase inhibitor, allo-purinol, have been comprehensively described elsewhere [8, 12, 14, 157]. 

Aldehyde oxidases (AO) are also molybdenum-containing enzymes that, like XO, exist as homodimers of 300 Kdaltons. It is presumed that they behave mechanistically similarly to XO. Both AO and XO can mediate reductive reactions through the transfer of electrons from FADH2 to oxidized xenobiotic. For example, zonisamide can be reduced by AO to 2-sulfamoylacetylphenol. 

Maheshwari, P. P.A. Murphy Z.L. Nikolov. Characterization and application of porcine liver aldehyde oxidase in the off-flavor reduction of soy proteins. /. Agric. Food Chem. 1997, 45, 2488-2495. 

For sulfoxides/sulfides, oxidation is catalyzed by cytochrome P-450 and flavin monooxygenases, whereas the reductive metabolism is catalyzed by aldehyde oxidase and/or thiotedocin-linked enzymes. The fiver as well as the gut and bacterial flora are potential sites for the formation of sulfide metabolites. 

Mammalian aldehyde oxidases (AOs) catalyze the oxidation of aldehydes to carboxylic acids and play important roles in the metabolism of N-heterocyclic compounds, the reduction of nitro-aromatic compounds and the... 

Enzymes catalysing reductions are also found in liver microsomes, e.g. azo-benzene reductase and nitroreductase. Oxidation reactions, which are not due to cytochrome P-450 are catalysed by hexahydrobenzoate dehydrogenase, alcohol dehydrogenase, aldehyde dehydrogenase, xanthine oxidase, and aldehyde oxidase. Several amines are oxidised by monoamine oxidase or diamine oxidase. 

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