Studies on the specificity toward aldehyde substrates and steady-state kinetics of xanthine oxidase

Morpeth, F.F.

doi:10.1016/0167-4838(83)90207-8

Cited by 55 publications

(41 citation statements)

References 31 publications

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“…Aldehyde oxidase and xanthine oxidase also catalyze the oxidation of aldehydes to their corresponding carboxylic acid [7][8][9]. However, the relative importance of these enzymes, compared to that of aldehyde dehydrogenase, in the metabolism of these compounds has not been established.…”

Section: Discussionmentioning

confidence: 99%

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Metabolism of Isovanillin by Aldehyde Oxidase, Xanthine Oxidase, Aldehyde Dehydrogenase and Liver Slices

Panoutsopoulos

Beedham

2005

Pharmacology

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Aromatic aldehydes are good substrates of aldehyde dehydrogenase activity but are relatively poor substrates of aldehyde oxidase and xanthine oxidase. However, the oxidation of xenobiotic-derived aromatic aldehydes by the latter enzymes has not been studied to any great extent. The present investigation compares the relative contribution of aldehyde dehydrogenase, aldehyde oxidase and xanthine oxidase activities in the oxidation of isovanillin in separate preparations and also in freshly prepared and cryopreserved liver slices. The oxidation of isovanillin was also examined in the presence of specific inhibitors of each oxidizing enzyme. Minimal transformation of isovanillin to isovanillic acid was observed in partially purified aldehyde oxidase, which is thought to be due to residual xanthine oxidase activity. Isovanillin was rapidly metabolized to isovanillic acid by high amounts of purified xanthine oxidase, but only low amounts are present in guinea pig liver fraction. Thus the contribution of xanthine oxidase to isovanillin oxidation in guinea pig is very low. In contrast, isovanillin was rapidly catalyzed to isovanillic acid by guinea pig liver aldehyde dehydrogenase activity. The inhibitor studies revealed that isovanillin was predominantly metabolized by aldehyde dehydrogenase activity. The oxidation of xenobiotic-derived aromatic aldehydes with freshly prepared or cryopreserved liver slices has not been previously reported. In freshly prepared liver slices, isovanillin was rapidly converted to isovanillic acid, whereas the conversion was very slow in cryopreserved liver slices due to low aldehyde dehydrogenase activity. The formation of isovanillic acid was not altered by allopurinol, but considerably inhibited by disulfiram. It is therefore concluded that isovanillin is predominantly metabolized by aldehyde dehydrogenase activity, with minimal contribution from either aldehyde oxidase or xanthine oxidase.

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Section: Discussionmentioning

confidence: 99%

“…The molybdenum hydroxylases, aldehyde oxidase and xanthine oxidase, oxidize a wide range of substrates, including aldehydes [7][8][9] and N-heterocycles [10][11][12]. However, the contribution of these enzymes to the metabolism of aldehydes has largely been ignored.…”

Section: Introductionmentioning

confidence: 99%

Metabolism of Isovanillin by Aldehyde Oxidase, Xanthine Oxidase, Aldehyde Dehydrogenase and Liver Slices

Panoutsopoulos

Beedham

2005

Pharmacology

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“…4). Binding of substrate in the outer compartment (IPP1 site) may explain substrate inhibition observed for Mop (12) and xanthine oxidase (40,45) when release of product through the "swinging doors" formed by Leu-394, Phe-425, Phe-494, Leu-497, and Leu-626, which separate inner and outer compartments, are blocked by waiting substrate molecules. We also suggest the outer, very spacious compartment as the binding site of voluminous inhibitors of xanthine oxidase (46).…”

Section: Discussionmentioning

confidence: 99%

A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes.

Huber

Hof

Duarte

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

240

284

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“…All tested XO substrates, acetaldehyde, xanthine, and hypoxanthine, provided qualitatively similar results in regard to the bicarbonate-dependent oxidation of DHR to rhodamine (Figs. [3][4][5] and of DMPO to the DMPO/ ⅐ OH radical adduct (Figs. 6 -8).…”

Section: Production Of Carbonate Radical Anion Monitored By Spin Trapmentioning

confidence: 99%

Production of the Carbonate Radical Anion during Xanthine Oxidase Turnover in the Presence of Bicarbonate

Bonini¹,

Miyamoto²,

Mascio

et al. 2004

Journal of Biological Chemistry

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Xanthine oxidase is generally recognized as a key enzyme in purine catabolism, but its structural complexity, low substrate specificity, and specialized tissue distribution suggest other functions that remain to be fully identified. The potential of xanthine oxidase to generate superoxide radical anion, hydrogen peroxide, and peroxynitrite has been extensively explored in pathophysiological contexts. Here we demonstrate that xanthine oxidase turnover at physiological pH produces a strong one-electron oxidant, the carbonate radical anion. The radical was shown to be produced from acetaldehyde oxidation by xanthine oxidase in the presence of catalase and bicarbonate on the basis of several lines of evidence such as oxidation of both dihydrorhodamine 123 and 5,5-dimethyl-1-pyrroline-N-oxide and chemiluminescence and isotope labeling/mass spectrometry studies. In the case of xanthine oxidase acting upon xanthine and hypoxanthine as substrates, carbonate radical anion production was also evidenced by the oxidation of 5,5-dimethyl-1-pyrroline-N-oxide and of dihydrorhodamine 123 in the presence of uricase. The results indicated that Fenton chemistry occurring in the bulk solution is not necessary for carbonate radical anion production. Under the conditions employed, the radical was likely to be produced at the enzyme active site by reduction of a peroxymonocarbonate intermediate whose formation and reduction is facilitated by the many xanthine oxidase redox centers. In addition to indicating that the carbonate radical anion may be an important mediator of the pathophysiological effects of xanthine oxidase, the results emphasize the potential of the bicarbonate-carbon dioxide pair as a source of biological oxidants.

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Studies on the specificity toward aldehyde substrates and steady-state kinetics of xanthine oxidase

Cited by 55 publications

References 31 publications

Metabolism of Isovanillin by Aldehyde Oxidase, Xanthine Oxidase, Aldehyde Dehydrogenase and Liver Slices

Metabolism of Isovanillin by Aldehyde Oxidase, Xanthine Oxidase, Aldehyde Dehydrogenase and Liver Slices

A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes.

Production of the Carbonate Radical Anion during Xanthine Oxidase Turnover in the Presence of Bicarbonate

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