Inactivation of xanthine oxidase by hydrogen peroxide involves site-directed hydroxyl radical formation

Lance S. Terada; Jonathan A. Leff; David M. Guidot; Irene R. Willingham; John E. Repine

doi:10.1016/0891-5849(91)90022-U

Inactivation of xanthine oxidase by hydrogen peroxide involves site-directed hydroxyl radical formation

Lance S. Terada, Jonathan A. Leff, David M. Guidot, Irene R. Willingham, John E. Repine

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

The mechanism of xanthine oxidase (XO) inactivation by hydrogen peroxide (H₂O₂) and its biologic significance are unclear. We found that the addition of increasing concentrations of H₂O₂ progressively decreased xanthine oxidase activity in the presence but not the absence of xanthine in vitro. Inactivatuion of XO by H₂O₂ was also enhanced by anaerobic reduction of XO by xanthine. Inactivation of XO by H₂O₂ was accompanied by prodcction of hydroxyl radical (·OH), measured as formation of formaldehyde from dimethylsulfoxide (DMSO). In contrast, addition of H₂O₂ to deflavo XO dit not produce ·OH. Inactivation of XO by H₂O₂ was decreased by simultaneous addition of the ·OH scavenger, DMSO. However, inactivation of XO by H₂O₂ and formation of ·OH were not decreased following addition of the metal chelator, DETAPAC, and/or the O₂ scavenger, superoxide dismutase. The results suggest that inactivation of XO by H₂O₂ occurs by production of ·OH following direct reduction of H₂O₂ by XO at the flavian site.

Original language	English (US)
Pages (from-to)	61-68
Number of pages	8
Journal	Free Radical Biology and Medicine
Volume	10
Issue number	1
DOIs	https://doi.org/10.1016/0891-5849(91)90022-U
State	Published - 1991

Keywords

Autoinactivation
Flavin
Hydrogen peroxide
Hydroxyl radical
Xanthine oxidase

ASJC Scopus subject areas

Biochemistry
Physiology (medical)

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10.1016/0891-5849(91)90022-U

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title = "Inactivation of xanthine oxidase by hydrogen peroxide involves site-directed hydroxyl radical formation",

abstract = "The mechanism of xanthine oxidase (XO) inactivation by hydrogen peroxide (H2O2) and its biologic significance are unclear. We found that the addition of increasing concentrations of H2O2 progressively decreased xanthine oxidase activity in the presence but not the absence of xanthine in vitro. Inactivatuion of XO by H2O2 was also enhanced by anaerobic reduction of XO by xanthine. Inactivation of XO by H2O2 was accompanied by prodcction of hydroxyl radical (·OH), measured as formation of formaldehyde from dimethylsulfoxide (DMSO). In contrast, addition of H2O2 to deflavo XO dit not produce ·OH. Inactivation of XO by H2O2 was decreased by simultaneous addition of the ·OH scavenger, DMSO. However, inactivation of XO by H2O2 and formation of ·OH were not decreased following addition of the metal chelator, DETAPAC, and/or the O2 scavenger, superoxide dismutase. The results suggest that inactivation of XO by H2O2 occurs by production of ·OH following direct reduction of H2O2 by XO at the flavian site.",

keywords = "Autoinactivation, Flavin, Hydrogen peroxide, Hydroxyl radical, Xanthine oxidase",

author = "Terada, {Lance S.} and Leff, {Jonathan A.} and Guidot, {David M.} and Willingham, {Irene R.} and Repine, {John E.}",

year = "1991",

doi = "10.1016/0891-5849(91)90022-U",

language = "English (US)",

volume = "10",

pages = "61--68",

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T1 - Inactivation of xanthine oxidase by hydrogen peroxide involves site-directed hydroxyl radical formation

AU - Terada, Lance S.

AU - Leff, Jonathan A.

AU - Guidot, David M.

AU - Willingham, Irene R.

AU - Repine, John E.

PY - 1991

Y1 - 1991

N2 - The mechanism of xanthine oxidase (XO) inactivation by hydrogen peroxide (H2O2) and its biologic significance are unclear. We found that the addition of increasing concentrations of H2O2 progressively decreased xanthine oxidase activity in the presence but not the absence of xanthine in vitro. Inactivatuion of XO by H2O2 was also enhanced by anaerobic reduction of XO by xanthine. Inactivation of XO by H2O2 was accompanied by prodcction of hydroxyl radical (·OH), measured as formation of formaldehyde from dimethylsulfoxide (DMSO). In contrast, addition of H2O2 to deflavo XO dit not produce ·OH. Inactivation of XO by H2O2 was decreased by simultaneous addition of the ·OH scavenger, DMSO. However, inactivation of XO by H2O2 and formation of ·OH were not decreased following addition of the metal chelator, DETAPAC, and/or the O2 scavenger, superoxide dismutase. The results suggest that inactivation of XO by H2O2 occurs by production of ·OH following direct reduction of H2O2 by XO at the flavian site.

AB - The mechanism of xanthine oxidase (XO) inactivation by hydrogen peroxide (H2O2) and its biologic significance are unclear. We found that the addition of increasing concentrations of H2O2 progressively decreased xanthine oxidase activity in the presence but not the absence of xanthine in vitro. Inactivatuion of XO by H2O2 was also enhanced by anaerobic reduction of XO by xanthine. Inactivation of XO by H2O2 was accompanied by prodcction of hydroxyl radical (·OH), measured as formation of formaldehyde from dimethylsulfoxide (DMSO). In contrast, addition of H2O2 to deflavo XO dit not produce ·OH. Inactivation of XO by H2O2 was decreased by simultaneous addition of the ·OH scavenger, DMSO. However, inactivation of XO by H2O2 and formation of ·OH were not decreased following addition of the metal chelator, DETAPAC, and/or the O2 scavenger, superoxide dismutase. The results suggest that inactivation of XO by H2O2 occurs by production of ·OH following direct reduction of H2O2 by XO at the flavian site.

KW - Autoinactivation

KW - Flavin

KW - Hydrogen peroxide

KW - Hydroxyl radical

KW - Xanthine oxidase

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Inactivation of xanthine oxidase by hydrogen peroxide involves site-directed hydroxyl radical formation

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Keywords

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