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 journalArticle

17 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalFree Radical Biology and Medicine
Volume10
Issue number1
DOIs
StatePublished - 1991

Fingerprint

Xanthine Oxidase
Hydroxyl Radical
Hydrogen Peroxide
Xanthine
Dimethyl Sulfoxide
Pentetic Acid
Chelating Agents
Formaldehyde
Superoxide Dismutase
Metals

Keywords

  • Autoinactivation
  • Flavin
  • Hydrogen peroxide
  • Hydroxyl radical
  • Xanthine oxidase

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Medicine(all)
  • Toxicology

Cite this

Inactivation of xanthine oxidase by hydrogen peroxide involves site-directed hydroxyl radical formation. / Terada, Lance S.; Leff, Jonathan A.; Guidot, David M.; Willingham, Irene R.; Repine, John E.

In: Free Radical Biology and Medicine, Vol. 10, No. 1, 1991, p. 61-68.

Research output: Contribution to journalArticle

Terada, Lance S. ; Leff, Jonathan A. ; Guidot, David M. ; Willingham, Irene R. ; Repine, John E. / Inactivation of xanthine oxidase by hydrogen peroxide involves site-directed hydroxyl radical formation. In: Free Radical Biology and Medicine. 1991 ; Vol. 10, No. 1. pp. 61-68.
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