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February 15, 1993Biochemical JournalOpen Access

Studies on the inhibitory mechanism of iodonium compounds with special reference to neutrophil NADPH oxidase

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Authors

VOValerie B. O’DonnellCardiff UniversityDTDavid G. TewGlaxoSmithKline (United Kingdom)OJOwen JonesAustralian National University

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Implication

Biochemical study reveals mechanism-based inhibition of neutrophil NADPH oxidase by diphenyleneiodonium, suggesting flavin cofactor adduct formation across flavoenzymes.

Key Points

  • To determine the biochemical mechanism through which diphenyleneiodonium inhibits neutrophil NADPH oxidase and establish whether reduced flavin cofactors serve as the activation site.
  • Measured time-dependent inhibition kinetics and turnover rates of NADPH oxidase in human and pig neutrophil membrane fractions exposed to diphenyleneiodonium.
  • Synthesized and characterized adducts between photoreduced flavins (FAD or FMN) and iodonium compounds using HPLC, absorbance spectroscopy, 1H-NMR, and fast-atom-bombardment mass spectrometry.
  • Diphenyleneiodonium inhibited human neutrophil membrane NADPH oxidase in a time- and turnover-dependent manner with a Ki of 5.6 μM, showing no inhibition without an activatory stimulus.
  • Isolated adducts between reduced flavins and iodonium inhibitors exhibited spectroscopic properties of substituted 4a,5-dihydroflavins, and intact recoverable flavin decreased markedly during turnover in pig membranes.

Cite This Study

O’Donnell et al. (1993) studied this question.

synapsesocial.com/papers/6a6f93df2163a0a01bc3db6chttps://doi.org/10.1042/bj2900041
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Inhibition of macrophage and endothelial cell nitric oxide synthase by diphenyleneiodonium and its analogs <sup>1</sup>1991 · 465 citations
  2. 2Oxygen-Dependent Microbial Killing by Phagocytes1978 · 2,492 citations
  3. 3Diphenylene iodonium as an inhibitor of the NADPH oxidase complex of bovine neutrophils1992 · 150 citations
  4. 4Mechanism of the superoxide-producing oxidase of neutrophils. O2 is necessary for the fast reduction of cytochrome b-245 by NADPH1985 · 127 citations
  5. 5Fluorescence and optical characteristics of reduced flavines and flavoproteins1974 · 385 citations