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Updated: Oct 21, 2026

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
08:57

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases

Published on: February 24, 2018

Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite

L A MacMillan-Crow1, J A Thompson

  • 1Departments of Surgery and Biochemistry/Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA. lmcrow@ccc.uab.edu

Archives of Biochemistry and Biophysics
|May 21, 1999
PubMed

Insights

Human manganese superoxide dismutase (MnSOD) inactivation by peroxynitrite (ONOO-) involves tyrosine oxidation and dityrosine formation, independent of specific active site tyrosine residues. This finding is crucial for understanding chronic inflammatory diseases.

Area of Science:

  • Biochemistry
  • Enzymology
  • Oxidative Stress

Background:

  • Human manganese superoxide dismutase (MnSOD) is a key antioxidant enzyme.
  • MnSOD is targeted by tyrosine nitration in chronic inflammatory diseases.
  • Peroxynitrite (ONOO-) inactivates MnSOD, nitrates tyrosine residues, and induces dityrosine formation.

Purpose of the Study:

  • To differentiate the roles of tyrosine nitration and oxidation in MnSOD inactivation by ONOO-.
  • To compare ONOO- treatment effects on wild-type MnSOD (WT-MnSOD) and a Y34F-MnSOD mutant.

Main Methods:

  • Treatment of WT-MnSOD and Y34F-MnSOD with ONOO-.
  • Assessment of MnSOD enzymatic inactivation.
  • Analysis of tyrosine nitration and dityrosine formation.

Main Results:

  • Both WT-MnSOD and Y34F-MnSOD showed similar sensitivity to ONOO--mediated inactivation.
  • Y34F-MnSOD exhibited reduced tyrosine nitration and increased dityrosine formation compared to WT-MnSOD.
  • Complete MnSOD inactivation by ONOO- can occur without nitration of the primary susceptible tyrosine residue.

Conclusions:

  • MnSOD inactivation by ONOO- is a complex process involving both tyrosine nitration and oxidation.
  • Tyrosine oxidation and dityrosine formation contribute to MnSOD inactivation.
  • These findings offer insights into MnSOD's role in chronic inflammation and disease pathogenesis.

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