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Related Experiment Videos

Catalase-mediated nitric oxide formation from hydroxyurea.

Jinming Huang1, Daniel B Kim-Shapiro, S Bruce King

  • 1Departments of Chemistry and Physics, Wake Forest University, Winston Salem, NC 27109, USA.

Journal of Medicinal Chemistry
|June 25, 2004
PubMed
Summary

Hydroxyurea, a treatment for sickle cell disease, is converted to nitric oxide by catalase. This catalase-mediated pathway may explain how hydroxyurea therapy increases nitric oxide levels in patients.

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Hematology

Background:

  • Hydroxyurea is approved for treating sickle cell disease (SCD) and reduces painful crises.
  • Nitric oxide (NO) is a potential therapeutic agent for SCD.
  • Elevated NO metabolites are observed in patients treated with hydroxyurea, but the conversion mechanism is unclear.

Purpose of the Study:

  • To investigate the mechanism of in vivo conversion of hydroxyurea to nitric oxide.
  • To identify the role of catalase in hydroxyurea's NO-generating pathway.

Main Methods:

  • Chemiluminescence detection to measure nitrite and nitrate formation.
  • Spectroscopic studies to analyze enzyme-substrate interactions.
  • Trapping studies to identify reaction intermediates.

Related Experiment Videos

  • Oxyhemoglobin assay and EPR spectroscopy to detect nitric oxide release.

    • Main Results:

    • Catalase catalyzes the formation of nitrite and nitrate from hydroxyurea.
    • A ferrous-NO catalase complex is formed during the reaction.
    • A nitroso species is identified as an intermediate.
    • Nitric oxide is released from the ferrous-NO catalase complex.

    Conclusions:

    • A catalase-mediated pathway converts hydroxyurea to nitric oxide.
    • This pathway involves hydrogen peroxide-dependent oxidation and nitroxyl formation.
    • This mechanism provides insight into NO production during hydroxyurea therapy for SCD.