The free amino acid tyrosine enhances the chlorinating activity of human myeloperoxidase

J Inorg Biochem. 2012 Jan;106(1):76-83. doi: 10.1016/j.jinorgbio.2011.09.018. Epub 2011 Sep 17.

Abstract

A key function of neutrophil myeloperoxidase (MPO) is the synthesis of hypochlorous acid (HOCl), a potent oxidizing agent that plays a cytotoxic role against invading bacteria and viruses at inflammatory sites and in phagosomes. MPO displayed a chlorinating activity preferably at acidic pH but at neutral pH MPO catalyzes mainly reactions of the peroxidase cycle. In the present work effects of tyrosine on the chlorinating activity of MPO were studied. At pH 7.4 we detected an increased HOCl production in the presence of tyrosine not only by the MPO-H(2)O(2)-Cl(-) system but also in suspensions of zymosan-activated neutrophils. An excess of H(2)O(2) is known to cause an accumulation of compound II of MPO blocking the generation of HOCl at neutral pH. As evidenced by spectral changes, tyrosine-induced activation of MPO to synthesize HOCl was due to the ability of tyrosine to reduce compound II back to the native state, thus accelerating the enzyme turnover. MPO-induced oxidation of tyrosine is relevant to what can be in vivo; we detected MPO-catalyzed formation of dityrosine in the presence of plasma under experimental conditions when tyrosine concentration was about three magnitudes of order less than the Cl(-) concentration. At acidic pH formation of compound II was impaired in the presence of chloride and dityrosine couldn't be detected in plasma. In conclusion, the ability of tyrosine to increase the chlorinating activity of MPO at neutral pH and enhanced values of H(2)O(2) may be very effective for the specific enhancement of HOCl production under acute inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Cells, Cultured
  • Halogenation / drug effects
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Hydrogen-Ion Concentration
  • Hypochlorous Acid / metabolism*
  • Microscopy, Fluorescence
  • Neutrophils / cytology
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Oxidants / pharmacology
  • Oxidation-Reduction
  • Peroxidase / metabolism*
  • Sulfhydryl Compounds / blood
  • Sulfhydryl Compounds / metabolism
  • Sulfhydryl Compounds / pharmacology
  • Taurine / analogs & derivatives
  • Taurine / metabolism
  • Tyrosine / metabolism
  • Tyrosine / pharmacology*

Substances

  • Antioxidants
  • Oxidants
  • Sulfhydryl Compounds
  • Taurine
  • Tyrosine
  • N-chlorotaurine
  • Hypochlorous Acid
  • Hydrogen Peroxide
  • Peroxidase