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

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.

• Authors: Irina I Vlasova, Alexey V Sokolov, Juergen Arnhold
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 106 Issue 1 Pg. 76-83 (Jan 2012) ISSN: 1873-3344 [Electronic] United States
• PMID: 22112843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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