کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1317854 976594 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The free amino acid tyrosine enhances the chlorinating activity of human myeloperoxidase
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
پیش نمایش صفحه اول مقاله
The free amino acid tyrosine enhances the chlorinating activity of human myeloperoxidase
چکیده انگلیسی

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-H2O2-Cl- system but also in suspensions of zymosan-activated neutrophils. An excess of H2O2 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 H2O2 may be very effective for the specific enhancement of HOCl production under acute inflammation.

At neutral pH tyrosine enhances the chlorinating activity of the heme protein myeloperoxidase (MPO). As evidenced by changes in absorption spectra, this effect is due to the ability of tyrosine to reduce MPO compound II to the ferric enzyme accelerating, thus, the turnover of the enzyme.Figure optionsDownload as PowerPoint slideHighlights
► Tyrosine enhances the chlorinating activity of myeloperoxidase (MPO) at neutral pH.
► An excess of H2O2 causes the accumulation of inactive compound II of MPO.
► Tyrosine reduces MPO compound II to the native state accelerating MPO cycling.
► Tyrosine-induced increase of HOCl generation was detected in neutrophils.
► Our results are relevant to the conditions realized at inflammatory site.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 106, Issue 1, January 2012, Pages 76–83
نویسندگان
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