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975858 
Journal Article 
Abstract 
Peroxiredoxin 2 as a peroxynitrite reductase in the erythrocyte 
Hugo, M; Manta, B; Trujillo, M; Ferrer-Sueta, G; Denicola, A 
2008 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
45 
Suppl. 
S70-S70 
English 
WOS:000260867900194 
is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts
Peroxiredoxins (PRDXs) are a large family of antioxidant enzymes which reduce hydroperoxides at the expense of thioredoxin (Trx) or other electron donors. Peroxiredoxin 2 (PRDX2) is a typical 2-Cys peroxiredoxin, and is the third most abundant protein in the erythrocyte. the catalytic cycle involves the reaction of the oxidizing substrate with the peroxidatic cysteine of one subunit (C52-SH) to yield a cysteine sulfenic acid (C52-SOH), which then reacts with the resolving cysteine (C170- SH) of other subunit to form an intermolecular disulfide bond. Trx reduces this disulfide bond to regenerate active PRDX2 initiating a new catalytic cycle. Overoxidation of the peroxidatic cysteine to sulfinic acid (C52-SO2H) has been observed under turnover with relatively low concentrations of H2O2, yielding an inactive peroxidase. the erythrocyte is a cell particularly exposed to oxidative stress, mainly due to autoxidation of hemoglobin (5 mM), but also functions as a sink for plasma reactive oxygen and nitrogen species. We studied the reactivity of human erythrocyte PRDX2 with H2O2 and peroxynitrite by competition kinetics. the enzyme is extremely efficient in reducing H2O2 (k2 = 2 x 108 M-1 s-1, pH 7.4 and 25ºC). In addition, reduces peroxynitrite to nitrite with a k2 = 1 x 107 M-1 s-1 (pH 7.4, 25ºC), one of the highest reported rate constants for peroxynitrite reduction. Overoxidation of the enzyme was observed under excess of oxidant (H2O2 as well as peroxynitrite). a closer look on the mechanism of peroxyntirite-mediated over-oxidation showed not only a direct reaction of peroxynitrite with cysteine sulfenic acid, but also participation of peroxynitrite-derived radicals. Our results point to PRDX2 as the preferential target for peroxynitrite reaching the inside of the red blood cell and positions this peroxirredoxin as a key antioxidant enzyme of the erythrocyte. 
Society for Free Radical Biology and Medicine 15th Annual Meeting 
Indianapolis, IN 
November 19-23, 2008