TY  - JOUR
AU  - Nagy, Péter
AU  - Jameson, GNL
AU  - Winterbourn, CC
TI  - Kinetics and Mechanisms of the Reaction of Hypothiocyanous Acid with 5-Thio-2-nitrobenzoic Acid and Reduced Glutathione
JF  - CHEMICAL RESEARCH IN TOXICOLOGY
J2  - CHEM RES TOXICOL
VL  - 22
PY  - 2009
IS  - 11
SP  - 1833
EP  - 1840
PG  - 8
SN  - 0893-228X
DO  - 10.1021/tx900249d
UR  - https://m2.mtmt.hu/api/publication/1498368
ID  - 1498368
N1  - Megjegyzés-21401573
Chemicals/CAS: benzoic acid, 532-32-1, 582-25-2, 65-85-0, 766-76-7; glutathione, 70-18-8; sodium chloride, 7647-14-5; thiol derivative, 13940-21-1; Glutathione, 70-18-8; Nitrobenzoates; Peroxidases, 1.11.1.-; Sulfhydryl Compounds; Thiocyanates; hypothiocyanite ion, 63296-34-4; hypothiocyanous acid; thionitrobenzoic acid, 15139-21-6
Megjegyzés-21401642
Chemicals/CAS: benzoic acid, 532-32-1, 582-25-2, 65-85-0, 766-76-7; glutathione, 70-18-8; sodium chloride, 7647-14-5; thiol derivative, 13940-21-1; Glutathione, 70-18-8; Nitrobenzoates; Peroxidases, 1.11.1.-; Sulfhydryl Compounds; Thiocyanates; hypothiocyanite ion, 63296-34-4; hypothiocyanous acid; thionitrobenzoic acid, 15139-21-6
AB  - Hypothiocyanite is a major oxidant generated by mammalian peroxidases. Although reported to react specifically with thiol groups in biological molecules, a detailed mechanistic study of this reaction has not been conducted. We have investigated the reaction of hypothiocyanous acid/ypothiocyanite with 5-thio-2-nitrobenzoic acid and with reduced glutathione by stopped-flow spectroscopy. The observed bell-shaped pH profile established that the reaction with 5-thio-2-nitrobenzoic acid proceeds via the thiolate and hypothiocyanous acid in the 2.5 < pH < 8 region. The obtained second-order rate constant of the reaction is (1.26 +/- 0.02) x 10(8) M-1 s(-1), and the effective rate constant at pH 7.4 is (4.37 +/- 0.03) x 10(5) M-1 s(-1), Analysis of the kinetic data, using a value of 4.38 +/- 0.01 for the pK(a) of 5-thio-2-nitrobenzoic acid thiol (measured independently by spectroscopic analysis), gave a pK(a) of 4.85 +/- 0.01 for hypothiocyanous acid at physiological salt concentration (I = 120 mM; NaCl and phosphate buffer) and 25 degrees C. A second-order rate constant of (8.0 +/- 0.5) x 10(4) M-1 s(-1) for the reaction of hypothiocyanous acid/hypothiocyanite with reduced glutathione at pH 7.4 was determined. The glutathione data are also consistent with the reaction proceeding via the thiolate and hypothiocyanous acid. Our results demonstrate that hypothiocyanous acid/hypothiocyanite has very high reactivity with thiols and will be short-lived in the presence of physiological concentrations of glutathione and thiol proteins. As the reaction occurs strictly with the thiolate, this oxidant should selectively target proteins containing low pK(a) thiols.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Geiszt, Miklós
AU  - Witta, J
AU  - Baffi, J
AU  - Lekstrom, K
AU  - Leto, TL
TI  - Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense
JF  - FASEB JOURNAL
J2  - FASEB J
VL  - 17
PY  - 2003
IS  - 9
SP  - 1502
EP  - 1504
PG  - 3
SN  - 0892-6638
DO  - 10.1096/fj.02-1104fje
UR  - https://m2.mtmt.hu/api/publication/1468168
ID  - 1468168
LA  - English
DB  - MTMT
ER  -