TY - JOUR
T1 - Reactivity of peroxynitrite versus simultaneous generation of ·NO and O2·- toward NADH
AU - Goldstein, S.
AU - Czapski, G.
PY - 2000
Y1 - 2000
N2 - The oxidation of NADH by peroxynitrite takes place indirectly via the radical intermediates formed during the self-decomposition of peroxynitrite, i.e., ·OH and ·NO2, and the oxidation yield exceeds 29% at relatively high NADH concentrations. The efficiency of oxidation of NADH by peroxynitrite is hardly affected by the presence of bicarbonate at physiological pH, and is remarkably increased when authentic peroxynitrite is replaced by low and equal fluxes of ·NO and O2·-. We determined the rate constants for the reactions of NADH with ·OH, CO3·-, and ·NO2 to be (2.0 ±0.2) x 1010, (1.4 ± 0.3) x 109, and (4.0 ±2.0) x 103 M--1 s--1, respectively. We show that the reaction of NADH with ·OH in aerated solution does not form O2·-, whereas the other one-electron oxidants oxidize NADH to NAD·, which in turn very efficiently reduces oxygen to O2·-. These results suggest that at physiological pH the oxidation of NADH by peroxynitrite in the absence or presence of bicarbonate occurs mainly through the reactions of NADH with ·OH or CO3·-, which are formed in about equal yields. The oxidation of NADH by continuous generation of ·NO and 02·- proceeds via a chain mechanism, and therefore, the oxidation yield increases upon decreasing the flux of the radicals, and is higher than that obtained with authentic peroxynitrite.
AB - The oxidation of NADH by peroxynitrite takes place indirectly via the radical intermediates formed during the self-decomposition of peroxynitrite, i.e., ·OH and ·NO2, and the oxidation yield exceeds 29% at relatively high NADH concentrations. The efficiency of oxidation of NADH by peroxynitrite is hardly affected by the presence of bicarbonate at physiological pH, and is remarkably increased when authentic peroxynitrite is replaced by low and equal fluxes of ·NO and O2·-. We determined the rate constants for the reactions of NADH with ·OH, CO3·-, and ·NO2 to be (2.0 ±0.2) x 1010, (1.4 ± 0.3) x 109, and (4.0 ±2.0) x 103 M--1 s--1, respectively. We show that the reaction of NADH with ·OH in aerated solution does not form O2·-, whereas the other one-electron oxidants oxidize NADH to NAD·, which in turn very efficiently reduces oxygen to O2·-. These results suggest that at physiological pH the oxidation of NADH by peroxynitrite in the absence or presence of bicarbonate occurs mainly through the reactions of NADH with ·OH or CO3·-, which are formed in about equal yields. The oxidation of NADH by continuous generation of ·NO and 02·- proceeds via a chain mechanism, and therefore, the oxidation yield increases upon decreasing the flux of the radicals, and is higher than that obtained with authentic peroxynitrite.
UR - http://www.scopus.com/inward/record.url?scp=0033845751&partnerID=8YFLogxK
U2 - 10.1021/tx000099n
DO - 10.1021/tx000099n
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C2 - 10956061
AN - SCOPUS:0033845751
SN - 0893-228X
VL - 13
SP - 736
EP - 741
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 8
ER -