Reszka K J, Matuszak Z, Chignell C F, Dillon J
Department of Ophthalmology, Columbia University, New York, NY, USA.
Free Radic Biol Med. 1999 Mar;26(5-6):669-78. doi: 10.1016/s0891-5849(98)00244-5.
We report that a lactoperoxidase (LPO) metabolite derived from nitrite (NO2-) catalyses one-electron oxidation of biological electron donors and antioxidants such as NADH, NADPH, cysteine, glutathione, ascorbate, and Trolox C. The radical products of the reaction have been detected and identified using either direct EPR or EPR combined with spin trapping. While LPO/H2O2 alone generated only minute amounts of radicals from these compounds, the yield of radicals increased sharply when nitrite was also present. In aerated buffer (pH 7) the nitrite-dependent oxidation of NAD(P)H by LPO/H2O2 produced superoxide radical, O2*-, which was detected as a DMPO/*O2H adduct. We propose that in the LPO/H2O2/NO2-/biological electron donor systems the nitrite functions as a catalyst because of its preferential oxidation by LPO to a strongly oxidizing metabolite, most likely a nitrogen dioxide radical *NO2, which then reacts with the biological substrates more efficiently than does LPO/H2O2 alone. Because both nitrite and peroxidase enzymes are ubiquitous our observations point at a possible mechanism through which nitrite might exert its biological and cytotoxic action in vivo, and identify some of the physiological targets which might be affected by the peroxidase/H2O2/nitrite systems.
我们报告称，一种由亚硝酸盐（NO2-）衍生的乳过氧化物酶（LPO）代谢产物可催化生物电子供体和抗氧化剂（如NADH、NADPH、半胱氨酸、谷胱甘肽、抗坏血酸和Trolox C）的单电子氧化。反应的自由基产物已通过直接电子顺磁共振（EPR）或EPR结合自旋捕集技术进行了检测和鉴定。虽然单独的LPO/H2O2仅从这些化合物中产生微量自由基，但当同时存在亚硝酸盐时，自由基的产量会急剧增加。在通气缓冲液（pH 7）中，LPO/H2O2介导的亚硝酸盐依赖的NAD(P)H氧化产生超氧自由基O2* -，它被检测为DMPO/O2H加合物。我们提出，在LPO/H2O2/NO2-/生物电子供体系统中，亚硝酸盐起到催化剂的作用，因为它优先被LPO氧化为一种强氧化性代谢产物，很可能是二氧化氮自由基NO2，然后它与生物底物的反应比单独的LPO/H2O2更有效。由于亚硝酸盐和过氧化物酶在生物体内普遍存在，我们的观察结果指出了亚硝酸盐在体内可能发挥其生物学和细胞毒性作用的一种机制，并确定了一些可能受该过氧化物酶/H2O2/亚硝酸盐系统影响的生理靶点。
