Doyle M P, Herman J G, Dykstra R L
J Free Radic Biol Med. 1985;1(2):145-53. doi: 10.1016/0748-5514(85)90019-4.
The nitrite ion is a direct causative agent for methemoglobinemia. Oxidation of hemoglobin to methemoglobin under aerobic conditions is induced by nitrite, catalyzed by methemoglobin in the presence of hydrogen peroxide, and inhibited by chemical reagents ranging from cysteine and ascorbic acid to sulfite. The stoichiometry of nitrate production is dependent on the initial [NO2-]/[HbO2] ratio, but reaches a limiting value of 1:1 [NO3-]: [Hb+] when [NO2-]/[HbO2] greater than 8. Ascorbic acid is an exceptionally effective inhibitor for the autocatalytic oxidation, but its use does not affect the stoichiometry of nitrate formation. Sulfite reduces nitrate production to a level that is half that observed in its absence. These chemical inhibitors act upon the rapid autocatalytic stage for hemoglobin oxidation, but they do not influence the slow direct oxidation of hemoglobin by nitrite. The autocatalytic stage for hemoglobin oxidation results from nitrogen dioxide formed from nitrite through the peroxidase activity of methemoglobin. Peroxide and methemoglobin are formed during the initiation stage by electron transfer from nitrite that is kinetically first order in oxyhemoglobin and in nitrite.
亚硝酸根离子是高铁血红蛋白血症的直接致病因子。在有氧条件下，亚硝酸可将血红蛋白氧化为高铁血红蛋白，在过氧化氢存在时由高铁血红蛋白催化，并受到从半胱氨酸、抗坏血酸到亚硫酸盐等化学试剂的抑制。硝酸盐生成的化学计量取决于初始的[NO2-]/[HbO2]比值，但当[NO2-]/[HbO2]大于8时，会达到1:1 [NO3-]: [Hb+]的极限值。抗坏血酸是自催化氧化的一种极其有效的抑制剂，但其使用并不影响硝酸盐形成的化学计量。亚硫酸盐可将硝酸盐生成量降低至无亚硫酸盐时观察到的一半水平。这些化学抑制剂作用于血红蛋白氧化的快速自催化阶段，但不影响亚硝酸对血红蛋白的缓慢直接氧化。血红蛋白氧化的自催化阶段是由亚硝酸通过高铁血红蛋白的过氧化物酶活性形成的二氧化氮导致的。在起始阶段，通过氧合血红蛋白和亚硝酸中亚硝酸根的电子转移形成过氧化物和高铁血红蛋白，这在动力学上是一级反应。
