Smith R C, Reed V D
Department of Animal and Dairy Sciences, Auburn University, Alabama 36849-5415.
Chem Biol Interact. 1992 Apr 15;82(2):209-17. doi: 10.1016/0009-2797(92)90111-w.
The ability of thiols, 2-imidazolethiones and uric acid to protect bovine oxyhemoglobin from copper(II)-induced oxidation to methemoglobin was investigated. The oxidation of oxyhemoglobin by Cu(II) proceeded in two phases: (1) an initial rapid reaction (less than 30 s) followed by (2) a slower reaction that carried it to completion. Thiols, including N-acetyl-L-cysteine, DL-dithiothreitol, reduced glutathione, DL-homocysteine, 2-mercaptoethanol and 2- and 3-mercaptopropionic acid, whose sulfhydryl groups were slowly oxidized by Cu(II) (with the exception of 2-mercaptopropionic acid), protected oxyhemoglobin in both phases of the reaction. Other thiols, including L-cysteine, cysteamine, and D-penicillamine, whose sulfhydryl groups were readily oxidized by Cu(II), protected hemoglobin initially, but within 2-4 min, the rate of methemoglobin formation was the same as Cu(II)-treated oxyhemoglobin. 2-Mercaptoimidazole and 1-methyl-2-mercaptoimidazole, which complex Cu(II) and inhibit Cu(II)-catalyzed oxidation of ascorbic acid, also protected hemoglobin in the initial phase, but not in the second phase. Uric acid, L-ergothioneine, and thiourea did not protect oxyhemoglobin in either the fast or slow phase. Cu(II) may have a coordination site involved in the oxidation of hemoglobin that is not blocked by the 2-imidazolethiones, uric acid, or the oxidized thiols. It is concluded that certain thiols that complex Cu(II) and are not rapidly oxidized will protect oxyhemoglobin from Cu(II)-induced oxidation, but the thiols are no longer effective once they are oxidized.
研究了硫醇、2-咪唑硫酮和尿酸保护牛氧合血红蛋白免受铜（II）诱导氧化为高铁血红蛋白的能力。铜（II）使氧合血红蛋白氧化分两个阶段进行：（1）初始快速反应（小于30秒），随后是（2）较慢的反应直至完成。硫醇，包括N-乙酰-L-半胱氨酸、二硫苏糖醇、还原型谷胱甘肽、DL-高半胱氨酸、2-巯基乙醇以及2-和3-巯基丙酸，其巯基被铜（II）缓慢氧化（2-巯基丙酸除外），在反应的两个阶段均能保护氧合血红蛋白。其他硫醇，包括L-半胱氨酸、半胱胺和D-青霉胺，其巯基易被铜（II）氧化，最初能保护血红蛋白，但在2-4分钟内，高铁血红蛋白的形成速率与经铜（II）处理的氧合血红蛋白相同。能与铜（II）络合并抑制铜（II）催化的抗坏血酸氧化的2-巯基咪唑和1-甲基-2-巯基咪唑，在初始阶段也能保护血红蛋白，但在第二阶段则不能。尿酸、L-麦角硫因和硫脲在快速或慢速阶段均不能保护氧合血红蛋白。铜（II）可能有一个参与血红蛋白氧化的配位位点，该位点不会被2-咪唑硫酮、尿酸或氧化的硫醇所阻断。得出的结论是，某些能与铜（II）络合并不会快速氧化的硫醇能保护氧合血红蛋白免受铜（II）诱导的氧化，但一旦被氧化，这些硫醇就不再有效。
