Antholine W E, Taketa F
J Inorg Biochem. 1984 Jan;20(1):69-78. doi: 10.1016/0162-0134(84)80007-0.
1-Formylpyridine monothiosemicarbazonato copper II (CuL+) is readily taken up by red cells and is initially bound to glutathione and hemoglobin. Glutathione was depleted within 5 hr of incubation, presumably by oxidation mediated by CuL+ and O2 with concomitant generation of toxic oxygen species. Cupric ion was slowly transferred from CuL+ to hemoglobin within about 7 hr and hemoglobin was oxidized until the major form prevailing after 10 hr was alpha 2 beta 2+. Little increase in hemolysis due to addition of CuL+ dissolved in the radical scavenger dimethyl sulfoxide was observed with prolonged incubation. Strong inhibition of red cell hexokinase by CuL+ was observed when the enzymes in red cell lysates and hemoglobin-free red cell lysates were examined. CuL+ was also an effective inhibitor of yeast hexokinase. However, the inhibitory effect of CuL+ within the red cells was less pronounced. It is suggested that even though intracellular accumulation of CuL+ creates an oxidizing environment and is potentially capable of inhibiting thiol enzymes such as hexokinase, protective effects are exerted in the red cell by the presence of hemoglobin, of radical scavengers, and of high levels of enzymes that detoxify toxic oxygen species.
1-甲酰基吡啶单硫代氨基脲合铜（II）（CuL+）很容易被红细胞摄取，最初与谷胱甘肽和血红蛋白结合。在孵育5小时内谷胱甘肽被耗尽，推测是由CuL+和O2介导的氧化作用伴随有毒氧物种的产生所致。铜离子在大约7小时内从CuL+缓慢转移到血红蛋白，血红蛋白被氧化，直到10小时后占主导的主要形式为α2β2+。长时间孵育后，观察到由于添加溶解在自由基清除剂二甲基亚砜中的CuL+而导致的溶血增加很少。当检测红细胞裂解物和无血红蛋白的红细胞裂解物中的酶时，观察到CuL+对红细胞己糖激酶有强烈抑制作用。CuL+也是酵母己糖激酶的有效抑制剂。然而，CuL+在红细胞内的抑制作用不太明显。有人提出，尽管CuL+在细胞内积累会产生氧化环境并有可能抑制诸如己糖激酶等硫醇酶，但由于血红蛋白、自由基清除剂以及高水平的解毒有毒氧物种的酶的存在，红细胞中会产生保护作用。
