Church D L, Rabin H R, Laishley E J
Department of Microbiology, University of Calgary, Alberta, Canada.
J Antimicrob Chemother. 1990 Jan;25(1):15-23. doi: 10.1093/jac/25.1.15.
Highly-purified bidirectional hydrogenase (hydrogenase 1) of Clostridium pasteurianum could rapidly reduce several 2-, 4- and 5-nitroimidazole compounds via an electron carrier-coupled mechanism. Hydrogenase 1 was also shown to reduce a 2-nitroimidazole (misonidazole) and a 4-nitroimidazole in the presence of its required electron carriers including ferredoxin, the flavin coenzymes FAD and FMN, and the low potential electron carrier dyes methyl- and benzyl-viologen. No drug reduction by hydrogenase 1 occurred when any one of these electron carriers was replaced by nicotinamide electron carriers (NAD and NADP), or was omitted from the reaction mixture. The rates of reduction of the nitroimidazole compounds correlated with their one electron reduction potentials at pH 7(E7(1)); the higher the drug's E7(1), the faster its rate of reduction by the enzyme. Reduction rates for the drugs did not correlate with the antibacterial activity of these compounds against C. pasteurianum, suggesting that other factors are also important in determining the antimicrobial potencies of nitroimidazoles.
巴氏芽孢杆菌高度纯化的双向氢化酶（氢化酶1）可通过电子载体偶联机制快速还原多种2-、4-和5-硝基咪唑化合物。在其所需的电子载体（包括铁氧化还原蛋白、黄素辅酶FAD和FMN以及低电位电子载体染料甲基紫精和苄基紫精）存在的情况下，氢化酶1还可还原一种2-硝基咪唑（米索硝唑）和一种4-硝基咪唑。当这些电子载体中的任何一种被烟酰胺电子载体（NAD和NADP）取代，或从反应混合物中省略时，氢化酶1不会发生药物还原。硝基咪唑化合物的还原速率与其在pH 7时的单电子还原电位（E7(1)）相关；药物的E7(1)越高，其被该酶还原的速率越快。这些药物的还原速率与这些化合物对巴氏芽孢杆菌的抗菌活性无关，这表明其他因素在决定硝基咪唑的抗菌效力方面也很重要。
