Lockerby D L, Rabin H R, Laishley E J
Antimicrob Agents Chemother. 1985 May;27(5):863-7. doi: 10.1128/AAC.27.5.863.
To demonstrate the importance of electron siphoning by the metronidazole reductase system from reduced ferredoxin to the mechanism of action of the drug in Clostridium pasteurianum, the effects of the reduction of metronidazole on the phosphoroclastic reaction were studied. Metronidazole concentrations between 0.5 and 5 mM caused a significant increase in acetyl phosphate production by the phosphoroclastic reaction compared to the control system without metronidazole. When this enzymatic reaction was assayed by standard manometric techniques under nitrogen gas, two simultaneous effects of electron siphoning were demonstrated: (i) the electrons from reduced ferredoxin were initially consumed for the reduction of metronidazole instead of being evolved as H2 via the ferredoxin-linked hydrogenase and (ii) phosphoroclastic activity was stimulated, with augmented production of CO2 and acetyl phosphate. This work further supports the notion of preferential scavenging of electrons away from ferredoxin-linked enzymatic reactions by metronidazole reductase(s) in C. pasteurianum.
为了证明在巴氏梭菌中，甲硝唑还原酶系统从还原型铁氧化还原蛋白进行电子虹吸对该药物作用机制的重要性，研究了甲硝唑还原对磷酸裂解反应的影响。与不含甲硝唑的对照系统相比，0.5至5 mM的甲硝唑浓度导致磷酸裂解反应产生的乙酰磷酸显著增加。当在氮气下通过标准测压技术测定这种酶促反应时，证明了电子虹吸的两种同时发生的作用：(i) 来自还原型铁氧化还原蛋白的电子最初用于还原甲硝唑，而不是通过与铁氧化还原蛋白相关的氢化酶以H2的形式释放；(ii) 磷酸裂解活性受到刺激，二氧化碳和乙酰磷酸的产生增加。这项工作进一步支持了在巴氏梭菌中甲硝唑还原酶优先从与铁氧化还原蛋白相关的酶促反应中清除电子的观点。
