Wallace K B, Dargan J E
Toxicol Appl Pharmacol. 1987 Sep 15;90(2):235-42. doi: 10.1016/0041-008x(87)90331-0.
The specific activities of hepatic enzymes involved in both the activation and detoxification of the anticholinesterase insecticide parathion were significantly greater in both rats and mice compared to either fathead minnows or rainbow trout. Whereas the rates of parathion desulfuration and hydrolysis were comparable, the specific activity for paraoxon hydrolysis was approximately threefold greater than its rate of formation for all species except trout. The kinetic data, however, indicate that the significantly greater Km for paraoxon hydrolysis limits its detoxification. Accordingly, the data are consistent with the progressive accumulation of this toxic metabolite in liver tissue incubated in vitro with parathion. The similar Km for parathion desulfuration and hydrolysis by rodents is consistent with the proposed mechanism of catalysis involving a common S-oxide intermediate. Due to the slow rates of enzyme catalysis, reliable kinetic estimates for the hydrolytic reactions were not possible for both species of fish. Assuming comparable Km values for paraoxon hydrolysis in rodents and fish, the net accumulation of paraoxon in tissue water may be quite similar between species and metabolic transformation may not be an important determinant of the species-selective toxicity of parathion.
与黑头呆鱼或虹鳟相比，参与抗胆碱酯酶杀虫剂对硫磷激活和解毒过程的肝脏酶的比活性在大鼠和小鼠中均显著更高。虽然对硫磷脱硫和水解的速率相当，但除鳟鱼外，所有物种对氧磷水解的比活性约比对氧磷形成速率高三倍。然而，动力学数据表明，对氧磷水解的显著更高的米氏常数限制了其解毒作用。因此，这些数据与在体外与对硫磷一起孵育的肝脏组织中这种有毒代谢物的逐步积累是一致的。啮齿动物对硫磷脱硫和水解的相似米氏常数与所提出的涉及共同S-氧化物中间体的催化机制一致。由于酶催化速率较慢，两种鱼类的水解反应无法获得可靠的动力学估计值。假设啮齿动物和鱼类对氧磷水解的米氏常数相当，组织水中对氧磷的净积累在物种之间可能非常相似，代谢转化可能不是对硫磷物种选择性毒性的重要决定因素。
