S-methylation as a bioactivation mechanism for mono- and dithiocarbamate pesticides as aldehyde dehydrogenase inhibitors
作者:Richard E. Staub、Susan E. Sparks、Gary B. Quistad、John E. Casida
DOI:10.1021/tx00050a010
日期:1995.12
These soil fumigants are converted to S-methyl metam [MeNHC(S)SMe] which reaches peak levels in liver, kidney, brain, and blood 10-20 min after intraperitoneal (ip) treatment. The half-life of S-methyl metam administered ip is 8-12 min in each of these tissues. S-Methyl metam-oxon [MeNHC(O)SMe] is also detected as a metabolite of each of these soil fumigants on analysis by gas chromatography/mass spectrometry
S-甲基化是一种新的生物激活机制,可用于小鼠异硫氰酸甲酯和苯甲酰胺的代谢物和代谢产物。这些土壤熏蒸剂被转化为S-甲基metam [MeNHC(S)SMe],腹膜内(ip)处理10-20分钟后,其在肝,肾,脑和血液中达到峰值。在每个这些组织中,腹膜内注射的S-甲基元的半衰期为8-12分钟。通过气相色谱/质谱联用化学电离分析,还检测出S-甲基间甲氧还[MeNHC(O)SMe]作为这些土壤熏蒸剂的代谢产物。异硫氰酸甲酯向S-甲基间质的转化及其氧酮可能涉及与谷胱甘肽的结合,水解为S-(N-甲基硫代氨基甲酰基)-半胱氨酸,半胱氨酸共轭β-裂合酶裂解以释放间质,最后进行甲基化和氧化脱硫。通过用S-腺苷甲硫氨酸进行强化,小鼠肝脏微粒体将Metam和dazomet转化为S-甲基metam。腹腔注射40 mg / kg的小鼠的metam,异硫氰酸甲酯,dazomet和三种代谢物(metam-oxon [Me