title: In Vitro Metabolism of Flucetosulfuron by Human Liver Microsomes.
abstract: To investigate herbicide metabolism, human liver microsomes were incubated with threo- and erythro-isomers of flucetosulfuron. Each isomer produced one metabolite; the metabolites were unambiguously identified as enzymatic hydrolysis products by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). These metabolites were synthesized, producing white solids characterized using LC-MS/MS and nuclear magnetic resonance spectroscopy (1H and13C). Using specific esterase inhibitors and activators, carboxylesterases and cholinesterases were demonstrated to be involved in flucetosulfuron metabolism. Under optimized metabolic conditions, the kinetic parameters for metabolite formation from threo-flucetosulfuron and erythro-flucetosulfuron were: Vmax, 151.41 and 134.38 nmol/min/mg protein, respectively; Km, 2957.37 and 2798.53 μM, respectively; and CLint, 51.20 and 48.02 μL/min/mg microsomes respectively. No significant kinetic differences were observed between the two isomers. These results indicated that the primary metabolic pathway for both flucetosulfuron isomers in human liver microsomes involves hydrolysis, catalyzed by carboxylesterase and cholinesterase.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University , Seoul 151-742, South Korea.
authors.forename: Yong-Sang
authors.initials: YS
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University , Daegu 702-701, South Korea.
authors.forename: Kwang-Hyeon
authors.initials: KH
authors.lastname: Liu
authors.affiliation: Department of Plant Life and Environmental Sciences, Hankyong National University , Ansung 456-749, South Korea.
authors.forename: Joon-Kwan
authors.initials: JK
authors.lastname: Moon
authors.affiliation: Busan Branch of Forensic Chemistry Laboratory, Supreme Prosecutors' Office , Busan 611-743, South Korea.
authors.forename: Beom Jun
authors.initials: BJ
authors.lastname: Ko
authors.affiliation: Ministry of Food and Drug Safety , Cheongwon 363-951, South Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Choi
authors.affiliation: Specialty Chemicals Division, LG Life Sciences Ltd. , Ulsan 689-896, South Korea.
authors.forename: Kook-Sang
authors.initials: KS
authors.lastname: Hwang
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University , Seoul 151-742, South Korea.
authors.forename: Eunhye
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University , Seoul 151-742, South Korea.
authors.forename: Jeong-Han
authors.initials: JH
authors.lastname: Kim
keywords: esterase; flucetosulfuron; human liver microsomes; metabolism