McCracken N W, Blain P G, Williams F M
Department of Pharmacological Sciences, Medical School, University of Newcastle upon Tyne, U.K.
Biochem Pharmacol. 1993 Jan 7;45(1):31-6. doi: 10.1016/0006-2952(93)90373-5.
In the present study, the distribution and nature of esterases in the rat which hydrolysed fluazifop-butyl, carbaryl, paraoxon and phenylacetate were investigated. Vmax and Km values for the hydrolysis reactions were determined. Fluazifop-butyl was hydrolysed to fluazifop by rat liver (Vmax mumol/min/g microsomes 6.2 +/- 0.4; cytosol 6.84 +/- 0.85), lung (Vmax microsomes 0.38 +/- 0.1; cytosol 1.5 +/- 0.32) and skin (Vmax microsomes 0.02 +/- 0.0015; cytosol 0.4 +/- 0.06) and by plasma (Vmax mumol/min/mL 5.8 +/- 0.48) and red blood cells (Vmax 0.03 +/- 0.015). Significant inhibition by paraoxon and bismitrophenol phosphate indicated the involvement of carboxylesterases. Carbaryl was hydrolysed by liver, lung and skin at a lower rate by microsomal fractions (Vmax nmol/min/g 2.1 +/- 0.25, 1.6 +/- 0.25, 0.2 +/- 0.035, respectively) compared to cytosolic fractions (Vmax 6.7 +/- 0.75, 1.4 +/- 0.36, 0.5 +/- 0.12) and plasma (Vmax nmol/min/mL 3.0 +/- 0.25). Hydrolysis involved carboxylesterases. Paraoxon was hydrolysed by paraoxonases/arylesterases only in the plasma (Vmax nmol/min/mL 246 +/- 12) and microsomal fractions from liver (Vmax 330 nmol/min/g +/- 25) and lung (Vmax 2 +/- 0.25). Phenylacetate was hydrolysed by both microsomal and cytosolic fractions from all tissues studied. Hydrolysis involved arylesterases in the microsomes and carboxylesterases in the cytosol. Extrahepatic hydrolysis may be important following some routes of exposure to xenobiotic esters.
在本研究中，对大鼠体内水解精稳杀得、西维因、对氧磷和苯乙酸酯的酯酶的分布及性质进行了研究。测定了水解反应的最大反应速度（Vmax）和米氏常数（Km）。精稳杀得被大鼠肝脏（Vmax：微摩尔/分钟/克微粒体为6.2±0.4；胞液为6.84±0.85）、肺（Vmax：微粒体为0.38±0.1；胞液为1.5±0.32）和皮肤（Vmax：微粒体为0.02±0.0015；胞液为0.4±0.06）以及血浆（Vmax：微摩尔/分钟/毫升为5.8±0.48）和红细胞（Vmax为0.03±0.015）水解为精稳杀得。对氧磷和磷酸二硝酚的显著抑制表明羧酸酯酶参与其中。西维因在肝脏、肺和皮肤中被微粒体部分（Vmax：纳摩尔/分钟/克分别为2.1±0.25、1.6±0.25、0.2±0.035）以低于胞液部分（Vmax为6.7±0.75、1.4±0.36、0.5±0.12）和血浆（Vmax：纳摩尔/分钟/毫升为3.0±0.25）的速度水解。水解涉及羧酸酯酶。对氧磷仅在血浆（Vmax：纳摩尔/分钟/毫升为246±12）以及肝脏（Vmax为330纳摩尔/分钟/克±25）和肺（Vmax为2±0.25）的微粒体部分被对氧磷酶/芳基酯酶水解。苯乙酸酯被所研究的所有组织的微粒体和胞液部分水解。水解在微粒体中涉及芳基酯酶，在胞液中涉及羧酸酯酶。在某些外源生物酯暴露途径之后，肝外水解可能很重要。
