扁桃酸在大鼠、小鼠和兔组织中的立体选择性代谢(英文)  

Stereoselective metabolism of mandelic acid in rat,mouse and rabbit tissue preparations

作　　者：高凌波[1] 王金朝[1,2] 姚彤炜[1] 曾苏[1] 

机构地区：[1]浙江大学药学院药物分析与代谢研究室,浙江杭州310058 [2]浙江华海药业股份有限公司质量控制部,浙江台州317024

出　　处：《中国药理学与毒理学杂志》2009年第5期351-356,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：supported by National Natural Science Foundation of China(30225047)~~

摘　　要：目的研究扁桃酸(MA)在大鼠、小鼠和兔组织中的立体选择性代谢,探讨MA代谢酶存在的部位、辅酶依赖性等性质以及可能的种属差异。方法MA对映体与大鼠、小鼠和兔的肝脏、肺、肾脏S9和微粒体共孵育,HPLC检测代谢并用柱前衍生化方法进行手性分析。同时考察辅酶NADH和NADPH及醇脱氢酶竞争性底物乙醇和抑制剂4-甲基吡唑对S-MA代谢的影响。结果S-MA在大鼠肝和肾S9中被代谢为PGA,而R-MA无代谢。两对映体在小鼠和兔组织中均不被代谢。乙醇和4-甲基吡唑不影响酶的活性,该代谢顺利进行的重要辅酶是NADPH而非NADH。结论大鼠中参与MA立体选择性代谢的酶是存在于胞浆或线粒体中的具有NADPH依赖性的非微粒体酶,而不是醇脱氢酶。MA的立体选择性代谢存在种属差异性。AIM To study in vitro stereoselective metabolism of mandelic acid （MA） in 3 kinds of laboratory animal tissue fractions and observe the differences of MA biotransformation. METHODS MA enantiomers were incubated with the tissue fractions from rats, mice and rabbits. The phenylglyoxylic acid （PGA） concentrations in incubation mixture were determined by high- performance liquid chromatography. Coenzymes and inhibitors were co-incubated with MA to investigate their effects on MA metabolism. RESULTS Only S-MA showed a unique metabolism in liver and kidneys $9 fractions of rats. No inhibition of the enzyme activity was observed by addition of ethanol or 4-methyl pyrazole. NAI）PH caused a remarkable increase in S-MA metabolism. CONCLUSION Nonmicrosomal enzymes in kidneys and liver except alcohol dehydrogenase are responsible for the stereoselective metabolism of MA in rats. The MA biotransformation is significantly different between rats and mice or rabbits.

关 键 词：扁桃酸类 苯乙酮类 代谢 微粒体 

分 类 号：R969[医药卫生—药理学]