Comai K, Sullivan A C
J Pharm Sci. 1982 Apr;71(4):418-21. doi: 10.1002/jps.2600710411.
Methodology for the preparation of rat and human pancreatic lipase (EC 3.1.1.3) is described, which resulted in good yield of partially purified, stable enzyme useful for kinetic studies. Apparent Km values for the rat (6.5 mM) and human (3.5 mM) enzyme were determined with triolein as the substrate. Several compounds of the phenethylamine class were found to be inhibitors of both rat and human pancreatic lipase. The structural feature in the phenethylamine series tested, which appeared to be necessary for lipase inhibition, was a halogenated substituent on the 3 or 4 position of the aromatic ring as in flutiorex, fenfluramine, N-benzyl-beta-methoxy-3-(trifluoromethyl)phenethylamine (I), chlorphentermine and p-chloroamphetamine. A chloro group at the 2 position was ineffective (chlortermine). Alterations in the ethylamine portion of the molecule did not cause significant changes in the inhibitory properties of the active phenethylamines.
本文描述了大鼠和人胰脂肪酶（EC 3.1.1.3）的制备方法，该方法可获得较高产量的部分纯化且稳定的酶，可用于动力学研究。以三油酸甘油酯为底物测定了大鼠（6.5 mM）和人（3.5 mM）胰脂肪酶的表观米氏常数。发现几种苯乙胺类化合物是大鼠和人胰脂肪酶的抑制剂。在测试的苯乙胺系列中，似乎对脂肪酶抑制作用必需的结构特征是芳香环3或4位上的卤代取代基，如氟西汀、芬氟拉明、N-苄基-β-甲氧基-3-（三氟甲基）苯乙胺（I）、氯苯丁胺和对氯苯丙胺。2位上的氯基团无效（氯丁胺）。分子乙胺部分的改变不会导致活性苯乙胺抑制特性的显著变化。
