Sundheimer D W, Brendel K
Drug Metab Dispos. 1983 Sep-Oct;11(5):433-40.
The conjugation of harmol and the disposition of harmol metabolites by isolated rat hepatocytes were investigated. Harmol sulfation was saturated at very low concentrations and exhibited a maximum velocity of 1.2 +/- 0.2 nmol/min/10(6) hepatocytes. Glucuronidation of harmol proceeded with a Km of 17 +/- 5.7 microM and a maximal velocity of 2.1 +/- 0.3 nmol/min/10(6) hepatocytes. After synthesis, harmol glucuronide and harmol sulfate were distributed between cells and incubation media, and at equilibrium, a large concentration gradient between cells and media existed for both conjugates. Experiments with preformed metabolites indicated that hepatocytes removed harmol glucuronide from the incubation media by single Michaelis-Menten process with a Km of 384 +/- 63 microM and Vmax of 1.8 +/- 0.3 nmol/min/10(6) hepatocytes. Harmol sulfate was taken up by two Michaelis-Menten processes, a high affinity process with a Km of 33 +/- 8 microM and a Vmax of 0.97 +/- 0.2 nmol/min/10(6) cells and a low affinity process with a Km of 452 +/- 71 microM and Vmax of 25.2 +/- 4.1/min/10(6) hepatocytes. Harmol sulfate was released from hepatocytes by a process which did not exhibit saturation. Hepatocytes converted preformed harmol glucuronide to harmol sulfate.
研究了分离的大鼠肝细胞对去甲骆驼蓬碱的结合作用及其代谢产物的处置情况。去甲骆驼蓬碱的硫酸化在极低浓度下即达到饱和，最大速度为1.2±0.2 nmol/分钟/10⁶个肝细胞。去甲骆驼蓬碱的葡萄糖醛酸化反应的米氏常数（Km）为17±5.7 μM，最大速度为2.1±0.3 nmol/分钟/10⁶个肝细胞。合成后，去甲骆驼蓬碱葡萄糖醛酸苷和去甲骆驼蓬碱硫酸盐在细胞和孵育介质之间分布，平衡时，两种结合物在细胞和介质之间均存在较大的浓度梯度。对预先形成的代谢产物进行的实验表明，肝细胞通过单一的米氏过程从孵育介质中去除去甲骆驼蓬碱葡萄糖醛酸苷，米氏常数为384±63 μM，最大反应速度为1.8±0.3 nmol/分钟/10⁶个肝细胞。去甲骆驼蓬碱硫酸盐通过两个米氏过程被摄取，一个高亲和力过程，米氏常数为33±8 μM，最大反应速度为0.97±0.2 nmol/分钟/10⁶个细胞，另一个低亲和力过程，米氏常数为452±71 μM，最大反应速度为25.2±4.1/分钟/10⁶个肝细胞。去甲骆驼蓬碱硫酸盐通过一个未表现出饱和的过程从肝细胞中释放出来。肝细胞将预先形成的去甲骆驼蓬碱葡萄糖醛酸苷转化为去甲骆驼蓬碱硫酸盐。
