Faller T H, Csanády G A, Kreuzer P E, Baur C M, Filser J G
GSF-Institut für Toxikologie, Neuherberg, Germany.
Toxicol Appl Pharmacol. 2001 Apr 1;172(1):62-74. doi: 10.1006/taap.2001.9135.
Kinetics of the metabolic inactivation of 1,2-epoxypropane (propylene oxide; PO) catalyzed by glutathione S-transferase (GST) and by epoxide hydrolase (EH) were investigated at 37 degrees C in cytosol and microsomes of liver and lung of B6C3F1 mice, F344 rats, and humans and of respiratory and olfactory nasal mucosa of F344 rats. In all of these tissues, GST and EH activities were detected. GST activity for PO was found in cytosolic fractions exclusively. EH activity for PO could be determined only in microsomes, with the exception of human livers where some cytosolic activity also occurred, representing 1-3% of the corresponding GST activity. For GST, the ratio of the maximum metabolic rate (V(max)) to the apparent Michaelis constant (K(m)) could be quantified for all tissues. In liver and lung, these ratios ranged from 12 (human liver) to 106 microl/min/mg protein (mouse lung). Corresponding values for EH ranged from 4.4 (mouse liver) to 46 (human lung). The lowest V(max) value for EH was found in mouse lung (7.1 nmol/min/mg protein); the highest was found in human liver (80 nmol/min/mg protein). K(m) values for EH-mediated PO hydrolysis in liver and lung ranged from 0.83 (human lung) to 3.7 mmol/L (mouse liver). With respect to liver and lung, the highest V(max)/K(m) ratios were obtained for GST in mouse and for EH in human tissues. GST activities were higher in lung than in liver of mouse and human and were alike in both rat tissues. Species-specific EH activities in lung were similar to those in liver. In rat nasal mucosa, GST and EH activities were much higher than in rat liver.
在37摄氏度下，研究了谷胱甘肽S-转移酶（GST）和环氧水解酶（EH）催化1,2-环氧丙烷（环氧丙烷；PO）在B6C3F1小鼠、F344大鼠和人类的肝脏和肺组织以及F344大鼠的呼吸道和嗅鼻黏膜的胞质溶胶和微粒体中的代谢失活动力学。在所有这些组织中均检测到GST和EH活性。PO的GST活性仅在胞质组分中发现。PO的EH活性仅能在微粒体中测定，但人肝脏除外，人肝脏中也有一些胞质活性，占相应GST活性的1-3%。对于GST，可对所有组织定量最大代谢率（V(max)）与表观米氏常数（K(m)）的比值。在肝脏和肺中，这些比值范围从12（人肝脏）到106微升/分钟/毫克蛋白质（小鼠肺）。EH的相应值范围从4.4（小鼠肝脏）到46（人肺）。EH的最低V(max)值在小鼠肺中发现（7.1纳摩尔/分钟/毫克蛋白质）；最高值在人肝脏中发现（80纳摩尔/分钟/毫克蛋白质）。肝脏和肺中EH介导的PO水解的K(m)值范围从0.83（人肺）到3.7毫摩尔/升（小鼠肝脏）。就肝脏和肺而言，小鼠组织中GST以及人类组织中EH的V(max)/K(m)比值最高。小鼠和人类的肺中GST活性高于肝脏，大鼠的两种组织中GST活性相似。肺中物种特异性的EH活性与肝脏中的相似。在大鼠鼻黏膜中，GST和EH活性远高于大鼠肝脏。
