Kinetics of propylene oxide metabolism in microsomes and cytosol of different organs from mouse, rat, and humans

被引:32
作者
Faller, TH
Csanády, GA
Kreuzer, PE
Baur, CM
Filser, JG
机构
[1] GSF, Inst Toxicol, D-85764 Neuherberg, Germany
[2] Tech Univ Munich, D-8000 Munich, Germany
[3] Univ Munich, Inst Rechts Med, D-8000 Munich, Germany
关键词
propylene oxide; microsomes; cytosol; liver; lung; nasal mucosa; mouse; rat; human; kinetics; closed-chamber technique;
D O I
10.1006/taap.2001.9135
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Kinetics of the metabolic inactivation of 1,2-epoxypropane (propylene oxide; PO) catalyzed by gluathione S-transferase (GST) and by epoxide hydrolase (EH) were investigated at 37 degreesC 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 mul/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, (C) 2001 Academic Press.
引用
收藏
页码:62 / 74
页数:13
相关论文
共 62 条
[1]  
Armstrong R N, 1994, Adv Enzymol Relat Areas Mol Biol, V69, P1
[2]   Kinetic and chemical mechanism of epoxide hydrolase [J].
Armstrong, RN .
DRUG METABOLISM REVIEWS, 1999, 31 (01) :71-86
[3]   THE CHARACTERIZATION OF GLUTATHIONE S-TRANSFERASES FROM RAT OLFACTORY EPITHELIUM [J].
BANGER, KK ;
LOCK, EA ;
REED, CJ .
BIOCHEMICAL JOURNAL, 1993, 290 :199-204
[4]   CYTOCHROME-P450 2A OF NASAL EPITHELIUM - REGULATION AND ROLE IN CARCINOGEN METABOLISM [J].
BEREZIAT, JC ;
RAFFALLI, F ;
SCHMEZER, P ;
FREI, E ;
GENESTE, O ;
LANG, MA .
MOLECULAR CARCINOGENESIS, 1995, 14 (02) :130-139
[5]  
BOND JA, 1983, CANCER RES, V43, P4805
[6]   In vivo and in vitro kinetics of ethylene oxide metabolism in rats and mice [J].
Brown, CD ;
Wong, BA ;
Fennell, TR .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1996, 136 (01) :8-19
[7]   ESTIMATING ERROR LIMITS IN PARAMETRIC CURVE FITTING [J].
CACECI, MS .
ANALYTICAL CHEMISTRY, 1989, 61 (20) :2324-2327
[8]   Pharmacokinetics and metabolism of vinyl fluoride in vivo and in vitro [J].
Cantoreggi, S ;
Keller, DA .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1997, 143 (01) :130-139
[9]   DIFFERENTIATION BETWEEN METABOLIC INCORPORATION AND COVALENT BINDING IN THE LABELING OF MACROMOLECULES IN THE RAT NASAL-MUCOSA AND BONE-MARROW BY INHALED [C-14] FORMALDEHYDE AND [H-3] FORMALDEHYDE [J].
CASANOVASCHMITZ, M ;
STARR, TB ;
HECK, HD .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1984, 76 (01) :26-44
[10]   BIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES IN NASAL EPITHELIUM OF RATS AFTER 3-DAY INTERMITTENT EXPOSURE TO FORMALDEHYDE AND OZONE ALONE OR IN COMBINATION [J].
CASSEE, FR ;
FERON, VJ .
TOXICOLOGY LETTERS, 1994, 72 (1-3) :257-268