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Enzyme specific kinetics of 1,2-epoxybutene-3 in microsomes and cytosol from livers of mouse, rat, and man.
Arch. Toxicol. 65, 59-67 (1991)
Kinetics of the metabolism of 1,2-epoxybutene-3 (butadiene monoxide) were investigated in liver fractions of mouse, rat, and man. In these species similar enzyme characteristics were found. In microsomes, no NADPH-dependent metabolism of butadiene monoxide was detectable. Epoxide hydrolase activity was found only in microsomes. The Vmax [nmol butadiene monoxide/(mg protein x min)] was 19 in mouse, 17 in rat, and 14 in man and the apparent Km (mmol butadiene monoxide/l incubate) was 1.5 in mouse, 0.7 in rat, and 0.5 in man. Glutathione S-transferase activity was found in cytosol only, revealing first order kinetics in the measured range. The ratio Vmax/Km [(nmol butadiene monoxide x l)/(mg protein × min × mmol of butadiene monoxide)] was 15 in mouse, 11 in rat, and 8 in man. The data obtained were used to extrapolate on the total rate of butadiene monoxide metabolism for each species in vivo: it was calculated to be 1.3 times higher in mice and 2.3 times lower in man compared to rats, when corrected for body weight.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
1,2-epoxybutene-3 ; Butadiene Monoxide ; Cytochrome P-450-dependent Monooxygenase ; Cytosol ; Epoxide Hydrolase ; Glutathione S-transferase ; In Vivo Extrapolation ; Man ; Microsomes ; Mouse ; Pharmacokinetics ; Rat
ISSN (print) / ISBN
0340-5761
e-ISSN
1432-0738
Journal
Archives of Toxicology
Quellenangaben
Volume: 65,
Issue: 1,
Pages: 59-67
Publisher
Springer
Reviewing status
Peer reviewed