ISSN:
1432-0738
Keywords:
1,2-Epoxybutene-3
;
Butadiene monoxide
;
Microsomes
;
Cytosol
;
Pharmacokinetics
;
Mouse
;
Rat
;
Man
;
Epoxide hydrolase
;
Glutathione S-transferase
;
Cytochrome P-450-dependent monooxygenase
;
In vivo extrapolation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01973504
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