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ID 38008
file
creator
Nakao, Miwako
Fujii, Kohyu
Kinoshita, Hiroyuki
Yuge, Osafumi
Morio, Michio
subject
Anesthetics; halothane
Biotransformation; trifluoroacetic acid
Microsomes; liver, guinea pig
NDC
Medical sciences
abstract
The formation of trifluoroacetic acid (TFAA) from halothane under aerobic conditions and that of chlorotrifluoroethane (CTE) and chlorodifluoroethylene (CDE) from halothane under anaerobic conditions were studied using guinea pig liver microsomes. The formation of TFAA was inhibited by specific inhibitors of cytochrome P450 (P450), such as carbon monoxide and metyrapone and was dependent upon P450 contents. The maximum activity of the TFAA formation was obtained at pH 6.0. On the other hand, the maximum activity to form CTE and CDE was obtained at pH 7.4. The formation of TFAA reached a plateau at a halothane concentration above 0.17 mM, but the rate of formation of CDE and CTE was dependent upon a halothane concentration up to 1.5 mM. The values of apparent Michaelis-Menten constant (Km) and maximum velocity (Vmax) for TFAA formation were 0.067 mM and 0.349 nmol/nmol P450/min respectively, those for CDE formation were 0.983 mM and 0.326 nmol/nmol P450/min respectively, and those for CTE formation were 1.71 mM and 0.752 nmol/nmol P450/min respectively. These results showed clearly that the formation of TFAA, CDE and CTE was catalyzed by the P450 system in guinea pig liver microsomes. Under optimal conditions, saturation was observed in the formation of TFAA from halothane at a halothane concentration above 0.17 mM but the formation of CDE and CTE was not saturated at this concentration, and the value of apparent Km for TFAA formation was lower than those for CDE and CTE formation.
description
This study was supported in part by a Grant-in-aid for Science Research from the Ministry of Education, Science and Culture of Japan and the Association for the Advancement of Medicine of the Tsuchiya Foundation.
journal title
Hiroshima Journal of Medical Sciences
volume
Volume 40
issue
Issue 1
start page
23
end page
28
date of issued
1991-03
publisher
Hiroshima University Medical Press
issn
0018-2052
ncid
pubmed id
language
eng
nii type
Departmental Bulletin Paper
HU type
Departmental Bulletin Papers
DCMI type
text
format
application/pdf
text version
publisher
department
Graduate School of Biomedical Science
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