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1-chloro-2,2,2-trifluoroethyl radical: Formation from halothane by human cytochrome P-450 in reconstituted vesicles and binding to phospholipids.

Authors
Trudell-JR; Bosterling-B; Trevor-A
Source
Biochem Biophys Res Commun 1981 Sep; 102(1):372-377
NIOSHTIC No.
00190474
Abstract
Anaerobic metabolism of halothane (151677) was studied in vesicles composed of cytochrome-P-450, NADPH cytochrome-P-450-reductase, and cytochrome-b5 reconstituted in a mixture of dioleoylphosphatidylcholine and egg phosphatidylethanolamine. It was anticipated that free radicals of carbene metabolites formed from halothane would add to the single 9,10 double bond of the identical oleic-acid chains in dioleoylphosphatidylcholine. Significant covalent binding of radioactive metabolites to phospholipids was noted following incubation of reconstituted vesicles with carbon-14 labeled halothane under argon. A single peak of radioactivity was eluted at 23 minutes under conditions where methyl-oleate eluted at 26 minutes following transesterification of the dioleoylphosphatidylcholine fraction and separation of the methyl esters on a C18 reverse phase column. The findings were consistent with the addition of a CF3CHCl radical to the double bond of oleic-acid followed by abstraction of a hydrogen radical from a neighboring donor. Formation of a trifluoroethyl- carbene on cytochrome-P-450 following anaerobic incubation with halothane has been postulated. It is likely that a cyclopropane product resulting from addition of 2,2,2-trifluoroethyl-carbene to the 9,10 double bond of oleic-acid would be stable under the conditions of extraction and transesterification employed in this study. But, such an addition product was not found, suggesting that either the cytochrome P-450-carbene complex was so stable that it did not dissociate once formed, that the lifetime of the carbene was too short to diffuse to a double bond, or that the peak in absorption at 470 nanometers was not due to a carbene complex.
Keywords
NIOSH-Publication; NIOSH-Grant; Grants-other; Metabolic-study; Anesthetics; Halogenated-hydrocarbons
Contact
Anesthesia Stanford University Department of Anesthesia Stanford, Calif 94305
CODEN
BBRCA9
CAS No.
151-67-7
Publication Date
19810916
Document Type
Journal Article
Funding Amount
1801197.00
Funding Type
Grant
Fiscal Year
1981
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-00978
Issue of Publication
1
ISSN
0006-291X
Priority Area
Other Occupational Concerns; Grants-other
Source Name
Biochemical and Biophysical Research Communications
State
CA
Performing Organization
Stanford University, Stanford, California
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