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

Details

• Personal Author:
  Bösterling B ; Trevor A ; Trudell JR
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Anesthesia Energy Metabolism Halothane Occupational Health Safety
• Keywords:
  Anesthetics Grants-other Halogenated-hydrocarbons Metabolic-study NIOSH-Grant NIOSH-Publication
• ISSN:
  0006-291X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  372-377
• Volume:
  102
• Issue:
  1
• NIOSHTIC Number:
  nn:00190474
• Citation:
  Biochem Biophys Res Commun 1981 Sep; 102(1):372-377
• Contact Point Address:
  Anesthesia Stanford University Department of Anesthesia Stanford, Calif 94305
• CAS Registry Number:
  (±)-Halothane (CAS RN 151-67-7)
• Federal Fiscal Year:
  1981
• NORA Priority Area:
  Other Occupational Concerns ; Grants Other
• Performing Organization:
  Stanford University, Stanford, California
• Peer Reviewed:
  True
• Start Date:
  19800901
• Source Full Name:
  Biochemical and Biophysical Research Communications
• End Date:
  19901130
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:719684ab1337a0ca555b188bda9833d052fc921c3587bdf1be996294e10a174f938bd8ab68ec6849d81518733aef3c791f4bbe75392d4d1160d48c2f80ae85d6
• Download URL:
  https://stacks.cdc.gov/view/cdc/203965/cdc_203965_DS1.pdf
• File Type:
  [PDF - 339.39 KB ]