Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Reductive metabolism of carbon tetrachloride by human cytochromes P-450 reconstituted in phospholipid vesicles: mass spectral identification of trichloromethyl radical bound to dioleoyl phosphatidylcholine.

Authors
Trudell-JR; Bosterling-B; Trevor-AJ
Source
Proc Natl Acad Sci U.S.A. 1982 Apr; 79(8):2678-2682
NIOSHTIC No.
00187033
Abstract
A reconstituted vesicle system with human cytochrome-P-450 was used in an extensive study of the reductive metabolism of carbon- tetrachloride (56235) (CCl4). This study demonstrated that the major reductive metabolite of carbon-tetrachloride by cytochrome-P- 450 was the trichloromethyl free radical and that this free radical was able to bind to double bonds of fatty acyl chains of the phospholipids in the membrane surrounding cytochrome-P-450. The structural identification of the reactive free radical metabolite and the product of its addition to phospholipids was accomplished by use of a reconstituted system of human cytochrome-P-450, NADPH- cytochrome-P-450-reductase, and cytochrome-b5 in phospholipid vesicles. The reconstituted vesicles contained a mixture of dioleoyl- phosphatidylcholine and egg phosphatidylethanolamine that served as both structural components and targets for trichloromethyl free radical binding. After incubation of these vesicles under a nitrogen atmosphere in the presence of NADPH with carbon-14 (C-14) labeled CCl4, the phospholipids were extracted and then separated by high performance liquid chromatography. The doleoyl- phosphatidylcholine fraction was transesterified and the resulting single C-14 labeled fatty acid methyl ester was purified by reverse phase chromatography. Desorption chemical ionization mass spectrometry with ammonia as reagent gas as well as desorption electron impact mass spectrometry permitted identification of the molecular structure as a mixture of 9 and 10 (trichloromethyl)stearate methyl esters.
Keywords
NIOSH-Publication; NIOSH-Grant; Grants-other; Metabolic-study; In-vitro-studies; Solvents; Chlorinated-hydrocarbons; Enzyme-activity
Contact
Anesthesia Stanford University Department of Anesthesia Stanford, Calif 94305
CODEN
PNASA6
CAS No.
56-23-5
Publication Date
19820415
Document Type
Journal Article
Funding Amount
1801197
Funding Type
Grant
Fiscal Year
1982
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-00978
Issue of Publication
8
ISSN
0027-8424
Priority Area
Other Occupational Concerns; Grants-other
Source Name
Proceedings of the National Academy of Sciences of the United States of America
State
CA
Performing Organization
Stanford University, Stanford, California
TOP