Lipid-protein interactions as determinants of activation or inhibition by cytochrome b5 of cytochrome P-450-mediated oxidations

Details

• Personal Author:
  Bendix M ; Bosterling B ; Trevor AJ ; Trudell JR
• Description:
  Reconstituted cytochrome-P-450 systems were used to study the effects of cytochrome-b5 on the oxidation of a single substrate, benzphetamine (156081). Cytochrome-P-450 and NADPH-cytochrome-P-450- reductase were derived from livers of rabbits pretreated with phenobarbital. Micelle reconstituted systems and vesicle reconstituted systems were used. Variations in the molar ratio of NADPH-cytochrome-P-450-reductase to cytochrome-b5 to cytochrome-P- 450 and the ratios of proteins to phospholipids resulted in significant changes of metabolic activity. Depending on the system, cytochrome-b5 could be shown to exert no effect on benzphetamine N- demethylation, to cause almost complete inhibition of substrate oxidation, or to cause a three fold higher activity. These results were discussed in terms of a proposed model of lipid protein interactions. In the model, inhibition of cytochrome-P-450 mediated reactions resulted from changes in phospholipid/protein interactions and activation occurred via facilitation of electron transfer between NADPH-cytochrome-P-450-reductase and cytochrome-P-450 in the membrane. [Description provided by NIOSH]
• Subjects:
  Enzymes Occupational Health Safety
• Keywords:
  Enzyme-activity Grants-other In-vitro-studies Liver-microsomes Microsomal-enzymes NIOSH-Grant NIOSH-Publication
• ISSN:
  0021-9258
• 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
• Volume:
  257
• Issue:
  8
• NIOSHTIC Number:
  nn:00187017
• Citation:
  J Biol Chem 1982 Apr; 257(8):4375-4380
• Contact Point Address:
  Anesthesia Stanford University Department of Anesthesia Stanford, Calif 94305
• CAS Registry Number:
  Benzphetamine (CAS RN 156-08-1)
• Federal Fiscal Year:
  1982
• NORA Priority Area:
  Other Occupational Concerns ; Grants Other
• Performing Organization:
  Stanford University, Stanford, California
• Peer Reviewed:
  True
• Start Date:
  19800901
• Source Full Name:
  Journal of Biological Chemistry
• End Date:
  19901130
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f21610fe328dd3863b29c78570a16c7d432707695536e669ca34ab3aec0a4845c9a684d29628e5d07c11f6e476377191dc24a4fc64d7f61896156827b3559f68
• Download URL:
  https://stacks.cdc.gov/view/cdc/205029/cdc_205029_DS1.pdf
• File Type:
  [PDF - 1.23 MB ]