DMD Celsis microsomes mean better data

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Khojasteh-Bakht, S. C.
Right arrow Articles by Nelson, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Khojasteh-Bakht, S. C.
Right arrow Articles by Nelson, S. D.

Vol. 26, Issue 7, 701-704, July 1998

(R)-(+)-Menthofuran Is a Potent, Mechanism-Based Inactivator of Human Liver Cytochrome P450 2A6

Siamak C. Khojasteh-Bakht, Luke L. Koenigs, Raimund M. Peter, William F. Trager, and Sidney D. Nelson

Department of Medicinal Chemistry, University of Washington

(R)-(+)-Menthofuran is a potent, mechanism-based inactivator of human liver cytochrome P450 (CYP or P450) 2A6. Menthofuran caused a time- and concentration-dependent loss of CYP2A6 activity. The inactivation of CYP2A6 was characterized by a Ki of 2.5 µM and a kinact of 0.22 min-1 for human liver microsomes and a Ki of 0.84 µM and a kinact of 0.25 min-1 for purified expressed CYP2A6. Addition of various nucleophiles, a chelator of iron, or scavengers of reactive oxygen species or extensive dialysis failed to protect CYP2A6 from inactivation. An antibody to metallothionein conjugates of a suspected reactive metabolite of menthofuran was used to detect reactive menthofuran metabolite adducts with CYP2A6. These adducts were formed only in the presence of NADPH-P450 reductase and NADPH. Glutathione, methoxylamine, and semicarbazide did not prevent adduction of reactive menthofuran metabolites to CYP2A6, however. The menthofuran metabolite formation/CYP2A6 inactivation partition ratio was determined to be 3.5 ± 0.6 nmol/nmol of P450. Menthofuran was unable to inactivate CYP1A2, CYP2D6, CYP2E1, or CYP3A4 in a time- and concentration-dependent manner.

Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
M. Miyazawa, A. Sugie, and T. Shimada
ROLES OF HUMAN CYP2A6 AND 2B6 AND RAT CYP2C11 AND 2B1 IN THE 10-HYDROXYLATION OF (-)-VERBENONE BY LIVER MICROSOMES
Drug Metab. Dispos., August 1, 2003; 31(8): 1049 - 1053.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
K.-i. Fujita and T. Kamataki
Screening Of Organosulfur Compounds as Inhibitors of Human CYP2A6
Drug Metab. Dispos., July 1, 2001; 29(7): 983 - 989.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
J. R. Palamanda, C. N. Casciano, L. A. Norton, R. P. Clement, L. V. Favreau, C.-c. Lin, and A. A. Nomeir
Mechanism-Based Inactivation of CYP2D6 by 5-Fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1-piperazinyl]pyrimidine
Drug Metab. Dispos., June 1, 2001; 29(6): 863 - 867.
[Abstract] [Full Text]

Home page
 Drug Metab. Dispos.Home page
P. Taavitsainen, R. Juvonen, and O. Pelkonen
In Vitro Inhibition of Cytochrome P450 Enzymes in Human Liver Microsomes by a Potent CYP2A6 inhibitor, trans-2-Phenylcyclopropylamine (Tranylcypromine), and Its Nonamine Analog, Cyclopropylbenzene
Drug Metab. Dispos., March 1, 2001; 29(3): 217 - 222.
[Abstract] [Full Text]

Home page
 Toxicol SciHome page
G. J. Diaz and E. J. Squires
Metabolism of 3-Methylindole by Porcine Liver Microsomes: Responsible Cytochrome P450 Enzymes
Toxicol. Sci., June 1, 2000; 55(2): 284 - 292.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. C. Khojasteh-Bakht, W. Chen, L. L. Koenigs, R. M. Peter, and S. D. Nelson
Metabolism of (R)-(+)-Pulegone and (R)-(+)-Menthofuran by Human Liver Cytochrome P-450s: Evidence for Formation of a Furan Epoxide
Drug Metab. Dispos., May 1, 1999; 27(5): 574 - 580.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1998 by the American Society for Pharmacology and Experimental Therapeutics.