DMD Large equally mixed donor pool

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


     

Drug Metabolism and Disposition Fast Forward
First published on November 16, 2004; DOI: 10.1124/dmd.104.000984

0090-9556/05/3302-214-218$20.00
DMD 33:214-218, 2005

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.104.000984v1
33/2/214    most recent
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 Google Scholar
Google Scholar
Right arrow Articles by Furnes, B.
Right arrow Articles by Schlenk, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Furnes, B.
Right arrow Articles by Schlenk, D.
SHORT COMMUNICATION

EXTRAHEPATIC METABOLISM OF CARBAMATE AND ORGANOPHOSPHATE THIOETHER COMPOUNDS BY THE FLAVIN-CONTAINING MONOOXYGENASE AND CYTOCHROME P450 SYSTEMS

Bjarte Furnes, and Daniel Schlenk

University of California, Riverside Riverside, California

The cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes are the major oxidative enzymes in phase I metabolism. Many organophosphate and carbamate thioether compounds are excellent substrates for these enzymes. Stereoselective sulfoxidation of fenthion and methiocarb by human liver, kidney, and microsomes was investigated. A high level of stereoselectivity in the formation of fenthion (+)-sulfoxide was observed in kidney and intestinal microsomes. This activity was not inhibited by the P450 inhibitor 1-aminobenzotriazole but was dramatically reduced following mild heat treatment. In liver, fenthion was metabolized to its sulfoxide in a nonstereoselective manner, and the activity was sensitive to both 1-aminobenzotriazole and heat treatment. The carbamate pesticide methiocarb also was sulfoxidated with a high degree of stereoselectivity in human kidney microsomes. Human liver microsomes formed both stereoisomers in equal amounts. Sulfoxide formation in kidney was not inhibited by 1-aminobenzotriazole but was abolished in liver microsomes. Formation of methiocarb sulfoxides was not observed in intestinal microsomes. The relative contribution of FMO1 and FMO3 to the sulfoxidation of carbophenothion, demeton-O, ethiofencarb, fonofos, and methiocarb also was investigated by using baculovirus-expressed recombinant proteins. FMO1 showed the highest catalytic activity for all pesticides. This study indicates that FMO1 may have a bigger role in extrahepatic metabolism than previously thought.

Address correspondence to: Dr. Daniel Schlenk, University of California, Riverside, 307 Science Laboratories I, Riverside, CA 92507. E-mail: daniel.schlenk{at}ucr.edu






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

Copyright © 2005 by the American Society for Pharmacology and Experimental Therapeutics.