Show/Hide Menu
Hide/Show Apps
anonymousUser
Logout
Türkçe
Türkçe
Search
Search
Login
Login
OpenMETU
OpenMETU
About
About
Açık Bilim Politikası
Açık Bilim Politikası
Frequently Asked Questions
Frequently Asked Questions
Browse
Browse
By Issue Date
By Issue Date
Authors
Authors
Titles
Titles
Subjects
Subjects
Communities & Collections
Communities & Collections
Modulation of human flavin-containing monooxygenase 3 activity by tricyclic antidepressants and other agents: Importance of residue 428
Date
1998-10-01
Author
Adalı, Orhan
Carver, GC
Philpot, RM
Metadata
Show full item record
This work is licensed under a
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
.
Item Usage Stats
0
views
0
downloads
Human flavin-containing monooxygenase 3 (FMO3) is subject to modulation by tricyclic antidepressants and other agents. Imipramine activates FMO3-catalyzed metabolism of methimazole at all substrate concentrations tested. This distinguishes FMO3 from rabbit FMO1 and FMO2, which are activated at high substrate concentration and inhibited at low substrate concentration, and pig FMO1, which is inhibited at all substrate concentrations. The response of FMO3 is also unique in that chlorpromazine is markedly more effective as a modulator than is imipramine. n-Octylamine,MgCl2, and HgCl2 all inhibit FMO3, the frst two in a biphasic manner. Substitution of lysine for threonine at position 428 significantly alters the response of FMO3 to modulators without changing the kinetic parameters for the metabolism of the substrate. Activation by imipramine and chlorpromazine is reduced or abolished and inhibition, most obvious at low substrate concentrations, is observed. This is consistent with elimination of self-activation in the metabolism of imipramine. The mutation at 428 also eliminates the biphasic nature of the inhibition by n-octylamine and MgCl2, but does not alter the effect of HgCl2. Our findings show that the activity of FMO3 can be modulated by large drug molecules as well as short-chain amines and metal ions. This modulation can be markedly altered by changing a single amino acid in the enzyme. (C) 1998 Academic Press.
Subject Keywords
Biophysics
,
Biochemistry
,
Molecular Biology
URI
https://hdl.handle.net/11511/47500
Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
DOI
https://doi.org/10.1006/abbi.1998.0835
Collections
Department of Biology, Article