The effect of arginine-428 mutation on modulation of activity of human liver flavin monooxygenase 3 (FMO3) by imipramine and chlorpromazine

Date

1999-07-01

Author

Adalı, Orhan
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

223
views

0
downloads

This study was carried out to investigate the molecular basis for modulation of recombinant FMO3-catalyzed activity by the tricyclicantidepressants, imipramine and chlorpromazine. A mutant of human liver FMO3 (T428R) was formed by site-directed mutagenesis and characterized along with the native enzyme in order to elucidate a possible structure-function relationship. Functional properties of native and T428R human FMO3s were studied with methimazole as substrate. Both enzymes catalyzed the S-oxidation of methimazole with the same Km value. Imipramine modulated the activities of the native and T428R human FMO3s differently; the activity of the native FMO3 was increased at all concentrations, whereas the activity of the mutant enzyme was inhibited at concentrations above 300 mu M. Chlorpromazine activated the native enzyme at all concentrations of methimazole but activated the mutant enzyme only at high substrate concentrations. The direction (activation or inhibition) and extend of modulation of FMO3 activity is not only dependent on the concentration of the modulator, it is also dependent on the substrate concentration. This study confirms our previous findings with FMO1 that position 428 is important in the interaction of the FMO with modulators.

Subject Keywords

Flavin-containing monooxygenases, FMO3, Liver, Human, Imipramine, Chlorpromazine

URI

https://hdl.handle.net/11511/47341

Journal

EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY

DOI

https://doi.org/10.1016/s0940-2993(99)80004-9

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

The effect of cysteine-43 mutation on thermostability and kinetic properties of citrate synthase from Thermoplasma acidophilum Kocabıyık, Semra; Russel, RJM; Danson, MJ; Hough, DW (Elsevier BV, 1996-07-05) In this study, we have substituted serine-43 by cysteine in the recombinant citrate synthase from a moderately thermophilic Archaeon Thermoplasma acidophilum, for site-specific attachment of labels and have investigated the effects of this mutation on the biochemical properties and thermal stability of the enzyme. Both wild-type and the mutant enzymes were purified to homogenity using affinity chromatography on Matrex Gel Red A. The mutant Thermoplasma citrate synthase is very similar to wild-type citrate s...
The Effect of oxygen transfer conditions on recombinant glucose isomerase production by Pichia pastoris under glyceraldehyde-3-phosphate dehydrogenase promoter Güneş, Hande; Çalık, Pınar; Özdamar, Tunçer H.; Department of Chemical Engineering (2015) The aim of this study is to investigate effects of oxygen transfer conditions on recombinant glucose isomerase (r-GI) production by Pichia pastoris under glyceraldehyde-3-phosphate dehydrogenase promoter (PGAP). Two different sets of operation strategies were investigated in terms of oxygen transfer conditions. In the first one, aeration rate was kept constant at QO/V = 3 vvm, 6 vvm, and 10 vvm while agitation rate was kept at N = 900 rpm; and in the second one, dissolved oxygen concentration was kept const...
The impact of methionine, tryptophan and proline on methane (95%)-propane (5%) hydrate formation Longinos, Sotirios Nik; Longinou, Dimitra-Dionisia; Parlaktuna, Mahmut; Toktarbay, Zhexenbek (2021-10-01) This study examines the impact of three amino acids such as proline, methionine and tryptophan on methane (95%)-propane (5%) hydrate formation with the use of different impellers. The concentration of amino acids was 1 wt% at 24.5 bar and 2 degrees C. Based on experimental outcomes proline behaves as inhibitor and methionine and tryptophan perform as promoters. RT experiments both formed more quickly gas hydrates and indicated higher values in rate of hydrate formation compared to PBTU and PBTD experiments ...
The structural effects of Vitamin A deficiency on biological macromolecules due to ethanol consumption and withdrawal: An FTIR study with chemometrics ELİBOL, BİRSEN; Severcan, Mete; Jakubowska-Dogru, Ewa; DURSUN, İLKNUR; Severcan, Feride (2022-04-01) The structural effects of vitamin A-deficiency were examined on the molecular profiles of biomolecules of male rat hippocampus during prolonged ethanol intake/withdrawal using FT-IR spectroscopy coupled with chemometrics. Liquid ethanol diet with/without vitamin A was maintained to adult rats for 3-months. The rats were decapitated at different ethanol withdrawal times and FT-IR spectra were obtained. Ethanol consumption/withdrawal produced significant changes in proteins' conformations, while having insign...
The inhibitory effects of lindane in batch and upflow anaerobic sludge blanket reactors Bayramoğlu, Tuba Hande; Demirer, Göksel Niyazi (Elsevier BV, 2003-01-01) In this study, the inhibitory effects of lindane (LIN) on originally unacclimated mixed anaerobic cultures were investigated by anaerobic toxicity assay (ATA) experiments. ATA experiments revealed that 10 mg/l LIN exerted inhibitory effects on anaerobic cultures, which was recoverable. Continuous reactor experiments conducted to determine the inhibitory effects of LIN and the maximum LIN loading rate achievable in two-stage upflow anaerobic sludge blanket (UASB) reactors indicated that anaerobic granular cu...

Citation Formats

O. Adalı and R. Philpot, “The effect of arginine-428 mutation on modulation of activity of human liver flavin monooxygenase 3 (FMO3) by imipramine and chlorpromazine,” EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY, pp. 271–276, 1999, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/47341.