UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Flavin-containing monooxygenase 3 (FMO3): genetic variants and their consequences for drug metabolism and disease

Phillips, I; Shephard, EA; (2020) Flavin-containing monooxygenase 3 (FMO3): genetic variants and their consequences for drug metabolism and disease. Xenobiotica , 50 (1) pp. 19-33. 10.1080/00498254.2019.1643515. Green open access

[thumbnail of Phillips Shephard Xenobiotica  2019 .pdf]
Preview
Text
Phillips Shephard Xenobiotica 2019 .pdf - Accepted Version

Download (538kB) | Preview

Abstract

1. The review focuses on genetic variants of human flavin-containing monooxygenase 3 (FMO3) and their impact on enzyme activity, drug metabolism and disease. // 2. The majority of FMO-mediated metabolism in adult human liver is catalyzed by FMO3. Some drugs are metabolized in human liver predominantly by FMO3, but most drug substrates of FMO3 are metabolized also by other enzymes, particularly cytochromes P-450, and the FMO3-catalyzed reaction is not the major route of metabolism. // 3. Rare variants that severely affect production or activity of FMO3 cause the disorder trimethylaminuria and impair metabolism of drug substrates of FMO3. More common variants, particularly p.[(Glu158Lys);(Glu308Gly)], can moderately affect activity of FMO3 in vitro and reduce metabolism of drug substrates in vivo, in some cases increasing drug efficacy or toxicity. // 4. Common variants of FMO3 have been associated with a number of disorders, but additional studies are needed to confirm or refute such associations. // 5. Elevated plasma concentrations of trimethylamine N-oxide, a product of an FMO3-catalyzed reaction, have been implicated in certain diseases, particularly cardiovascular disease. However, the evidence is often contradictory and additional work is required to establish whether trimethylamine N-oxide is a cause, effect or biomarker of the disease. // 6. Genetic variants of other FMOs are also briefly discussed.

Type: Article
Title: Flavin-containing monooxygenase 3 (FMO3): genetic variants and their consequences for drug metabolism and disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/00498254.2019.1643515
Publisher version: https://doi.org/10.1080/00498254.2019.1643515
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: allele frequency, cardiovascular disease, clinical effects, FMO1, FMO2, human, mutation, polymorphism, trimethylamine N-oxide, trimethylaminuria
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10078198
Downloads since deposit
485Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item