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

Flavin-Containing Monooxygenase 1 (FMO1) Catalyzes the Production of Taurine from Hypotaurine

Veeravalli, S; Phillips, IR; Freire, RT; Varshavi, D; Everett, JR; Shephard, EA; (2020) Flavin-Containing Monooxygenase 1 (FMO1) Catalyzes the Production of Taurine from Hypotaurine. Drug Metabolism and Disposition 10.1124/dmd.119.089995. (In press). Green open access

[img]
Preview
Text
dmd.119.089995.full.pdf - Accepted version

Download (609kB) | Preview

Abstract

Taurine is one of the most abundant amino acids in mammalian tissues. It is obtained from the diet and by de novo synthesis, from cysteic acid or hypotaurine. Despite the discovery in 1954 that the oxygenation of hypotaurine produces taurine, the identification of an enzyme catalyzing this reaction has remained elusive. In large part this is due to the incorrect assignment, in 1962, of the enzyme as an NAD-dependent hypotaurine dehydrogenase. For more than 55 years the literature has continued to refer to this enzyme as such. Here we show, both in vivo and in vitro, that the enzyme that oxygenates hypotaurine to produce taurine is flavin-containing monooxygenase 1 (FMO1). Metabolite analysis of the urine of Fmo1-null mice by 1H NMR spectroscopy revealed a build-up of hypotaurine and a deficit of taurine in comparison with the concentrations of these compounds in the urine of wild-type mice. In vitro assays confirmed that human FMO1 catalyzes the conversion of hypotaurine to taurine utilizing either NADPH or NADH as co-factor. FMO1 has a wide substrate range and is best known as a xenobiotic- or drug-metabolizing enzyme. The identification that the endogenous molecule hypotaurine is a substrate for the FMO1-catalyzed production of taurine resolves a long-standing mystery. This finding should help establish the role FMO1 plays in a range of biological processes in which taurine or its deficiency is implicated, including conjugation of bile acids, neurotransmitter, anti-oxidant and anti-inflammatory functions, and the pathogenesis of obesity and skeletal muscle disorders.

Type: Article
Title: Flavin-Containing Monooxygenase 1 (FMO1) Catalyzes the Production of Taurine from Hypotaurine
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1124/dmd.119.089995
Publisher version: https://doi.org/10.1124/dmd.119.089995
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: NMR, animal models, flavin-containing monooxygenase/FMO, genetically modified animal models
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Education
UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education
UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education > IOE - Social Research Institute
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/10093637
Downloads since deposit
3Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item