Veeravalli, Sunil, Phillips, Ian R., Freire, Rafael T., Varshavi, Dorsa, Everett, Jeremy ORCID: 0000-0003-1550-4482 and Shephard, Elizabeth A. (2020) Flavin-Containing Monooxygenase 1 (FMO1) catalyzes the production of taurine from hypotaurine. Drug Metabolism and Disposition, 48 (4). ISSN 0090-9556 (Print), 1521-009X (Online) (doi:https://doi.org/10.1124/dmd.119.089995)

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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 a 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 FMO1 of human 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, the pathogenesis of obesity and skeletal muscle disorders.

Item Type:	Article
Additional Information:	The article was also hosted on the bioRxiv pre-print server from 30th August 2019: https://www.biorxiv.org/content/10.1101/750273v1.
Uncontrolled Keywords:	metabonomics, metabolomics, taurine, hypotaurine, biosynthesis, medicine, humans, Drug Metabolism and Disposition, bioRxiv preprint server
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	19 Nov 2024 14:27
URI:	http://gala.gre.ac.uk/id/eprint/27419

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