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

Drug Metab Dispos. 2020 May;48(5):378-385. doi: 10.1124/dmd.119.089995.

Sunil Veeravalli ¹, Ian R Phillips ², Rafael T Freire ¹, Dorsa Varshavi ¹, Jeremy R Everett ³, Elizabeth A Shephard ⁴

Affiliations

1 Department of Structural and Molecular Biology, University College London, London, United Kingdom (S.V., I.R.P., E.A.S.); School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom (I.R.P.); and Medway Metabonomics Research Group, University of Greenwich, Chatham Maritime, Kent, United Kingdom (R.T.F., D.V., J.R.E.).
2 Department of Structural and Molecular Biology, University College London, London, United Kingdom (S.V., I.R.P., E.A.S.); School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom (I.R.P.); and Medway Metabonomics Research Group, University of Greenwich, Chatham Maritime, Kent, United Kingdom (R.T.F., D.V., J.R.E.) i.r.phillips@ucl.ac.uk.
3 Department of Structural and Molecular Biology, University College London, London, United Kingdom (S.V., I.R.P., E.A.S.); School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom (I.R.P.); and Medway Metabonomics Research Group, University of Greenwich, Chatham Maritime, Kent, United Kingdom (R.T.F., D.V., J.R.E.) j.r.everett@greenwich.ac.uk.
4 Department of Structural and Molecular Biology, University College London, London, United Kingdom (S.V., I.R.P., E.A.S.); School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom (I.R.P.); and Medway Metabonomics Research Group, University of Greenwich, Chatham Maritime, Kent, United Kingdom (R.T.F., D.V., J.R.E.) e.shephard@ucl.ac.uk.

PMID: 32156684 DOI: 10.1124/dmd.119.089995

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 (FMO) 1. Metabolite analysis of the urine of Fmo1-null mice by ¹H NMR spectroscopy revealed a buildup 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 cofactor. 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 biologic processes in which taurine or its deficiency is implicated, including conjugation of bile acids, neurotransmitter, antioxidant and anti-inflammatory functions, and the pathogenesis of obesity and skeletal muscle disorders. SIGNIFICANCE STATEMENT: The identity of the Enzyme that catalyzes the biosynthesis of taurine from hypotaurine has remained elusive. Here we show, both in vivo and in vitro, that flavin-containing monooxygenase 1 catalyzes the oxygenation of hypotaurine to produce taurine.

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