Abstract
Flavin-containing monooxygenases (FMOs) catalyze the oxygenation of numerous foreign chemicals. This review considers the roles of FMOs in the metabolism of endogenous substrates and in physiological processes, and focuses on FMOs of human and mouse. Tyramine, phenethylamine, trimethylamine, cysteamine, methionine, lipoic acid and lipoamide have been identified as endogenous or dietary-derived substrates of FMOs in vitro. However, with the exception of trimethylamine, the role of FMOs in the metabolism of these compounds in vivo is unclear. The use, as experimental models, of knockout-mouse lines deficient in various Fmo genes has revealed previously unsuspected roles for FMOs in endogenous metabolic processes. FMO1 has been identified as a novel regulator of energy balance that acts to promote metabolic efficiency, and also as being involved in the biosynthesis of taurine, by catalyzing the S-oxygenation of hypotaurine. FMO5 has been identified as a regulator of metabolic ageing and glucose homeostasis that apparently acts by sensing or responding to gut bacteria. Thus, FMOs do not function only as xenobiotic-metabolizing enzymes and there is a risk that exposure to drugs and environmental chemicals that are substrates or inducers of FMOs would perturb the endogenous functions of these enzymes.
Highlights
Flavin-containing monooxygenases (FMOs; EC 1.14.13.8) are best known for their role in catalyzing the oxidative metabolism of numerous foreign chemicals, which include therapeutic drugs and environmental pollutants [1,2,3,4]
This review, considers the roles of FMOs in the metabolism of endogenous substrates and in physiological processes. It focuses on FMOs of human and mouse and how the use of genetically modified mouse models are contributing to our understanding of the endogenous roles of FMOs
The rate of fatty acid β-oxidation in skeletal muscle is higher in Fmo1−/−, Fmo2−/−, Fmo4−/− mice than in wild-type animals, which is likely to contribute to the enhanced whole-body energy expenditure and to depletion of stores of triglycerides in white adipose tissue (WAT) of the knockout animals
Summary
Flavin-containing monooxygenases (FMOs; EC 1.14.13.8) are best known for their role in catalyzing the oxidative metabolism of numerous foreign chemicals, which include therapeutic drugs and environmental pollutants [1,2,3,4]. In mouse the Fmo gene is highly expressed in adult liver [15,16]. The main site of expression in both human and mouse of the gene encoding FMO2 is the lung [2,16,18] (Table 1). The liver is the main site of expression of FMO3 in humans [10] (Table 1). It is expressed in skin [21], pancreas and in adrenal medulla and cortex [7]. The gene encoding FMO5 is expressed in pancreas [7] and in mouse in the kidney [16]
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