title: Emerging roles of xenobiotic detoxification enzymes in metabolic diseases.
abstract: Mammalian systems have developed extensive molecular mechanisms to protect against the toxicity of many exogenous xenobiotic compounds. Interestingly, many detoxification enzymes, including cytochrome P450s and flavin-containing monooxygenases, and their associated transcriptional activators [e.g. the aryl hydrocarbon receptor (AhR)], have now been shown to have endogenous roles in normal physiology and the pathology of metabolic diseases. This mini-review will focus on two such instances: the role of flavin-containing monooxygenase 3 (FMO3) in the formation of the cardiometabolic disease biomarker trimethylamine-N-oxide (TMAO) and the role of AhR as a sensor of endogenous ligands such as those generated by the gut microbiota. Understanding the roles of xenobiotic sensing pathways in endogenous metabolism will undoubtedly lead to a better understanding of how exposure to environmental pollutants can perturb these physiological processes.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Petriello
authors.forename: Jessie B
authors.initials: JB
authors.lastname: Hoffman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hennig
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008024:Ligands; D008659:Metabolic Diseases / Q000139:chemically induced / Q000378:metabolism; D008744:Methylamines / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D008024:Ligands; D008744:Methylamines; D010105:Oxygenases; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C020066:dimethylaniline monooxygenase (N-oxide forming); C005855:trimethyloxamine