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.
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This work was supported in part by the National Institute of Environmental Health Sciences at the National Institutes of Health [P42ES007380].
Petriello, Michael C.; Hoffman, Jessie B.; Morris, Andrew J.; and Hennig, Bernhard, "Emerging Roles of Xenobiotic Detoxification Enzymes in Metabolic Diseases" (2017). Superfund Research Center Faculty Publications. 2.