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Reviews on Environmental Health

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Volume 32, Issue 1-2 (Mar 2017)


Emerging roles of xenobiotic detoxification enzymes in metabolic diseases

Michael C. Petriello
  • Superfund Research Center, University of Kentucky, 900 S. Limestone Street, Lexington, KY 40536, United States of America
  • Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40536, United States of America
  • Lexington Veterans Affairs Medical Center, Lexington Kentucky, United States of America
/ Jessie B. Hoffman
  • Superfund Research Center, University of Kentucky, 900 S. Limestone Street, Lexington, KY 40536, United States of America
  • Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536, United States of America
/ Andrew J. Morris
  • Corresponding author
  • Superfund Research Center, University of Kentucky, 900 S. Limestone Street, Lexington, KY 40536, United States of America
  • Lexington Veterans Affairs Medical Center, Lexington Kentucky, United States of America
  • Division of Cardiovascular Medicine, College of Medicine, University of Kentucky, Lexington, KY 40536, United States of America
  • Email:
/ Bernhard Hennig
  • Corresponding author
  • Superfund Research Center, University of Kentucky, 900 S. Limestone Street, Lexington, KY 40536, United States of America
  • Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40536, United States of America, Phone: +1 859-218-1343, Fax: +1 859-257-1811
  • Email:
Published Online: 2016-11-12 | DOI: https://doi.org/10.1515/reveh-2016-0050


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.

Keywords: cardiovascular disease; dioxin; FMO3; metabolic pathologies; TMAO


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About the article

Received: 2016-09-15

Accepted: 2016-09-30

Published Online: 2016-11-12

Published in Print: 2017-03-01

Research funding: This work was supported in part by the National Institute of Environmental Health Sciences at the National Institutes of Health [P42ES007380].

Conflict of interest: The authors declare that there are no competing financial interests.

Citation Information: Reviews on Environmental Health, ISSN (Online) 2191-0308, ISSN (Print) 0048-7554, DOI: https://doi.org/10.1515/reveh-2016-0050. Export Citation

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