Registration is required for this free webinar
Hosted by the SOT Mechanisms Specialty Section
Cytochrome P450 2E1 (CYP2E1) is a highly conserved mammalian enzyme that sits at a key intersection of endogenous metabolism and xenobiotic bioactivation. Although it is best known for its high expression in pericentral hepatocytes, a growing body of work from our lab and others points to important roles outside the liver, particularly in the gut and the brain. In this talk, I will share new findings from the CYP2E1 knockout mouse model that reveal how loss of this enzyme disrupts liver homeostasis, alters gut epithelial biology, and influences signaling pathways that connect peripheral metabolic cues with the central nervous system. These changes involve mitochondrial function, lipid and ketone metabolism, aldehyde handling, and innate immune pathways, and together they create coordinated shifts across the liver-gut-brain axis. I will also discuss how these endogenous pathways intersect with environmental exposures. Pollutants that rely on CYP2E1 for bioactivation, including several widely encountered industrial solvents and volatile toxicants, are poised to interact with the same networks that are altered in the knockout. By integrating the knockout data with what is known about pollutant metabolism, I will outline a model in which CYP2E1 acts as a metabolic and toxicologic hub that shapes systemic physiology. The goal of this presentation is to highlight how endogenous metabolites such as acetone-derived methylglyoxal and exogenous toxicants converge on common biochemical pathways, and how this perspective broadens our understanding of CYP2E1 biology across tissues.
Speaker
Jessica Hartman, PhD, Assistant Professor, Medical University of South Carolina