Nasal xenobiotic metabolizing enzymes: at the crossroads of toxicity, detoxification, and olfaction.

Enzymes exemplify the adaptability of biological systems through their multifunctional roles across tissues. Thus, xenobiotic metabolizing enzymes, traditionally recognized for their contributions to detoxification, biosynthesis, and signaling, also play specialized roles in the nasal cavity, where they encounter volatile compounds on a daily basis. In olfactory tissues, xenobiotic metabolizing enzymes act as odorant metabolizing enzymes, influencing not only volatile xenobiotic clearance but also sensory perception. These enzymes operate within a coordinated network of phase I, II, and III reactions, and are distributed across epithelial and neuronal cell types in both the olfactory and respiratory regions of the nasal cavity. Their expression patterns, activity, and regulatory dynamics suggest that xenobiotic metabolism can modulate olfactory function, with potential implications for toxicity, protection, and sensory modulation. This review first considers the risks posed by airborne xenobiotics and their impact on olfaction, then examines the function, expression, and regulation of odorant metabolizing enzymes, and finally highlights current experimental models and methodological advances that provide insights into xenobiotic and odorant metabolism in the nasal cavity.