Xenobiotic Metabolic Enzymes: Bioactivation and Antioxidant Defense by Chang-Hwei Chen

Author:Chang-Hwei Chen
Language: eng
Format: epub
ISBN: 9783030416799
Publisher: Springer International Publishing

11.1.2 Endogenously Related Reactive Intermediates

Unlike exogenous metabolites that are derived from metabolism of foreign compounds like drugs, environmental chemicals, foods, and toxins, endogenously related reactive intermediates or metabolites are produced by organisms, such as metabolic products of amino acids, vitamins, and fatty acids. Compared to exogenous metabolites, oxidative stress mediated by endogenous metabolites has been less investigated, and the role of endogenous metabolites in various chronic diseases has not been adequately explored.

A typical example of endogenous metabolite-mediated chronic disease involves the metabolism of retinoids (retinal and retinol) and retinoic acid catalyzed by CYP450 enzymes, resulting in generation of epoxides as reactive intermediates. If such endogenous metabolites are not rapidly hydrolyzed by epoxide hydrolases , retinoid epoxides may act as toxicants to cause potential damage to the neurons in the macula. Genetic polymorphisms of CYP450 enzymes responsible for epoxide formation as well as epoxide hydrolases responsible for epoxides hydrolysis may serve to explain the involvement of genetic component in the process of age-related macular degeneration.

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