title: Macular degeneration: a possible biochemical mechanism.
abstract: The possible role of labile endogenous metabolites in the cause of various chronic debilitating diseases such as macular degeneration has not been adequately explored. In the metabolism of the various retinoids, namely retinal (vitamin A aldehyde), retinol (vitamin A alcohol) and retinoic acid, each has the potential for generating labile intermediates, such as their corresponding 5,6-epoxides by the action of various cytochrome P(450)s. Such retinoid epoxides may well have the capacity for acting as toxins upon the neurons in the macula unless they are rapidly hydrolyzed by epoxide hydrolases. Since the cytochrome P(450)s responsible for epoxide formation and the various epoxide hydrolases involved in their hydrolysis are determined genetically, this may serve to explain a genetic component being involved in the causation of age-related macular degeneration.
authors.affiliation: Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, 500 W 12th Ave., The Ohio State University, Columbus, OH 43210, USA. soloway.1@osu.edu
authors.forename: Albert H
authors.initials: AH
authors.lastname: Soloway
authors.forename: Robert W
authors.initials: RW
authors.lastname: Curley
authors.forename: Scott M
authors.initials: SM
authors.lastname: Soloway
mesh_terms: D001671:Biochemistry / Q000379:methods; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D004851:Epoxide Hydrolases / Q000378:metabolism; D004852:Epoxy Compounds / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D008268:Macular Degeneration / Q000378:metabolism* / Q000473:pathology*; D008956:Models, Chemical; D008957:Models, Genetic; D009422:Nervous System Diseases / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D012172:Retinaldehyde / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism
chemical_list: D004852:Epoxy Compounds; D014801:Vitamin A; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases; D012172:Retinaldehyde