Physiological Substrates for Rat Alcohol Dehydrogenase Classes: Aldehydes of Lipid Peroxidation, ω-Hydroxyfatty Acids, and Retinoids

M. Dolors Boleda, Narcis Saubi, Jaume Farres, Xavier Pares

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173 Citations (Scopus)

Abstract

Alcohol dehydrogenase classes exhibit important differences in both substrate specificity and tissue distribution which suggest distinct physiological functions. We have studied the kinetic constants at pH 7.5 of the rat alcohol dehydrogenase classes, purified from liver (classes I and III) and from stomach (class IV), with three groups of relevant physiological compounds: Cytotoxic aldehydes generated in lipid peroxidation, ω-hydroxyfatty acids, and retinoids. Classes I and IV actively reduce 4-hydroxynonenal, 2-hexenal, and hexanal, which are toxic compounds known to be produced in significant amounts during lipid peroxidation. Class III shows poor activity with these aldehydes. Class IV exhibits the best k(cat)/K(m) values (2150 mM-1 · min-1 for 4-hydroxynonenal), which suggest a role for this enzyme in the elimination of the cytotoxic aldehydes in tissues that are susceptible to lipid peroxidation, such as skin, cornea, and mucosa of the respiratory and digestive tracts, where class IV is localized. The three classes are very active with ω-hydroxyfatty acids, suggesting that all of them are involved in the physiological oxidation of these compounds in the rat tissues. The kinetic constants support that oxidation of ω-hydroxyfatty acids is a physiological function for class III, in addition to its role as formaldehyde dehydrogenase. Finally, classes I and IV are active in retinol oxidation and retinal reduction. Class IV may play a crucial role in the generation of retinoic acid in epithelia, where this compound is involved in development and cell differentiation. In conclusion, alcohol dehydrogenase is an enzyme with multiple metabolic roles, and the different substrate specificity and tissue localization for each class provide organs and tissues with distinct physiological functions. © 1993 Academic Press, Inc.
Original languageEnglish
Pages (from-to)85-90
JournalArchives of Biochemistry and Biophysics
Volume307
Issue number1
DOIs
Publication statusPublished - 1 Jan 1993

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