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Yeast Aldehyde Dehydrogenase Sensitivity to Inhibition by Chlorpropamide Analogues as an Indicator of Human Aldehyde Dehydrogenase Sensitivity to These Agents

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Enzymology and Molecular Biology of Carbonyl Metabolism 6

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 414))

Abstract

Aldehyde dehydrogenase (E.C. 1.2.1.3) is a polymorphic enzyme that is relatively substrate-nonspecific. Several isoenzymes are found in human tissues. Based on primary structure or subcellular distribution and kinetic, physical and immunochemical properties, they have been placed into one of three classes, viz., class 1, e.g., ALDH-1, class 2, e.g., ALDH-2 and class 3, e.g., ALDH-3 (Anonymous, 1989; Lindahl and Hempel, 1990; Goedde and Agarwal, 1990; Lindahl, 1992). These enzymes catalyze the biotransformation (bioactivation and/or bioinactivation) of a broad spectrum of endogenous (biogenic) and exogenous (xenobiotic) aldehydes that are physiologically and/or pharmacologically important (Sladek et al., 1989, 1995; Lindahl, 1992; Sladek, 1993, 1994). For example, ALDH-1 catalyzes the oxidation of retinaldehyde to retinoic acid, the latter being a potent modulator of cell growth and differentiation; ALDH-1 and, especially, ALDH-2 catalyze the oxidation of ethanol-derived acetaldehyde to acetate, a detoxifying reaction; ALDH-3 catalyzes the oxidation of 4-hydroxynonenal and other aldehydic products of lipid peroxidation to their corresponding acids, also a detoxifying reaction; and ALDH-1 and ALDH-3 catalyze the oxidation of aldophosphamide to carboxyphosphamide, yet another detoxifying reaction, since, alternatively, aldophosphamide, a metabolite of anticancer prodrugs collectively known as oxazaphosphorines, e.g., cyclophosphamide, gives rise to phosphoramide mustard, the metabolite that effects the cytotoxic action of these prodrugs.

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Authors and Affiliations

  1. Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, 55455, USA

    Varadahalli R. Devaraj, Lakshmaiah Sreerama & Norman E. Sladek

  2. Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota, 55455, USA

    Melinda J. C. Lee & Herbert T. Nagasawa

Authors
  1. Varadahalli R. Devaraj
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  2. Lakshmaiah Sreerama
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  3. Melinda J. C. Lee
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  4. Herbert T. Nagasawa
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  5. Norman E. Sladek
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Editors and Affiliations

  1. Purdue University, West Lafayette, Indiana, USA

    Henry Weiner

  2. University of South Dakota School of Medicine, Vermillion, South Dakota, USA

    Ronald Lindahl

  3. Indiana University School of Medicine, Indianapolis, Indiana, USA

    David W. Crabb

  4. Queen’s University, Kingston, Ontario, Canada

    T. Geoffrey Flynn

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Devaraj, V.R., Sreerama, L., Lee, M.J.C., Nagasawa, H.T., Sladek, N.E. (1996). Yeast Aldehyde Dehydrogenase Sensitivity to Inhibition by Chlorpropamide Analogues as an Indicator of Human Aldehyde Dehydrogenase Sensitivity to These Agents. In: Weiner, H., Lindahl, R., Crabb, D.W., Flynn, T.G. (eds) Enzymology and Molecular Biology of Carbonyl Metabolism 6. Advances in Experimental Medicine and Biology, vol 414. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5871-2_18

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  • DOI: https://doi.org/10.1007/978-1-4615-5871-2_18

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7692-7

  • Online ISBN: 978-1-4615-5871-2

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