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Review
. 2021 Jan 7;23(1):20.
doi: 10.1208/s12248-020-00536-y.

The Role of Alcohol Dehydrogenase in Drug Metabolism: Beyond Ethanol Oxidation

Li Di  1 , Amanda Balesano  2 , Samantha Jordan  2 , Sophia M Shi  3
Affiliations
Review

The Role of Alcohol Dehydrogenase in Drug Metabolism: Beyond Ethanol Oxidation

Li Di et al. AAPS J. .

Abstract

Alcohol dehydrogenases (ADHs) are most known for their roles in oxidation and elimination of ethanol. Although less known, ADHs also play a critical role in the metabolism of a number of drugs and metabolites that contain alcohol functional groups, such as abacavir (HIV/AIDS), hydroxyzine (antihistamine), and ethambutol (antituberculosis). ADHs consist of 7 gene family numbers and several genetic polymorphic forms. ADHs are cytosolic enzymes that are most abundantly found in the liver, although also present in other tissues including gastrointestinal tract and adipose. Marked species differences exist for ADHs including genes, proteins, enzymatic activity, and tissue distribution. The active site of ADHs is relatively small and cylindrical in shape. This results in somewhat narrow substrate specificity. Secondary alcohols are generally poor substrates for ADHs. In vitro-in vivo correlations for ADHs have not been established, partly due to insufficient clinical data. Fomepizole (4-methylpyrazole) is a nonspecific ADH inhibitor currently being used as an antidote for the treatment of methanol and ethylene glycol poisoning. Fomepizole also has the potential to treat intoxication of other substances of abuse by inhibiting ADHs to prevent formation of toxic metabolites. ADHs are inducible through farnesoid X receptor (FXR) and other transcription factors. Drug-drug interactions have been observed in the clinic for ADHs between ethanol and therapeutic drugs, and between fomepizole and ADH substrates. Future research in this area will provide additional insights about this class of complex, yet fascinating enzymes.

Keywords: ADH; Alcohol dehydrogenase; Drug metabolism; Drug-drug interactions; Genetic polymorphism; IVIVE; Species differences; Tissue distribution.

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References

    1. Edenberg HJ, McClintick JN. Alcohol dehydrogenases, aldehyde dehydrogenases, and alcohol use disorders: a critical review. Alcohol Clin Exp Res. 2018;42(12):2281–97. https://doi.org/10.1111/acer.13904 . - DOI - PubMed - PMC
    1. Edenberg HJ, Bosron WF. Alcohol dehydrogenases. In: McQueen CA, editor. Comprehensive toxicology. 3nd ed. Oxford: Elsevier; 2018. p. 126–39.
    1. Bhatt DK, Gaedigk A, Pearce RE, Leeder JS, Prasad B. Age-dependent protein abundance of cytosolic alcohol and aldehyde dehydrogenases in human liver. Drug Metab Dispos. 2017;45(9):1044–8,S1-S34. https://doi.org/10.1124/dmd.117.076463 . - DOI - PubMed - PMC
    1. Parkinson A, Ogilvie BW, Buckley DB, Kazmi F, Parkinson O. Biotransformation of xenobiotics. In: Klaassen C, editor. The basic science of poisons. 9th ed. New York: McGraw-Hill Education; 2018. p. 243.
    1. Yang Z-N, Bosron WF, Hurley TD. Structure of human χχ alcohol dehydrogenase: a glutathione-dependent formaldehyde dehydrogenase. J Mol Biol. 1997;265(3):330–43. https://doi.org/10.1006/jmbi.1996.0731 . - DOI - PubMed

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