The Alcohol Dehydrogenase System in the Rat: Comparison with the Human Enzyme
The rat is the most used animal model in studies on the metabolism and pharmacology of ethanol. The research on rat alcohol dehydrogenase (ADH; EC 220.127.116.11) started early (Markovic et al., 1971; Arslanian et al., 1971) and continued more recently (Crabb et al., 1983; Lad and Leffert, 1983, Mezey and Potter, 1983). These reports focused on the liver form that is most active with ethanol. During the last decade a great amount of information has been available on the human enzyme, which is now recognised to be a complex system of isoenzymes. The human ADH isoenzymes were grouped in three classes (I, II, III) according to their kinetic characteristics (Vallee and Bazzone, 1983). The rat, with only one ADH isoenzyme clearly described, appeared to be a model too simple for ethanol metabolism studies. We reinvestigated the rat enzyme in different organs and reported the existence of three distinct isoenzymes: ADH-3 is the liver enzyme with properties similar to human class I; ADH-2, present in all the organs examined, appeared homologous to human class III; ADH-1, isolated from stomach, exhibited characteristics of class II (Julià et al., 1987). Structural studies of classes I and III supported this classification (Julià et al., 1988). In the present report we summarize our work on the rat ADH isoenzymes and compare the rat and the human enzymes, taking into account the new human ADH that we have recently described in human stomach. We use the nomenclature of classes for the rat isoenzymes to allow a clear comparison with the human ADH.
KeywordsAlcohol Dehydrogenase Human Enzyme Human Class Distinct Isoenzyme Isoenzyme Class
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- Arsalanian, M.J., Pascoe, E. and Reinhold, J.G., 1971, Rat liver alcohol dehydrogenase. Purification and properties, Biochem. J., 125: 1039.Google Scholar
- Frolik, C.A., 1984, Metabolism of retinoids, In: “The retinoids,” Vol. 2, M.B. Sporn, A.B. Roberts, and Goodman, D.S., eds. Academic Press, Orlando.Google Scholar
- Holmes, R.S., 1988, Alcohol dehydrogenases and aldehyde dehydrogenases of anterior eye tissues from humans and other mammals, In: “Biomedical and social aspects of alcohol and alcoholism,” K. Kuriyama, A. Takada and H. Ishii, eds., Elsevier, Amsterdam.Google Scholar
- Moreno, A. and Parés, X., 1990, Purification and characterization of a new alcohol dehydrogenase from human stomach, J. Biol. Chem., 266: 1128.Google Scholar
- Pietruszko, R., 1979, Nonethanol substrates of alcohol dehydrogenase, In: “Biochemistry and pharmacology of ethanol,” Vol. 1, E. Majchrowicz and E.P. Noble, eds., Plenum Press, New York.Google Scholar
- Vallee, BL. and Bazzone, T.J., 1983, Isoenzymes of human liver alcohol dehydrogenase, Isozymes, Curr. Top. Biol. Med. Res., 8: 219.Google Scholar