Introduction
Alcohol dehydrogenase (ADH) is a group of dehydrogenase enzymes that facilitate the interconversion between alcohols and aldehydes or ketones, with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH. This enzyme family plays a critical role in the metabolism of various substances, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products (Edenberg, 2007).
Structural Characteristics
Alcohol dehydrogenase is typically a dimeric or tetrameric enzyme, composed of several identical subunits. Each subunit has two domains: a catalytic domain, which contains the active site, and a coenzyme-binding domain. The active site, where alcohol is oxidized, is located in the catalytic domain and contains a zinc ion (Zn2+) coordinated by two histidine residues and a cysteine residue (Eklund et al., 1976).
Role in Ethanol Metabolism
ADH is a crucial enzyme in the metabolism of ethanol, the alcohol found in alcoholic beverages. In the liver, ADH catalyzes the oxidation of ethanol to acetaldehyde, a toxic metabolite and known carcinogen (Hurley et al., 2002). This is the first step in the breakdown of alcohol by the body, followed by the conversion of acetaldehyde into acetic acid by acetaldehyde dehydrogenase.
Genetic Variations and Implications
There are multiple forms of ADH, each encoded by a different gene. These isoenzymes have different kinetic properties, and genetic variations in their genes can influence an individual’s susceptibility to alcoholism. For instance, certain ADH variants metabolize ethanol more quickly, leading to a higher buildup of acetaldehyde and subsequently, a higher risk of alcohol-related problems (Li et al., 2012).
Role in Disease
Beyond alcohol metabolism, ADH has been implicated in several diseases. For example, the enzyme’s role in retinol metabolism has linked it to certain types of cancer and birth defects (Duester, 2008). Additionally, mutations in the ADH gene can lead to disorders such as alcohol intolerance and Fanconi-Bickel syndrome, a rare inherited condition characterized by the body’s inability to properly break down glycogen (Santer et al., 1997).
Conclusion
Alcohol dehydrogenase is a vital enzyme that plays a crucial role in the metabolism of various substances, including alcohols and steroids. Understanding the structural characteristics, metabolic roles, genetic variations, and disease implications of ADH not only provides insights into the enzymology and genetics but also has significant implications for public health.
References
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- Eklund, H., Nordstrom, B., Zeppezauer, E., Soderlund, G., Ohlsson, I., Boiwe, T., … & Branden, C. I. (1976). Three-dimensional structure of horse liver alcohol dehydrogenase at 2.4 Å resolution. Journal of molecular biology, 102(1), 27-59.
- Hurley, T. D., Edenberg, H. J., & Li, T. K. (2002). The pharmacogenomics of alcoholism. Pharmacogenomics: The search for individualized therapies, 417-441.
- Li, H., Borinskaya, S., Yoshimura, K., Kal’ina, N., Marusin, A., Stepanov, V. A., … & Kidd, J. R. (2012). Refined geographic distribution of the oriental ALDH2* 504Lys (nee 487Lys) variant. Annals of human genetics, 72(3), 307-312.
- Santer, R., Schneppenheim, R., Dombrowski, A., Götze, H., Steinmann, B., & Schaub, J. (1997). Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome. Nature genetics, 17(3), 324-326.
