Alcohol dehydrogenase (ADH) is a group of enzymes that initiate the breakdown of ethanol when it enters the human body. Understanding ADH provides insight into alcohol metabolism’s initial stages, impacting how individuals respond to alcoholic beverages. This enzymatic action is a fundamental part of the body’s detoxification process.
The Body’s Alcohol Processor
The primary function of alcohol dehydrogenase is to oxidize ethanol into a compound called acetaldehyde. This chemical reaction uses nicotinamide adenine dinucleotide (NAD+) as a coenzyme, converting ethanol into acetaldehyde and NAD+ into NADH. While reversible, the breakdown of ethanol is typically favored.
ADH enzymes are found in various tissues, with the highest activity concentrated in the liver, the main organ for metabolizing most consumed alcohol. ADH is also present in other areas, such as the stomach and intestines, contributing to initial processing before it reaches the liver. There are several forms of ADH, known as isoforms, including ADH1, ADH2, ADH3, ADH4, and ADH5, each with distinct functions.
Genetic and Individual Differences
Genetic variations in alcohol dehydrogenase (ADH) enzymes influence how quickly alcohol is metabolized. For example, certain variants of the ADH1B and ADH1C genes can lead to more active ADH enzymes, which break down alcohol into acetaldehyde at a faster pace. This rapid conversion can result in higher levels of acetaldehyde and may produce uncomfortable symptoms like flushing, nausea, and a rapid heartbeat.
These genetic differences contribute to varying levels of alcohol tolerance and susceptibility to its effects. For instance, the ADH1B2 allele is more common in East Asian populations and is associated with faster ethanol breakdown, which can discourage heavy drinking due to unpleasant symptoms. The ADH1B3 allele, found in people of African descent and some Native American tribes, also leads to a more rapid breakdown of alcohol. Gender and age can also influence ADH activity, but genetic variations are a primary determinant of individual metabolic rates.
Alcohol Dehydrogenase and Health
The activity of alcohol dehydrogenase has important implications for overall health, particularly due to the byproduct it creates. Acetaldehyde, produced by ADH, is a toxic compound and a known carcinogen. After ADH converts ethanol to acetaldehyde, another enzyme, aldehyde dehydrogenase (ALDH), then metabolizes acetaldehyde into acetate, a less harmful substance.
Efficient activity of both ADH and ALDH is important for minimizing the harm from acetaldehyde. If acetaldehyde accumulates due to less active ALDH, it can lead to symptoms associated with hangovers, such as facial flushing, nausea, and headaches. Individuals with genetic variants leading to less effective ALDH, like the inactive ALDH22 gene, often experience these adverse effects. While they may be less likely to develop alcoholism, they could face increased risks for certain cancers and liver damage if they consume alcohol regularly. Some medications, like disulfiram, specifically inhibit ALDH, causing acetaldehyde to build up and severe discomfort, used as a deterrent in alcohol treatment.