Ethanol oxidation is the process by which the human body breaks down alcohol, eliminating it from the system after consumption. The liver is the primary organ responsible for this breakdown, processing approximately 90% of the alcohol ingested. This process transforms ethanol into substances that can be more easily removed or utilized by the body.
The Main Pathway in the Body
The primary pathway for ethanol oxidation begins in the liver’s cytosol. Here, the enzyme alcohol dehydrogenase (ADH) initiates the conversion of ethanol (CH₃CH₂OH) into acetaldehyde (CH₃CHO). This reaction removes hydrogen atoms from ethanol, transferring them to nicotinamide adenine dinucleotide (NAD+), converting it to NADH.
Acetaldehyde, a highly toxic compound, is then processed. The enzyme aldehyde dehydrogenase (ALDH) converts acetaldehyde into acetate (CH₃COO⁻). This second reaction also involves the conversion of NAD+ to NADH. Acetate is a much less harmful substance that can be further metabolized by the body.
Other Important Pathways
While the ADH-ALDH pathway is the main route, the body employs other systems for ethanol oxidation. One significant alternative is the Microsomal Ethanol Oxidizing System (MEOS), primarily located in the liver’s endoplasmic reticulum. A key enzyme in MEOS is cytochrome P450 2E1 (CYP2E1). This system becomes more active, or “induced,” with chronic and heavy alcohol consumption.
A minor pathway involves the enzyme catalase, found in peroxisomes. This pathway contributes a small amount to overall alcohol metabolism, especially when alcohol concentrations are low. Its contribution is less significant compared to the ADH-ALDH pathway and MEOS.
The Impact of Oxidation Byproducts
The byproducts generated during ethanol oxidation have significant physiological effects. Acetaldehyde, the intermediate product formed from ethanol, is highly toxic to the body. Even short-term accumulation of acetaldehyde can cause many of the unpleasant symptoms associated with a “hangover,” such as nausea, headaches, and facial flushing. This is because acetaldehyde can dilate blood vessels, leading to the characteristic reddening of the skin.
Prolonged exposure to acetaldehyde contributes to more severe health issues. It forms adducts with proteins and DNA, interfering with normal cellular functions and repair mechanisms. This can lead to inflammation and oxidative stress, playing a role in the development of alcohol-related liver diseases like fatty liver, alcoholic hepatitis, and cirrhosis. Furthermore, acetaldehyde is classified as a carcinogen, increasing the risk of certain cancers, including those of the mouth, throat, esophagus, and liver. Acetate, the final product of the main oxidation pathway, is significantly less harmful and can be safely broken down into carbon dioxide and water or used as an energy source by various tissues in the body.
How Ethanol Oxidation Varies
The rate at which individuals process alcohol can vary considerably due to several factors. Genetic variations in the ADH and ALDH enzymes are a major influence. For example, some populations, particularly those of East Asian descent, have genetic variants that result in a highly active ADH enzyme and a less active or dysfunctional ALDH enzyme. This combination leads to a rapid conversion of ethanol to acetaldehyde, but a slow breakdown of acetaldehyde, causing it to accumulate quickly in the body. This accumulation manifests as the “Asian flush” syndrome, characterized by visible skin reddening, increased heart rate, and nausea, due to acetaldehyde toxicity.
Physiological factors also play a role in individual differences in ethanol oxidation. Gender can influence alcohol metabolism, with women typically having lower gastric ADH activity compared to men, which can lead to a higher blood alcohol concentration for the same amount of alcohol consumed. Body weight and overall liver health also affect how quickly alcohol is processed, as a larger body mass generally dilutes alcohol more, and a healthier liver can metabolize alcohol more efficiently. Additionally, factors like food consumption before drinking can slow alcohol absorption, and certain medications can interact with the enzymes involved in ethanol oxidation, altering its rate.