Where is Alcohol Metabolized and How Does it Work?

Learn about how our body processes alcoholic beverages through a complex metabolic pathway involving several enzymes such as ADH & ALDH.

Where is Alcohol Metabolized and How Does it Work?

After swallowing alcohol, it is mainly absorbed from the small intestine into the veins that collect blood from the stomach and intestines and from the portal vein, which leads to the liver. From there it is carried to the liver, where it is exposed to enzymes and metabolized. Once alcohol is ingested, it is not digested like food. A small amount is absorbed directly by the tongue and mucous lining of the mouth.

In the stomach, alcohol is absorbed directly into the bloodstream through the tissue lining of the stomach and small intestine. There are two ways in which the liver can process alcohol. Most alcohol is broken down, or metabolized, by an enzyme in liver cells known as alcohol dehydrogenase (ADH). ADH breaks down alcohol into acetaldehyde, and then another enzyme, aldehyde dehydrogenase (ALDH), rapidly breaks down acetaldehyde into acetate.

Acetate is further metabolized and eventually leaves the body in the form of carbon dioxide and water. The cytoplasm of liver cells contains an enzyme called alcohol dehydrogenase (ADH) that catalyzes the oxidation of ethanol to acetaldehyde (Figure 1). Oxidation occurs when ethanol binds to a site of the ADH enzyme and loses some electrons in the form of H atoms. In reality, ethanol gives up two H atoms to another molecule that also binds to ADH.

This electron-receiving molecule is called a coenzyme. Without the coenzyme, the ADH enzyme will not work very well. Disulfiram is an FDA-approved drug that has been used to treat alcoholism since the 1940s and is perhaps still the most widely used drug in the United States today. Its main mode of action is as an aversive agent.

Disulfiram inhibits aldehyde dehydrogenase and prevents metabolism of the main metabolite of alcohol, acetaldehyde. In turn, the accumulation of acetaldehyde in the blood causes unpleasant effects if alcohol is ingested; these include sweating, headache, dyspnea, decreased blood pressure, hot flashes, sympathetic hyperactivity, palpitations, nausea and vomiting. The association of these symptoms with alcohol consumption discourages further consumption of alcohol. Serious side effects such as hepatitis, hepatotoxicity, depression and psychotic reactions have also been reported. When alcohol is consumed, it is absorbed into the blood from the stomach and intestines.

Then, enzymes begin to metabolize alcohol. Ethanol, an alcohol found in nature and in alcoholic beverages, is metabolized through a complex catabolic metabolic pathway. In humans, several enzymes are involved in processing ethanol first into acetaldehyde and then into acetic acid and acetyl-CoA. Once acetyl-CoA is formed, it becomes a substrate for the citric acid cycle, ultimately producing cellular energy and releasing water and carbon dioxide. Due to differences in presence and availability of enzymes, adult humans and fetuses process ethanol through different pathways.

Gene variation in these enzymes can lead to variation in catalytic efficiency between individuals. The liver is the main organ that metabolizes ethanol due to its high concentration of these enzymes. The food will dilute the alcohol and delay emptying of the stomach into the small intestine where alcohol is absorbed very quickly. According to National Institute on Alcohol Abuse and Alcoholism (NIAAA), it may take two to seven hours for a fasting adult male to return to zero blood alcohol content (BAC) or blood alcohol concentration level after quickly consuming one to four standard drinks. The increase in rate of elimination of alcohol by food was similar for meals of different compositions since there was no difference between carbohydrates, fats and proteins in metabolic rate of alcohol (29-3). Two liver enzymes - alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) - begin breaking down alcohol molecule so that it can eventually be eliminated from body. Most alcohol is oxidized in liver and general principles and general mechanisms of alcohol oxidation will be summarized.

An important pathway for alcohol metabolism involves ADH - an enzyme that catalyzes conversion of alcohol to acetaldehyde. The kinetics of alcohol elimination in vivo and various genetic and environmental factors that can modify rate of alcohol metabolism will be discussed. The absorption of alcohol in duodenum and jejunum is faster than in stomach so rate of gastric emptying is an important determinant of rate of absorption of alcohol administered orally. Alcohol oxidation increases at higher ethanol concentrations and much of this increase is due to alcohol metabolism by CYP2E1. Many P450s are induced by their substrates; this helps remove xenobiotic from body. Women will have higher maximum blood alcohol levels than men when given same dose of alcohol as g per kg body weight but there are no differences when given same dose per liter body water. At low alcohol concentrations CYP2E1 may account for approximately 10% total alcohol oxidation capacity liver. The alcohol dehydrogenase reaction oxidizes alcohol in hepatic cytosol thus producing NADH cytosol. Male relatives male alcoholics are at particularly high risk with expectation becoming alcoholics ranging from 20-50%. U.

S Department Health Human Services National Institutes Health National Institute Alcohol Abuse Alcoholism esters can be detected blood after alcohol no longer detectable therefore detection fatty acid ethyl esters can serve marker alcohol intake. In conclusion, when we consume alcoholic beverages our body processes them through a complex metabolic pathway involving several enzymes such as alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), CYP2E1 etc., which break down ethanol molecule so that it can eventually be eliminated from body.

George Mcnellie
George Mcnellie

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