Alcohol metabolism in the human body
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Alcohol Absorption and Distribution in the Human Body
Alcohol (ethanol) is absorbed rapidly and efficiently throughout the digestive tract, with about 20% absorbed from the stomach and 80% from the small intestine. The rate of absorption depends on factors such as the type and concentration of the alcoholic beverage, the presence of food in the stomach, and individual physiological differences. Once absorbed, alcohol is quickly distributed throughout the body’s water compartments, and its concentration in body fluids is determined by their water content. The maximum blood alcohol concentration is typically reached within 10 to 60 minutes after consumption, depending on these factors 16.
Main Pathways of Alcohol Metabolism: Liver Enzymes and Mechanisms
The liver is the primary site for alcohol metabolism, although other tissues like the kidney, muscle, lung, and intestine play minor roles. Over 90% of absorbed alcohol is metabolized, with the remainder excreted unchanged in urine, breath, and sweat 16. The main metabolic pathway involves the enzyme alcohol dehydrogenase (ADH), which converts ethanol to acetaldehyde in the liver cytoplasm. This reaction uses nicotinamide adenine dinucleotide (NAD+) as a cofactor. Acetaldehyde is then further metabolized to acetate by aldehyde dehydrogenase (ALDH) 125710.
Other enzymes, such as cytochrome P450 (specifically CYP2E1, also known as the microsomal ethanol oxidizing system or MEOS) and catalase, also contribute to ethanol metabolism, especially at higher alcohol concentrations or in chronic drinkers. These alternative pathways can generate reactive oxygen species (ROS), which may contribute to tissue damage 2810.
Genetic and Individual Variations in Alcohol Metabolism
There are significant genetic differences in the activity of ADH and ALDH enzymes, which affect how quickly individuals metabolize alcohol and their susceptibility to alcohol-related health issues. Different isozymes and allozymes of ADH and ALDH are present in the liver and gastrointestinal tract, and their distribution and activity can vary by ethnicity and genotype. For example, certain ADH1B and ADH1C variants are more efficient at metabolizing ethanol, leading to faster clearance rates in some individuals 57.
Kinetics and Elimination of Alcohol
Alcohol metabolism follows dose-dependent kinetics. At low to moderate concentrations, the ADH enzyme becomes saturated, and elimination follows zero-order kinetics, meaning alcohol is cleared from the body at a constant rate, typically 10–35 mg% per hour for moderate drinkers. Only a small fraction of alcohol undergoes non-oxidative metabolism, forming compounds like ethyl glucuronide and ethyl sulfate, which are excreted in urine .
Metabolic and Physiological Effects of Alcohol Metabolism
The process of metabolizing alcohol alters the body’s redox state by increasing the NADH/NAD+ ratio in liver cells. This shift affects many metabolic pathways, including fatty acid oxidation, gluconeogenesis, and carbohydrate metabolism, and can lead to the accumulation of fatty acids and other metabolic disturbances. Byproducts of alcohol metabolism, such as acetaldehyde and ROS, can cause tissue damage, contribute to liver disease, and interact with medications and other substances 2810.
Conclusion
Alcohol metabolism in the human body is a complex process primarily carried out by the liver through the action of ADH and ALDH enzymes, with contributions from CYP2E1 and catalase. Genetic differences, physiological factors, and drinking patterns all influence the rate and consequences of alcohol metabolism. The metabolic byproducts and changes in cellular redox state can have significant health effects, especially with chronic or excessive alcohol consumption 12567810.
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