Overview: how is alcohol metabolized by the body?
Alcohol is eliminated from the body by various metabolic mechanisms. The primary enzymes involved are aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 (CYP2E1), and catalase. Variations in the genes for these enzymes have been found to influence alcohol consumption, alcohol-related tissue damage, and alcohol dependence. The consequences of alcohol metabolism include oxygen deficits (i.e., hypoxia) in the liver; interaction between alcohol metabolism byproducts and other cell components, resulting in the formation of harmful compounds (i.e., adducts); formation of highly reactive oxygen-containing molecules (i.e., reactive oxygen species [ROS]) that can damage other cell components; changes in the ratio of NADH to NAD+ (i.e., the cell's redox state); tissue damage; fetal damage; impairment of other metabolic processes; cancer; and medication interactions. Several issues related to alcohol metabolism require further research. KEY WORDS: Ethanol-to-acetaldehyde metabolism; alcohol dehydrogenase (ADH); aldehyde dehydrogenase (ALDH); acetaldehyde; acetate; cytochrome P450 2E1 (CYP2E1); catalase; reactive oxygen species (ROS); blood alcohol concentration (BAC); liver; stomach; brain; fetal alcohol effects; genetics and heredity; ethnic group; hypoxia
The effects of alcohol (i.e., ethanol) on various tissues depend on its concentration in the blood (blood alcohol concentration [BAC]) over time. BAC is determined by how quickly alcohol is absorbed, distributed, metabolized, and excreted. After alcohol is swallowed, it is absorbed primarily from the small intestine into the veins that collect blood from the stomach and bowels 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. The rate of the rise of BAC is influenced by how quickly alcohol is emptied from the stomach and the extent of metabolism during this first pass through the stomach and liver (i.e., first-pass metabolism [FPM]).
BAC is influenced by environmental factors (such as the rate of alcohol drinking, the presence of food in the stomach, and the type of alcoholic beverage) and genetic factors (variations in the principal alcohol-metabolizing enzymes alcohol dehydrogenase [ADH] and aldehyde dehydrogenase [ALDH2]). The alcohol elimination rate varies widely (i.e., three-fold) among individuals and is influenced by factors such as chronic alcohol consumption, diet, age, smoking, and time of day (Bennion and Li 1976; Kopun and Propping 1977).
The consequent deleterious effects caused by equivalent amounts of alcohol also vary among individuals. Even after moderate alcohol consumption, BAC can be considerable (0.046 to 0.092 gram-percent [g%]; in the 10- to 20-millimolar (1) [mM] range). Alcohol readily diffuses across membranes and distributes through all cells and tissues, and at these concentrations, it can acutely affect cell function by interacting with certain proteins and cell membranes. As explained in this article, alcohol metabolism also results in the generation of acetaldehyde, a highly reactive and toxic byproduct that may contribute to tissue damage, the formation of damaging molecules known as reactive oxygen species (ROS), and a change in the reduction-oxidation (or redox) state of liver cells. Chronic alcohol consumption and alcohol metabolism are strongly linked to several pathological consequences and tissue damage.
Understanding the balance of alcohol's removal...