Dangerous byproducts of alcohol breakdown--focus on adducts

Abstract

Alcohol breakdown in the liver results in the generation of the reactive molecule acetaldehyde and, as a byproduct, highly reactive oxygen-containing molecules known as oxygen radicals. Both acetaldehyde and oxygen radicals can interact with proteins and other complex molecules in the cell, forming hybrid compounds called adducts. Other adducts are formed with aldehyde molecules, which are produced through the interaction of oxygen radicals with lipids in the cells. Adduct formation impedes the function of the original proteins participating in the reaction. Moreover, the adducts may induce harmful immune responses. Both of these effects may account for some of the damage observed in alcoholic liver disease. Adduct formation has been shown to occur in the livers of humans and animals consuming alcohol and to start and predominate in those liver regions that show the first signs of liver damage.

Potentially toxic products resulting from the breakdown, or metabolism, of alcohol (chemically known as ethanol). The major alcohol-metabolizing enzymes are alcohol dehydrogenase and cytochrome P450 2E1 (CYP2E1). Alcohol dehydrogenase converts alcohol to acetaldehyde, which can react with other proteins in the cell to generate hybrid molecules known as adducts. CYP2E1 also generates acetaldehyde, as well as highly reactive oxygen-containing molecules called oxygen radicals, including the hydroxyethyl radical (HER) molecule. Elevated levels of oxygen radicals can generate a state of oxidative stress, which through various mechanisms leads to cell damage. Oxygen radicals also can interact with fat molecules (lipids) in the cell in a process known as lipid peroxidation, resulting in reactive molecules such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE). Both of these can react with proteins to form MDA–protein and HNE–protein adducts. MDA also can combine with acetaldehyde and protein to form mixed MDA–acetaldehyde–protein adducts (MAA). HER also interacts with protein to form HER–protein adducts. * Also referred to as “breakdown,” “oxidation,” and “degradation.”