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AAT Bioquest

What are the steps involved in ethanol metabolism?

Posted February 22, 2024


Answer

When ethanol is present at low concentrations, its oxidation occurs through a two-step process involving both the cytosol and the mitochondria. The first step, facilitated by alcohol dehydrogenase (ADH), takes place in the cytosol and results in the production of acetaldehyde. Acetaldehyde, as a result, is converted into acetate within the mitochondria by the enzyme acetaldehyde dehydrogenase (ALDH). This acetate is then transported in the bloodstream and can serve as an energy source for peripheral tissues. The next step involves the conversion of acetate into acetyl-CoA via acetyl-CoA synthetase. Lastly, acetyl-CoA enters the tricarboxylic acid (TCA) cycle for oxidation. Throughout these processes, each step in the oxidation of ethanol generates NADH, contributing to an increased ratio of NADH to NAD+ in the cell. 

When ethanol concentrations are increased, the microsomal ethanol oxidizing system (MEOS) becomes activated as well as the proliferation of the smooth endoplasmic reticulum in the liver. Chronic alcohol consumption results in increased expression of the P450 enzyme CYP2E1, a key component of MEOS. γ-Glutamyltransferase (GGT), an enzyme located in the smooth endoplasmic reticulum, is also upregulated. Unlike the oxidation of ethanol at lower concentrations, the MEOS pathway at higher alcohol intake does not substantially affect the NADH/NAD+ ratio.

Additional resources

Overview: How Is Alcohol Metabolized by the Body?

Cell Metabolism

Amplite® Ethanol Quantitation Kit