Alcohol Metabolism

Alcohol Metabolism

• The effects of alcohol depend on its concentration in the blood (BAC) over time.
• BAC is determined by the rates of alcohol absorption, distribution, metabolism, and excretion.
• The liver is the primary site of alcohol metabolism.

Enzymes Involved in Alcohol Metabolism

• The two main enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2).
• ADH is present in the liver cytosol and has multiple variants (isozymes).
• ALDH2 is present in the mitochondria.

Metabolism of Ethanol

• Ethanol is metabolized by ADH to produce acetaldehyde, a highly reactive and toxic byproduct.
• Acetaldehyde production can contribute to tissue damage and the addictive process.
• The metabolism of ethanol by ADH requires NAD+, which is reduced by two electrons to form NADH.

Metabolism of Acetaldehyde

• Acetaldehyde is metabolized by ALDH2 to produce acetate.
• The metabolism of acetaldehyde by ALDH2 requires NAD+, which is reduced by two electrons to form NADH.

Extrahepatic Metabolism

• Alcohol can also be metabolized in non-liver tissues, such as the brain, by enzymes like cytochrome P450 and catalase.
• These tissues do not contain ADH.

Pathological Consequences

• Chronic alcohol consumption and metabolism are linked to several pathological consequences and tissue damage.
• Tissue damage can result from the formation of reactive oxygen species (ROS) and changes in the reduction-oxidation (redox) state of liver cells.