Discuss the 3 pathways of ethanol metabolism.

Expert Solution

The process of ethanol metabolism involves three distinct enzymatic pathways.

The most significant pathway, responsible for the bulk of ethanol metabolism, is that initiated by alcohol dehydrogenase, ADH in the stomach. Humans express several ADH genes with the class I members being responsible for hepatic ethanol metabolism. The ADH enzymes are NAD+-requiring and they are expressed at high concentrations in hepatocytes. Animal cells (primarily hepatocytes) contain cytosolic ADH which oxidizes ethanol to acetaldehyde. Acetaldehyde then enters the mitochondria where it is oxidized to acetate by mitochondrial aldehyde dehydrogenase (ALDH). A cytosolic ALDH exists but is responsible for only a minor amount of acetaldehyde oxidation.

The second major pathway for ethanol metabolism is the microsomal ethanol oxidizing system (MEOS) which involves the cytochrome P450 enzyme CYP2E1 and requires NADPH instead of NAD+ as for ADH. The MEOS pathway is induced in individuals who chronically consume alcohol.

The third pathway involves a non-oxidative pathway catalyzed by fatty acid ethyl ester (FAEE) synthase. This latter pathway results in the formation of fatty acid ethyl esters and takes place primarily in the liver and pancreas, both of which are highly susceptible to the toxic effects of alcohol.

Oxidation of ethanol can also occur in peroxisomes via the activity of catalase. However, this oxidation pathway requires the presence of a hydrogen peroxide (H2O2) generating system and as such plays no major role in alcohol metabolism under normal physiological conditions.

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gladiator answered 2 years ago

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