USMLE Step 1


Biochemical Pathways

Ethanol Metabolism
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Ethanol Metabolism

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Alcohol or Ethanol Metabolism occurs in the liver through several steps, beginning with ethanol (alcohol), proceeding through acetaldehyde, and ending with acetate (acetic acid), which is excreted in the urine.

First, ethanol can be metabolized into acetaldehyde in 3 ways. The most important way is through alcohol dehydrogenase in the cytoplasm, which is blocked by the drug, fomepizole. Alcohol dehydrogenase operates via zero-order kinetics, which means that it operates at a constant rate regardless of how much alcohol is present (amount ingested). Less important enzymes include CYP2E1 in the microsome, or catalase in the peroxisome.

The acetaldehyde is then metabolized into acetate through the actions of aldehyde dehydrogenase. The drug disulfiram is given to discourage drinking, as it blocks aldehdye dehydrogenase and leads to the build-up of the toxic intermediate: acetaldehyde.

The metabolism of alcohol usually generates 2 molecules of NADH from NAD+, which increases the NADH to NAD+ ratio. The increase in this ratio leads to a number clinical findings, such as lactic acidosis, fasting hypoglycemia, hepatosteatosis, and ketogenesis.

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