Ethanol Metabolism 5/5 (6)

Ethanol Metabolism


Ethanol Metabolism

  • Alcohol is metabolized by several processes or pathways.
  • The most common of these pathways involves two enzymes—alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH).
  • These enzymes help break apart the alcohol molecule, making it possible to eliminate it from the body.
  • First, ADH metabolizes alcohol to acetaldehyde, a highly toxic substance and known carcinogen.
  • Then, in a second step, acetaldehyde is further metabolized down to another, less active byproduct called acetate, which then is broken down into water and carbon dioxide for easy elimination.

Ethanol Metabolism



Location

Cells of the kidney and liver. Greater than 80% of the absorbed ethanol is metabolized in the liver.

  • Substrates: Ethanol, two NAD+.
  • Products: Acetate, two NADH2.

Overview of pathway

  • Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase, in a reaction requiring one NAD+.
  • Acetaldehyde is an unstable compound that is prone to forming free radical structures, and thereby damaging nearby tissues, it is subsequently oxidized to acetate by acetaldehyde dehydrogenase.
  • Again, this reaction requires one NAD+.
  • Acetate can either be excreted in the urine (which occurs in the majority of cases) or can be transformed into acetyl CoA and entered into the citric acid cycle.

The other route of metabolism is through the liver microsomal ethanol oxidizing system (MEOS), which requires a cytochrome P450–containing enzyme.


Important Enzymes

Alcohol dehydrogenase: Requires NAD + and zinc to catalyze the reaction; acts via zero-order kinetics.

Acetaldehyde dehydrogenase: Requires NAD + to function; inhibited by disulfiram, which has been marketed as a drug to treat alcoholism.



Related Diseases

  • Acetaldehyde is an unstable molecule, which is prone to forming free radicals, which can be toxic to the liver (leading to cirrhosis).
  • Acetaldehyde can also be damaging to embryological neural crest tissue and is thought to be involved in the neurologic manifestations of fetal alcohol syndrome.
  • Alcoholics are at risk for hypoglycemia when they ingest ethanol.
  • The increased ratio of NADH/NAD+, which results from the metabolism of ethanol, causes pyruvate and oxaloacetate to be reduced to lactate and malate, respectively.
  • Because pyruvate and oxaloacetate are intermediates in gluconeogenesis, gluconeogenesis is impaired and hypoglycemia can result.

References

  1. David Hames and Nigel Hooper (2005). Biochemistry. Third ed. Taylor & Francis Group: New York.
  2. Smith, C. M., Marks, A. D., Lieberman, M. A., Marks, D. B., & Marks, D. B. (2005). Marks’ basic medical biochemistry: A clinical approach. Philadelphia: Lippincott Williams & Wilkins.
  3. John W. Pelley, Edward F. Goljan (2011). Biochemistry. Third edition. Philadelphia: USA.
  4. https://pubs.niaaa.nih.gov/publications/aa72/aa72.htm

Ethanol Metabolism

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