Alcohol MetabolismJessica Leary

Ethanol

What is Alcohol?

Ethyl alcohol, or ethanol, is the common alcohol that will make one intoxicated when ingested. This is the chemical this is found in beer, wine, and liquor.

Ethanol Formation

Ethanol is a fermentation (anaerobic) product of yeast.It is a two step process.

Ethanol Formation: Step 1

Pyruvate acetaldehyde by enzyme pyruvate decarboxylase Pyruvate decarboxylase: uses thiamine pyrophosphate (TPP)

• Coenzyme thiamin/B1

By product CO2

Ethanol Formation: Step 2

Acetaldehyde ethanol by alcohol dehydrogenase • Cofactor for alcohol dehydrogenase: Zn2+

Uses NADH + H+

Digestion and Metabolism

• Fully metabolized: 7kcal/g• 20% to 25% enters via the stomach • 75% to 80% enters via the small intestine

Two pathways of metabolism:The Alcohol Dehydrogenase Pathway (ADH)The Microsomal Ethanol Oxidizing System

(MEOS)

ADH Pathway

• Breaks down ethanol to acetate • Alcohol dehydrogenase (ADH) is found in the

cytosol of liver cells• Acetaldehyde dehydrogenase is found in

mitochondria

Microsomal Ethanol Oxidizing System

• At blood concentrations above 100 mg/dL• Attempts to compensate for overflow from

ADH pathway• Occurs in the smooth endoplasmic

reticulum • Utilizes CYP2E1• ROS = reactive oxygen species

Acetate

• Oxidized to carbon dioxide CO2

• Metabolized to CO2 in heart, skeletal muscle, and brain cells.

• Increases blood flow into the liver• Depresses the central nervous system• Also converted to Acetyl CoA

Problems and Considerations

• Less ADH in females, Native Americans• Less ALDH in Asians• ADH competitive metabolism • ADH pathway disrupts NADH/NAD+ ratio

• Needed in TCA, fatty acid oxidation, gluconeogenesis• Fatty liver disease/cirrhosis • Impairs glucose metabolism• Changes lactate production in liver • Reduced oxygen in the liver

Problems and Considerations

• CYP2E1 is responsible for metabolizing other drugs

• CYP2E1 inductable • CYP2E1 increases free radical formation,

accelerates fatty liver disease/cirrhosis • Acetaldehyde interference• Aldehyde induced immune-mediated

hepatotoxicity or antibody-dependent cell-mediated cytotoxicity (ADCC)

But I just got drunk for one night…

• Sense of euphoria, lack of inhibition, delayed reaction time• Dopamine, GABA, Glutathione

• Effects cerebral cortex, cerebellum, medulla, hypothalamus and pituitary gland

• Lack of circulating glucose makes you crave carbs

• Acetaldehyde makes us feel sick• Effects mineral concentration

Fun Facts:

Calorie calculatorhttp://rethinkingdrinking.niaaa.nih.gov/toolsresources/caloriecalculator.asp

Questions?

References

• Boyer, R. (2006). Concepts in Biochemistry (3rd ed.). Hoboken, NJ: John Wiley & Sons, Inc.

• Gropper, S.S., Smith, J.L. (2013). Advanced Nutrition and Human Metabolism (6th ed.). Belmont, CA: Wadsworth.

• Zakhari, S. (2006). Overview: How Is Alcohol • Metabolized by the Body? Retrieved from: http://

pubs.niaaa.nih.gov/publications/arh294/245-255.pdf

• Kumar, V., Abbas, A., Fausto, N. Aster, J. (2010). Robbins and Cotran Pathologic Basis of Disease (8th ed.). Philidelphia, PA: Saunders Elsevier.