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Alcohol Metabolism
Jessica Leary
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
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
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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
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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
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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
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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
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Less ADH in females, Native Americans
Less ALDH in Asians
ADH competitive metabolism
ADH pathway disrupts NADH/NAD+ ratio
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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
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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…
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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 calculator
http://rethinkingdrinking.niaaa.nih.gov/toolsresources/calo
riecalculator.asp
Questions?
References
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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/arh294/245255.pdf
Kumar, V., Abbas, A., Fausto, N. Aster, J. (2010). Robbins
and Cotran Pathologic Basis of Disease (8th ed.).
Philidelphia, PA: Saunders Elsevier.