Lecture 3.1a - Alcohol Metabolism and oxidative stress

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Questions and Answers

What is the main reason why women generally have a higher blood alcohol concentration than men?

Women have a lower volume of distribution for alcohol due to their higher body fat percentage. (correct)

Women have a lower concentration of alcohol dehydrogenase in the liver.

Women have a faster rate of alcohol absorption in the stomach and intestine.

Women have a higher percentage of body fat.

What is the primary mechanism by which ethanol crosses biological membranes?

Simple passive diffusion (correct)

Facilitated diffusion requiring transporters

Osmosis through water channels

Active transport requiring energy

What is the primary organ responsible for metabolizing alcohol?

Brain

Skeletal muscle

Liver (correct)

Kidneys

What is the toxic metabolite of ethanol?

Acetaldehyde Signup and view all the answers

What happens to the absorption of alcohol when food is present in the stomach?

The absorption of alcohol is decreased. Signup and view all the answers

What is the approximate percentage of water in a woman's body?

45-50% Signup and view all the answers

What is the effect of ingesting ethanol as a single dose compared to several smaller doses?

Peak blood alcohol levels are higher with a single dose. Signup and view all the answers

What happens to the remainder of unmetabolized ethanol in the body?

It is excreted in the urine and on breath. Signup and view all the answers

What percentage of ingested ethanol is oxidized through cytochrome P450 enzymes in the endoplasmic reticulum?

10-20% Signup and view all the answers

What is the effect of higher concentrations of ethanol on the affinity of CYP2E1?

It increases the affinity of CYP2E1 Signup and view all the answers

What is the main consequence of chronic ethanol abuse in the liver?

Alcohol-induced liver disease Signup and view all the answers

What is the main mechanism of liver damage in fatty liver?

Inhibition of fatty acid oxidation and stimulation of triacylglycerol synthesis Signup and view all the answers

What is the mechanism of action of Disulfiram in treating alcohol use disorder?

It inhibits aldehyde dehydrogenase Signup and view all the answers

What is the result of Disulfiram blocking the oxidation of alcohol at the acetaldehyde stage?

The accumulation of acetaldehyde in the blood Signup and view all the answers

What is the consequence of chronic ethanol consumption on fatty acid metabolism?

Inhibition of fatty acid oxidation Signup and view all the answers

What is the characteristic of liver damage in alcoholic cirrhosis?

Damage to hepatocytes characterized by fibrosis Signup and view all the answers

Study Notes

Ethanol Characteristics

Ethanol is a small molecule that is both lipid and water soluble, but practically insoluble in fats and oils.
It is transported by simple diffusion across the cell membrane.

Distribution of Ethanol in the Body

Ethanol distributes from the blood into all tissues and fluids in proportion to their relative water content.
Women have a smaller volume of distribution for alcohol than men due to their higher percentage of body fat.
The equilibrium concentration of alcohol in a tissue depends on the relative water content, rate of blood flow, and the mass of that tissue.
A woman's body is composed of approximately 45-50% water, while a man's body is about 55-65% water.
The lower fluid volume in women results in higher concentrations of alcohol in the bloodstream compared to men.

Alcohol Absorption

Alcohol is absorbed in the stomach and intestine tissues.
It crosses biological membranes by simple passive diffusion, not requiring transporters or energy.
Peak blood alcohol levels are higher if ethanol is ingested as a single dose rather than several smaller doses.
The presence of food in the stomach retards gastric emptying, reducing the absorption of alcohol.

Alcohol Metabolism

Most (>90%) alcohol is metabolized by the liver.
The remainder is excreted passively in urine and on breath (10%).
Enzymes involved in metabolism include alcohol dehydrogenase (ADH) and cytochrome P450.
Acetaldehyde is toxic and is metabolized further by acetaldehyde dehydrogenases (ALDH) into acetate.
Acetate is not toxic and is converted to acetyl-CoA in the skeletal muscle.
Approximately 10-20% of ingested ethanol is oxidized through cytochrome P450 enzymes in the endoplasmic reticulum (especially CYP2E1).
CYP2E1 has the highest activity toward ethanol and is inducible.

Liver Damage

Alcohol-induced liver disease is a common and sometimes fatal consequence of chronic ethanol abuse.
Forms of liver damage include fatty liver, alcohol-induced hepatitis, and alcoholic cirrhosis.
Many toxic effects of chronic ethanol consumption result from accumulation of acetaldehyde.
Changes in fatty acid metabolism, generation of free radicals, and chronic loss of function contribute to liver damage.

Clinical Presentation of Liver Damage

Mechanisms of liver damage include:
- Fatty liver: inhibition of fatty acid oxidation and stimulation of triacylglycerol synthesis, leading to more fat produced.
- Alcoholic hepatitis: generation of free radicals from acetaldehyde.
- Alcoholic cirrhosis: damage to hepatocytes characterized by fibrosis, abnormal blood flow, and loss of liver function.

Treatment of Alcohol Dependence

Disulfiram is a drug used to support the treatment of alcohol use disorder.
It inhibits aldehyde dehydrogenase, resulting in the accumulation of acetaldehyde (toxic).
Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage.
Accumulation of acetaldehyde in the blood produces a complex of highly unpleasant symptoms (hangover).

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Description

Learn about the properties and distribution of ethanol in the human body, including its solubility, transport, and effect on body composition.