Chapter 68: Ethanol Metabolism

Question 1

Functional definition of alcoholism

Answer 1

• Consumption of alcohol to the point where normal social, sexual or vocational functioning is significantly impaired
• Usually 50% of caloric intake is in the form of alcohol

Question 2

Quantitative definition of alcoholism (WHO)

Answer 2

• Daily consumption of more than 120 grams (4.2 oz.) of pure alcohol per day

Question 3

Ethanol absorption

Answer 3

• Rapidly and without modification

- 20% stomach, 80% in intestines

Question 4

Blood alcohol content

Answer 4

• Detectable within five minutes of consumption

- Peaks in 30 to 45 minutes

Question 5

Blood alcohol concentration curve

Answer 5

• Estimates time needed to absorb and metabolize alcohol

Question 6

After absorption alcohol is distributed to the tissues of the body

Answer 6

• Direct proportion to blood flow
• Small amount not metabolized (excreted via sweat, saliva, urine, breath)
• None is stored

Question 7

BAC vs. time

Answer 7

• 100 mg/dL = legal intoxication

- 50 mg/dL = driving impaired

Question 8

Alcohol metabolism rates

Answer 8

• Metabolized slower than absorbed

- Accumulation = intoxication

Question 9

Oxidative breakdown of alcohol

Answer 9

• Occurs in liver

- Broken down to acetaldehyde (via ADh) –> acetate + acetyl CoA –> CO2 + H2O (via the CAC)

Question 10

Ethanol (alcohol) is metabolized by

Answer 10

• Catalase
• Cytochrome P450
• Alcohol dehydrogenase

Question 11

First pass metabolism of alcohol is reduced by

Answer 11

• Aspirin
• Cimetidine
• Ranitidine

Question 12

Ethanol metabolism generates

Answer 12

• NADH

- Inhibits gluconeogenesis + FA metabolism

Question 13

Gluconeogenic/FA metabolism enzymes inhibited by NADH from ethanol metabolism

Answer 13

• Pyruvate carboxylase

- Malate dehydrogenase

Question 14

NADH produced from the oxidation of ethanol can be used to

Answer 14

• Generate ATP
• Fat deposits observed in the liver (even after one night)
• Liver develops a decreased capacity to burn fat

Question 15

Excess NADH shifts the equilibrium of

Answer 15

• Lactate dehydrogenase reaction

- Accumulation of lactate predisposes to gout

Question 16

Minor pathway of alcohol metabolism

Answer 16

• Isoenzymes of microsomal enzyme cytochrome P 450 (CYP2EI)

Question 17

Isoenzymes of cytochrome P 450 (CYP2EI)

Answer 17

• May be increased after chronic drinking

- Important in accelerated ethanol metabolism (associated with tolerance)

Question 18

Small quantity of alcohol that remains unmetabolized permits

Answer 18

• Measurement of alcohol concentration in breath and urine

Question 19

Food influences alcohol

Answer 19

• More dietary fat = longer absorption

Question 20

Age influences alcohol

Answer 20

• Older = less body water, loss of muscle tissue, decreased metabolism

Question 21

Gender influences alcohol

Answer 21

• Women = higher BACs
• Less body water (and higher body fat) = concentrates alcohol
• Lower activity of gastric/liver alcohol dehydrogenase

Question 22

Body weight influences alcohol

Answer 22

• Doesn’t always result in increased body weight (despite 7.1 kcal/g high caloric value)

Question 23

Medication influences alcohol

Answer 23

• Chronic heavy drinking = activates cytochrome P450

- Acetaminophen pain relievers (e.g Tylenol) can increase risk of kidney/liver disease

Question 24

Short term alcohol related damage

Answer 24

• Inhibition of microsomal hydroxylase system
• CNS effects (sociability & elation)
• Hepatic effects (fat deposition/steatosis, necrosis
• Mitochondrial swelling

Question 25

Long term alcohol related damage

Answer 25

- Induction of cytochrome P450 system - Excess NADH production and NAD utilization - Alcoholic hepatitis (acute or chronic; may be reversible) - Increases susceptibility of liver to other drugs

Question 26

Long term effects of excess NADH production and NAD utilization

Answer 26

- Inhibition of gluconeogenesis | - Alcohol-induced hypoglycemia

Question 27

Alcohol decreases synthesis of liver proteins, causing

Answer 27

- Extended prothrombin time (blood thinning)

Question 28

Alcohol decreases hepatic activation of

Answer 28

- Vitamins

Question 29

Acetaldehyde effects due to alcohol consumption

Answer 29

- Carcinogenic | - Released into the blood, so effects are widespread

Question 30

Chronic alcoholism in men can cause

Answer 30

- Gynecomastia | - Hypotrophy of testes

Question 31

Cirrhosis

Answer 31

- Replacement of liver tissue with fibrous tissue - Causes irreversible loss of liver function - 10-15% of alcoholics have cirrhosis at time of death

Question 32

Production of cirrhosis

Answer 32

- Takes 5-25 years of heavy drinking | - Recall that AST/ALT ratio > 2 in alcoholic liver disease

Question 33

Cirrhosis symptom development

Answer 33

- About 60% of liver tissue can be destroyed before symptoms appear

Question 34

Common symptoms of cirrhosis

Answer 34

- Jaundice - Ascites - Edema

Question 35

Portal hypertension as a result of cirrhosis

Answer 35

- Due to fibrotic build up, blood flow through the liver is impeded - Causes formation of esophageal varices

Question 36

Portal hypertension may be worsened by

Answer 36

- Inadequate prothrombin production by the liver | - Contributes to bleeding esophageal varices common in alcoholics

Question 37

"Advantages" of light alcohol ingestion

Answer 37

- Potential reduced incidence of heart disease - Increasing HDL circulating levels ("good" cholesterol) - Antioxidant effects of various compounds - Antioxidant potential

Question 38

Heme-containing cytochrome P450 2E1 (AKA CYP2E1)

Answer 38

- Also metabolizes ethanol in the liver - Inducible enzyme - Higher Km for ethanol than alcohol dehydrogenase - More significant at increased ethanol consumption