3. Alcohol metabolism

Question 1

What is the energy content of alcohol?

Answer 1

High: 29 kJ/g

Question 2

What is the recommended limit for alcohol intake?

Answer 2

14 units/week spread over at least 3 days for both men and women

Question 3

How is alcohol eliminated by the body? At what rate does this occur?

Answer 3

> 90% metabolised by liver
< 10% excreted passively in urine and on breath
eliminated at rate of 7g/hr

Question 4

Explain how alcohol is converted for energy production? Which enzymes are involved?

Answer 4

• Most alcohol is oxidised in liver by alcohol dehrdogenase to acetaldehyde and then to acetate by aldehyde dehydrogenase.
• Acetate conjugated to coenzyme A to form acetyl~CoA and used in TCA cycle or for fatty acid synthesis.
• Smaller amounts of alcohol can also be oxidised by cytochrome P450 enzyme (CYP2E1) or by catalase in brain.

Question 5

What is the toxic component of alcohol?

Answer 5

Acetaldehyde (extremely toxic to cells)

Question 6

How is acetaldehyde toxicity usually kept to a minimum?

Answer 6

Aldehyde dehydrogenase has a very low Km for acetaldehyde - removes it as soon as it is formed.

Question 7

Give 3 reasons why alcohol overconsumption has negative health effects.

Answer 7

1. toxic effects of aldehyde accumulation causes liver damage
2. increased levels of NADH in liver because of alcohol oxidation… decrease in NAD+/NADH ratio - affects metabolism
3. increased availability of acetyl~CoA (as a result of alcohol catabolism) - affects metabolism

Question 8

Explain the effects of a decrease in NAD+:NADH on liver cell metabolism.

Answer 8

1. Inadequate NAD+ for conversion of lactate to pyruvate… lactate accumulation in blood…
   a) lactic acidosis
   b) reduced kidney ability to excrete uric acid… urate crystals accumulate in tissues… gout
2. Inadequate NAD+ for glycerol metabolism… combined liver cell inability to use lactate and glycerol… gluconeogenesis cannot be activated… fasting hypoglycaemia
3. Inadequate NAD+ for fatty acid oxidation… contributes to fatty liver.

Question 9

Explain the effects of increased availability of acetyl~CoA on the liver.

Answer 9

Increased availability of acetyl~CoA to liver cells combined with inadequate NAD+ for fatty acid oxidation … increased synthesis of fatty acids and ketone bodies…

a) conversion of fatty acids to triaglycerols… cannot be transported from liver due to lower lipoprotein synthesis (from direct damage to liver by acetaldehyde)… fatty liver.
b) in some cases, ketone body production causes ketoacidosis.

Question 10

Explain and give examples of the effects of liver cell damage caused by acetaldehyde.

Answer 10

Damaged liver cells have leaky plasma membranes… loss of enzymes (transaminases and y-glutamyl transpeptidase) from cells. Cells cannot adequately perform functions, e.g.

• reduced capacity to take up and conjugate bilirubin… hyperbilirubinaemia… jaundice.
• reduced capacity to produce urea… hyperammonaemia… increased [glutamine].
• reduced protein synthesis…
  a) decreased levels of albumin… oedema.
  b) decreased levels of clotting factors… increase in blood clotting time.
  c) decreased levels of lipoproteins… lipids synthesised in liver cannot be transported from liver… fatty liver.

Question 11

Why can alcohol over-consumption lead to vitamin/nutrient deficiencies?

Answer 11

1. Associated with poor dietary habit due to cost of alcohol and effects on CNS.
2. High [alcohol] damage lining of GI tract… variety of GI tract disturbances: loss of appetite, diarrhoea, impaired absorption of certain nutrients such as vitamin K, folic acid, pyridoxine and thiamine.
   - Symptoms of specific vitamin deficiencies often seen in alcoholics.
   - Neurological symptoms associated with thiamine/pyridoxine deficiencies and haematological problems (eg anaemia) associated with folic acid deficiency common in alcoholics.
   - Thiamine deficiency can lead to Wernicke-Korsakoff syndrome with mental confusion and unsteady gait.

Question 12

How can chronic heavy alcohol consumption affect the pancreas? What are the associated symptoms?

Answer 12

1. Chronic pancreatitis
   
   • chronic pain in upper abdomen that radiates to back
   • weight loss from malabsorption of food due to insufficient production of pancreatic enzymes
2. Diabetes (if insulin-producing pancreatic beta cells are damaged)
   
   • hyperglycaemia
   • glucosuria

Question 13

What is Disulfiram used for and what is its MOA?

Answer 13

• Adjunct in treatment of chronic alcohol dependence.
• Inhibitor of aldehyde dehydrogenase so if alcohol is consumed, acetaldehyde accumulates in blood and causes symptoms of hangover (eg nausea).