Alcohol Metabolism

Question 1

Where is alcohol metabolised?

Answer 1

LIVER

Question 2

Explain why alcohol metabolism can lead to a decrease in the NAD+/NADH ratio

Answer 2

• Oxidation of alcohol->acetaldehyde and acetaldehyde->acetate both require the reduction of NAD+ to NADH
• This depletes the amount of NAD+ available for liver cells for metabolism

Question 3

What are the effects of a depletion of NAD+ in liver cells?

Answer 3

• Inadequate amounts for b-oxidation of fatty acids
• Needed for the conversion of lactate to pyruvate
• Metabolism of glycerol

Question 4

Describe the consequences of a build up of lactate in the liver and kidneys

Answer 4

• Accumulation in blood can lead to LACTIC ACIDOSIS

- Affects ability of kidney to excrete uric acid -> crystals of urate may accumulate in tissues causing GOUT

Question 5

Explain how excessive alcohol consumption can lead to the patient developing hypoglycaemia

Answer 5

• Decrease in NAD+/NADH ratio
• Less NAD+ available for gluconeogenesis of lactate and glycerol
• If glycogen stores have been depleted, more glucose cannot be synthesised, leading to a decrease in plasma glucose concentration

Question 6

What are the problems associated with increased Acetyl CoA in liver?

Answer 6

• Cannot be oxidised due to decrease in NAD+/NADH ratio
• Increased production of ketone bodies and fatty acids
• High level of ketones can cause KETOACIDOSIS
• Fatty acids can accumulate causing FATTY LIVER

Question 7

Explain how excessive alcohol consumption can cause fatty liver

Answer 7

• Accumulation of acetaldehyde damages liver cells
• Reduced protein synthesis -> insufficient production of lipoproteins
• Lipids synthesised by liver cannot be transported - accumulate leading to fatty liver

Question 8

What are the damaging effects of acetaldehyde on liver cells?

Answer 8

• Leaky plasma membranes -> loss of enzymes such as transaminase and gamma glutamyl transpeptidase
• Reduced capability to conjugate bilirubin -> hyperbilirubinaemia/JAUNDICE
• Reduced protein synthesis of albumin, lipoproteins and clotting factors

Question 9

What are the indirect effects of excessive alcohol consumption?

Answer 9

• Alcoholics generally have poor dietary habits
• Inadequate protein/ carb intake
• Likely to suffer from vitamin and mineral deficiencies

Question 10

What is the direct effect of alcohol on the GI tract?

Answer 10

• Impaired absorption of certain nutrients such as vitamin K, folic acid, pyridoxine and thiamine
• Folic acid deficiencies can cause haematological problems e.g. Anaemia
• Pyridoxine and thiamine deficiencies can cause neurological problems e.g. WERNICKE-KORSAKOFF SYNDROME (mental confusion, unsteady gait)

Question 11

Explain the long term effect of alcohol on the pancreas

Answer 11

• Chronic pancreatitis (inflammation)
• May not cause symptoms until severe pancreatitis develops
• Diabetes -> damage to b-cells in islets that produce insulin so can cause hyperglycaemia and glucosuria

Question 12

Explain how DISULFARIM can be used to treat people who are alcohol dependant

Answer 12

• Inhibits aldehyde dehydrogenase enzyme
• If patients drinks alcohol -> accumulation of acetaldehyde which can cause nausea/symptoms of hangover
• ‘Conditions’ alcohol dependant people to avoid alcohol if they wish to avoid the symptoms

Question 13

What are the 2 main enzymes involved in the oxidation of alcohol?

Answer 13

• Alcohol dehydrogenase
• Aldehyde dehydrogenase
• Small amount can be oxidised by cytochrome P450-2E1 in liver