Tutorial: Drug Metabolism

Question 1

Where are the Cytochrome P450 enzymes located?

Answer 1

Primarily in the Smooth ER (in liver but also in other tissues)

Question 2

Which factors does Oxitation reaction in Phase 1 metabolism require?

Answer 2

Requires

• NADPH (as co-enzyme)
• often molecular oxygen

Question 3

Glutathione is a tripeptide consisting of:

Answer 3

• Glycin
• Cystein (with thiol group)
• Glutamic acid

Question 4

What is the enzyme and co-substrate needed for Sulphation reaction?

Answer 4

Sulphation

• sulphotransferase
• 3’phosphoadenosyl-5’-phosphosulphate (PAPS)

Question 5

Which enzyme and co-substrate are needed for Glucoronidation?

Answer 5

Glucoronidation

• Enzyme: UDP-glucuronosyltransferase
• Co-substrate: UDP-glucuronic acid (UDP-GA)

Question 6

Which Enzyme and Co-enzyme is needed for Glutathione conjugation reactions?

Answer 6

Glutathiodine conjugation

• for electrophilic substraties (often produced by phase I oxidation)
• Co-substrate: Glutathione
• Enzyme needed: Glutathione-S-transferase

Question 7

Which Phase 2 Metabolism reactions does Paracetamol undergo?

Answer 7

1. 40-60% sulfation
2. 20-30% glucoronidation
3. 10% Glutathione conjugation –> neutralisation of NAPQI

Question 8

How could you treat a Paracetamol overdose?

Answer 8

Oral/I.V. N-acetylcysteine

• promote synthesis of GSH (Glutathione)
• more capacity for metabolism of Paracetamol
• needed for conjugation of NAPQI and for protection of protein thiols