Metabolic pathways

Question 1

What is the most dominant form of oxidation?

Answer 1

C oxidation

• hydroxylation
• oxidative cleavage

Question 2

What key functional groups would suggest direct phase 2 metabolism?

Answer 2

OH, NH2, COOH

Question 3

What functional groups are vulnerable to reactions?

Answer 3

Esters, nitro, O-methyl, benzene ring etc

Question 4

What reaction are N or O susceptible to?

Answer 4

Oxidative cleavage

Question 5

What is a reactive alpha carbon?

Answer 5

Adjacent to O or N or connected by a double bound

*preferred for oxidations and dealkylations

Question 6

How can metabolites be identified?

Answer 6

• Products excreted in urine (terminal metabolites mainly – formed at the end of the sequence of metabolic pathways) – in vivo
• Products circulating in plasma – in vivo
• Products formed in incubations with liver tissue e.g. liver microsomes – in vitro
• Compete recovery rare so we often have an incomplete picture *(Some metabolites are unstable (can convert back to parent molecule) or non-recoverable)

Question 7

How many sites of oxidation are there for antipyrine?

Answer 7

4:

• phenolic metabolite (oxidation of heterocyclic ring)
• alcoholic metabolite (oxidation of alpha carbon)
• amino metabolite (N-demethylation)
• aromatic OH - unstable, not usually seen

Question 8

GO OVER SPECIFIC MECHANISMS FOR PHASE 1/2 REACTIONS

Answer 8

GO OVER SPECIFIC MECHANISMS FOR PHASE 1/2 REACTIONS

Question 9

What is the OH group on propranolol an indicator of?

Answer 9

Indicator that it can undergo direct conjugation

Question 10

Which carbon position on lignocaine is the most sensitive to aromatic hydroxylation?

Answer 10

Para position

Question 11

what does crossover between metabolic pathways in lignocaine give?

Answer 11

Common end products excreted in urine