Prostaglandins

Question 1

What are prostaglandins?

Answer 1

are C-20 fatty acids, based on prostanoic acid

• has a carboxylic acid at the end of one fatty acid chain and a methyl group at the end of the other fatty acid chain
• contains a cyclopentane ring

Question 2

Which molecule forms the starting point for the biosynthesis of prostaglandins?

Answer 2

Z-fatty acid arachidonic acid

- arachidonic acid is derived from linoleic acid (an essential fatty acid)

Question 3

What is the labelling experiment for PGG-2?

Answer 3

looks for the source of oxygen in PGG-2

• When the experiment was conducted in the presence of 18O2 oxygen atoms, all the oxygen atoms at C-9, C-11 and C-15 were all labelled
  = this meant that the oxygen used in the biosynthesis was molecular in origin
• • if a mixture of 16O2 and 18O2 was used, then the isotopes at C-9 and C-11 were always the same
• suggests that the peroxide ring came from the same oxygen molecule

Question 4

What is the enzyme which catalyses the reaction from arachidonic acid to PGG-2?

Answer 4

there are two isozymes of prostaglandin endoperoxide synthase

COX 1 and COX 2 = PGH-2 synthase 1 and 2

Question 5

What is the role of PGH-2 synthase?

Answer 5

introduces the two oxygen molecules at C9, C11 and C15

performs electron reduction of the C15 peroxide to give PGH-2 with a hydroxyl group

Question 6

What is the role of aspirin?

Answer 6

both variants of COX become covalently modified via bond formation with aspirin

• aspirin makes COX inactive by transferring the acyl group to it
  = this is the anti-inflammatory action

Question 7

Why is the selective inhibition of COX-2 a desirable drug target?

Answer 7

COX-1 is needed for normal homeostasis whereas COX-2 is associated with inflammation.