Chapter 3 Answers to self check questions

1  There is one chiral carbon atom in warfarin – it is marked with a red star in the first structure. The priority of the groups is shown below; remember to reverse the assignment when the priority 4 group (H, in this case) is at the front on the solid wedge bond.

2  Substrates for an enzyme tend to ‘fit’ neatly into the active site. Non-bonding interactions – such as hydrogen bonds and lipophilic interactions – ‘hold’ the substrate within the active site of the enzyme. The 3-dimensional structures of the two enantiomers are different and they fit preferentially into the active sites of different enzymes.

3  If a patient produces more CYP 2C9 than usual, the (S)-warfarin enantiomer is metabolised quickly and they have less (S)-warfarin in the blood to exert an anticoagulant effect than someone who metabolises it slowly. On the other hand, if a patient produces an inactive form of CYP 2C9, the (S)-warfarin is metabolised more slowly. If the dose of warfarin is not reduced to account for this, the patient could have a haemorrhage. This is why monitoring the effects of warfarin by checking a patient’s internationalised normalised ratio (INR) is so very important.