Question

Which functional group in drug molecules is most likely to undergo phase I metabolic oxidation by cytochrome P450 enzymes:

• A. Ester group
• B. Amide group
• C. Hydroxyl group
• D. Methyl group

Hint:

In phase I metabolism, cytochrome P450 enzymes primarily oxidize methyl groups, introducing hydroxyl groups to enhance drug polarity for excretion.

Answer 1

The Correct Option is D

Step 1: Role of cytochrome P450 enzymes in phase I metabolism. Cytochrome P450 enzymes are responsible for oxidative reactions in phase I metabolism. These reactions increase the polarity of drug molecules, preparing them for subsequent phase II metabolism and excretion. 

Step 2: Oxidation of functional groups. Among the given functional groups: 
- The methyl group is most likely to undergo oxidation, often forming hydroxyl groups (-CH₃ → -CH₂OH). This process is common in drugs containing alkyl groups. 
- Other functional groups like esters and amides are usually hydrolyzed rather than oxidized. 
- Hydroxyl groups are already oxidized and typically undergo conjugation in phase II metabolism rather than phase I oxidation. 

Step 3: Incorrect options. 
- (A) Ester group: Hydrolyzed in phase I metabolism, not oxidized. 
- (B) Amide group: Hydrolyzed or remains intact during phase I metabolism. 
- (C) Hydroxyl group: Generally conjugated in phase II metabolism, not oxidized.