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

Answer 1

The Correct Option is D

The correct option is (D): Methyl group.

Answer 2

The question asks which functional group on a drug molecule is most likely to be attacked by cytochrome P450 enzymes during phase I oxidative metabolism. Let's look at how each group is normally handled by the body.

1. Ester group: Ester groups are usually broken apart by esterase enzymes through hydrolysis, splitting the molecule into an acid and an alcohol. That is a hydrolysis reaction, a different phase I pathway from CYP450 oxidation.
2. Amide group: Amide groups are similarly cleaved by amidase enzymes through hydrolysis rather than oxidation, so they are not the typical substrate for CYP450 attack either.
3. Hydroxyl group: A hydroxyl group is already an oxidized, polar site on the molecule. Rather than being oxidized further by CYP450, it is usually the point where phase II enzymes attach a sugar or sulfate group, so it is more linked to conjugation than to oxidation.
4. Methyl group: A methyl group is a small, nonpolar, unfunctionalized carbon chain, exactly the kind of site CYP450 monooxygenases are built to attack. They insert an oxygen to convert it into a hydroxymethyl group, or remove it entirely through O- or N-demethylation, both classic CYP450 oxidation reactions.

Since CYP450 oxidation works by adding oxygen to unfunctionalized carbons, a methyl group is the most likely site of attack among the options given.

Therefore, the correct answer is Methyl group.