Question

Which of the following phase I enzymes has major contribution in drug metabolism?
A. CYP2A6
B. CYP2D6
C. CYP3A4
D. CYP2D9
E. CYP3A9
Choose the correct answer from the options given below:

• A. A and B only
• B. D and E only
• C. C only
• D. E only

Hint:

Drug Metabolism Statistics:
CYP3A4 is the #1 Phase I metabolic enzyme, biotransforming $> 50\%$ of all clinical drugs. CYP2D6 metabolizes $\approx 20-25\%$.

Answer 1

The Correct Option is C

Step 1: Understanding the Concept:
Hepatic cytochrome P450 monooxygenase superfamily: the CYP3A4 isoform is the most abundantly expressed hepatic isozyme responsible for metabolizing > 50% of all therapeutic drugs.
Key Formula or Approach:
\[ \text{CYP3A4} = 30\% \text{ of Total Hepatic P450 Pool} \implies \text{Metabolizes } > 50\% \text{ of All Clinically Used Drugs} \]

Step 2: Detailed Explanation:
In xenobiotic biotransformation and Phase I drug metabolism:
- The Cytochrome P450 (CYP450) superfamily catalyzes Phase I oxidative, reductive, and hydrolytic functionalization reactions.
- Among all known mammalian CYP isozymes, CYP3A4 (and its veterinary orthologs like canine CYP3A12/CYP3A26):
1. Constitutes $\approx 30\%$ of total cytochrome P450 protein content in the liver and small intestinal enterocytes.
2. Possesses a remarkably large, flexible substrate-binding pocket.
3. Accounts for the metabolism of over 50% of all therapeutic pharmaceuticals in clinical veterinary and human medicine.
Thus, CYP3A4 (C only) makes the single greatest major contribution.

Step 3: Final Answer:
Thus, the enzyme with major contribution is C only, matching option (C).