Question

Given below are two statements:
Statement I: Suicidal inhibitor causes covalent modification of an enzyme active site and enzyme permanently becomes inactive
Statement II: Covalent modification of enzyme active site is initiated after binding of substrate to the active site of an enzyme - suicidal inhibitor complex
In the light of the above statements, choose the most appropriate answer from the options given below

• A. Both Statement I and Statement II are true
• B. Both Statement I and Statement II are false
• C. Statement I is correct but Statement II is false
• D. Statement I is incorrect but Statement II is true

Hint:

Suicide Inhibition (Mechanism-Based): Enzyme turns the inhibitor into its own irreversible poison (e.g., Allopurinol on Xanthine oxidase, Penicillin on Glycopeptide transpeptidase).

Answer 1

The Correct Option is C

Step 1: Understanding the Concept:
Suicide inhibitors (mechanism-based inactivators) are converted by the enzyme's own catalytic machinery into chemically reactive species that permanently modify the active site.
Key Formula or Approach:
\[ E + I \rightleftharpoons E\cdot I \xrightarrow{k_{\text{cat}}} E\cdot I^* \xrightarrow{\text{Covalent}} E\text{-Inactivated (Irreversible)} \]

Step 2: Detailed Explanation:
1. Statement I: Suicide Inhibitors (Mechanism-based inactivators) are unreactive substrate analogues that bind to the active site, undergo the initial catalytic steps by the enzyme, and generate a highly reactive intermediate ($I^*$) that forms an irreversible covalent bond with active site residues, permanently inactivating the enzyme. Hence, Statement I is correct.
2. Statement II: Covalent inactivation occurs directly during the catalytic turnover of the inhibitor itself, not by the subsequent binding of natural substrate to an enzyme-inhibitor complex. Hence, Statement II is false.

Step 3: Final Answer:
Hence, Statement I is correct but Statement II is false, matching option (C).