Question

Fluoroacetate inhibit the action of enzyme

• A. Aconitase
• B. Citrate synthase
• C. Isocitrate dehydrogenase
• D. Alpha-ketoglutarate dehydrogenase

Hint:

Lethal Synthesis: Fluoroacetate $\rightarrow$ Fluorocitrate $\rightarrow$ Potent suicide inhibitor of ACONITASE in TCA cycle.

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
Mechanism-based suicide inhibition (lethal synthesis) converts a pro-toxin into a competitive transition-state inhibitor of a downstream metabolic enzyme.
Key Formula or Approach:
\[ \text{Fluoroacetate} + \text{CoA} + \text{Oxaloacetate} \xrightarrow{\text{Citrate Synthase}} \text{Fluorocitrate} \xrightarrow{\text{Inhibits}} \text{Aconitase (Blocked)} \]

Step 2: Detailed Explanation:
Fluoroacetate is a classic suicide substrate:
1. Inside the cell, fluoroacetate is converted into fluoroacetyl-CoA, which condenses with oxaloacetate via citrate synthase to produce (2R,3S)-fluorocitrate (a process known as 'lethal synthesis').
2. Fluorocitrate binds tightly to the active site [4Fe-4S] cluster of Aconitase (Aconitate hydratase), irreversibly blocking the isomerization of citrate to isocitrate and halting the Tricarboxylic Acid (TCA) cycle.

Step 3: Final Answer:
Thus, fluoroacetate inhibits the enzyme Aconitase, corresponding to option (A).