Question

A cell suspension of actively respiring mitochondria is treated with either chemical X (experiment 1) or chemical Y (experiment 2), or left untreated (experiment 3).
Chemical X selectively inhibits electron transport from Complex I to ubiquinone, while chemical Y selectively inhibits electron transport from Complex III to cytochrome C.
Which one of the following options represents the correct order of relative number of ATP synthesised in mitochondria?

• A. Experiment 2 $<$ Experiment 1 $<$ Experiment 3
• B. Experiment 1 $<$ Experiment 2 $<$ Experiment 3
• C. Experiment 1 = Experiment 2 = Experiment 3
• D. Experiment 2 $<$ Experiment 1 = Experiment 3

Hint:

An inhibitor that blocks a downstream bottleneck (like Complex III or IV) is always more disruptive than one that blocks only one of the upstream entry ports (like Complex I), because the other entry port (Complex II) can partially compensate.

Answer 1

The Correct Option is A

Step 1 : Understanding the Question:
This question asks us to compare the relative amounts of ATP produced in three different experiments based on the effects of two metabolic inhibitors on the electron transport chain (ETC) in mitochondria.

Step 2 : Key Formulas and Approach:
The approach involves tracing the pathway of electron flow from electron donors (NADH and $FADH_2$) through the different complexes of the ETC to oxygen, and determining how blocking specific steps impacts the proton gradient ($\Delta p$) that drives ATP synthesis via ATP synthase.

Step 3 : Detailed Explanation:

• Experiment 3 (Untreated): In the untreated control, the ETC functions at normal capacity. Electrons from both NADH (entering at Complex I) and $FADH_2$ (entering at Complex II) flow smoothly through ubiquinone, Complex III, cytochrome C, and Complex IV to reduce oxygen.
This generates the maximum proton gradient and yields the highest amount of ATP.

• Experiment 1 (Chemical X): Chemical X blocks electron transfer from Complex I to ubiquinone. This stops NADH oxidation from contributing to the proton gradient.
However, $FADH_2$ can still feed electrons into the ETC at Complex II. These electrons pass through ubiquinone to Complexes III and IV, allowing some proton pumping and resulting in a reduced but significant amount of ATP synthesis.

• Experiment 2 (Chemical Y): Chemical Y blocks the flow of electrons from Complex III to cytochrome C. Because all electrons, whether originating from Complex I (NADH) or Complex II ($FADH_2$), must pass through Complex III to proceed further, this block halts the entire downstream respiratory chain.
As a result, electron flow is completely stopped, proton pumping is minimized, and ATP synthesis drops to near zero.

Step 4 : Final Answer:
Comparing the three experiments, we have: Experiment 2 (least ATP) $<$ Experiment 1 (intermediate ATP) $<$ Experiment 3 (maximum ATP).
This matches Option (A).