Question

Given below are two statements, one is labelled as Assertion (A) and other one labelled as Reason (R).
Assertion (A): In the early part of the twentieth century, 2,4-Dinitrophenol (DNP) was prescribed as a “diet pill” for weight loss.
Reason (R): The DNP reduces metabolic rate by uncoupling oxidative phosphorylation from electron transport.
In light of the above statements, choose the correct answer from the options given below:

• A. Both (A) and (R) are true and (R) is the correct explanation of (A).
• B. Both (A) and (R) are true but (R) is NOT the correct explanation of (A).
• C. (A) is true but (R) is false.
• D. (A) is false but (R) is true.

Hint:

Uncoupling agents like DNP, FCCP, and thermogenin (in brown adipose tissue) always increase oxygen consumption and metabolic rate while decreasing the efficiency of ATP synthesis, producing significant heat.

Answer 1

The Correct Option is C

Step 1: Understanding the Concept:
Oxidative phosphorylation depends on chemiosmotic coupling, where the energy derived from the mitochondrial electron transport chain is stored as a proton-motive force (an electrochemical gradient of protons across the inner mitochondrial membrane).
ATP synthase utilizes this gradient to synthesize ATP. Uncoupling agents are lipophilic compounds that can bind protons, diffuse across the lipid bilayer, and dissipate this electrochemical gradient, thereby disconnecting electron transport from ATP synthesis.

Step 2: Detailed Explanation:
1. Analysis of Assertion (A): During the 1930s, 2,4-Dinitrophenol (DNP) was extensively marketed and prescribed as an effective over-the-counter diet pill.
By uncoupling mitochondria, it caused the body to burn through fat and carbohydrate stores at an extremely high rate, leading to rapid weight loss.
However, due to severe adverse effects including fatal hyperthermia and cataracts, it was banned by the FDA. The historical fact described in Assertion (A) is true.
2. Analysis of Reason (R): DNP is a weak acid that is highly soluble in lipids.
In the intermembrane space, where the proton concentration is high, DNP becomes protonated. It then diffuses across the inner mitochondrial membrane into the matrix, where the lower proton concentration causes it to release the proton.
This shuttle mechanism directly short-circuits the proton gradient.
To compensate for the loss of ATP synthesis, the cell must run its catabolic pathways (glycolysis, glycogenolysis, citric acid cycle, and fat oxidation) at maximum capacity to generate sufficient ATP.
Therefore, DNP dramatically increases (rather than reduces) the cellular metabolic rate and oxygen consumption.
The energy that would normally be captured in the high-energy phosphate bonds of ATP is instead dissipated as heat, explaining the risk of lethal hyperthermia.
Since the Reason states that DNP reduces metabolic rate, it is biologically incorrect.

Step 3: Final Answer:
Assertion (A) is true, but Reason (R) is false. This corresponds to option (C).