Question

Given below are two statements, one is labelled as Assertion (A) and other one labelled as Reason (R).
Assertion (A) : The "Randle Cycle" describes the inhibition of the glycolysis by fatty acid oxidation.
Reason (R) : Oxidation of fatty acids increases the concentration of citrate that in turn inhibits the phosphofructokinase enzyme of glycolytic pathway.
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:

The Randle Cycle is highly active in cardiac and skeletal muscle tissues during fasting or starvation, conserving limited glucose supplies for glucose-dependent organs like the brain.

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
The Randle Cycle (also known as the glucose-fatty acid cycle) is a metabolic mechanism that regulates fuel selection in animal tissues.
It describes how the oxidation of fatty acids directly suppresses glucose uptake and glycolysis, allowing tissues to prioritize fat as an energy source.

Step 2: Detailed Explanation:
Let us analyze both the Assertion and the Reason:
- Assertion (A): The Randle Cycle describes the metabolic competition between glucose and fatty acids for energy production.
When fatty acid concentration increases, their cellular oxidation inhibits glucose utilization (both glycolysis and glucose oxidation).
Thus, Assertion (A) is true.
- Reason (R): During fatty acid oxidation ($\beta$-oxidation), large amounts of acetyl-CoA and NADH are generated in the mitochondrial matrix.
The high concentration of acetyl-CoA enters the citric acid cycle, leading to an increase in mitochondrial citrate levels.
This excess citrate is transported out of the mitochondria into the cytosol via the tricarboxylate carrier.
In the cytosol, citrate acts as a potent allosteric inhibitor of phosphofructokinase-1 (PFK-1), the key rate-limiting enzyme of glycolysis.
Inhibiting PFK-1 slows down glycolysis, which leads to the accumulation of glucose-6-phosphate. This accumulation subsequently inhibits hexokinase, reducing cellular glucose uptake.
Therefore, Reason (R) is true and directly explains the molecular mechanism behind the Randle Cycle described in Assertion (A).

Step 3: Final Answer:
Both (A) and (R) are true, and (R) is the correct explanation of (A), corresponding to option (A).