Question

Which of the following statement(s) is/are true about the role of Malonyl CoA in fatty acid metabolism?
(A). It is an inhibitor of the enzyme “Carnitine acyltransferase”
(B). High levels of malonyl CoA suppress fatty acid entry into the mitochondria
(C). High levels of malonyl CoA lead to reduced flux of fatty acids towards triglycerides' biosynthesis
(D). Low levels of malonyl CoA favour fatty acid oxidation

Choose the correct answer from the options given below:

• A. (A), (B) and (D) only.
• B. (A), (B) and (C) only.
• C. (A), (B), (C) and (D).
• D. (B), (C) and (D) only.

Hint:

Malonyl-CoA acts as a metabolic gatekeeper.
When the cell has plenty of energy, malonyl-CoA levels rise to build fatty acids and inhibit CPT-1, ensuring that the newly synthesized fatty acids are not simultaneously degraded.

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
Fatty acid synthesis and fatty acid \( \beta \)-oxidation must be coordinately regulated to prevent a futile cycle, where synthesized fatty acids are immediately transported back into the mitochondria to be oxidized.
Malonyl-CoA, the first committed intermediate of fatty acid biosynthesis, serves as a primary regulatory signal that controls this metabolic switch in animal tissues.

Step 2: Detailed Explanation:
Let us analyze each statement to determine its biochemical validity:
- Statement (A) is true: Malonyl-CoA acts as a potent allosteric inhibitor of Carnitine Palmitoyltransferase I (CPT-1, also known as carnitine acyltransferase I), which resides in the outer mitochondrial membrane.
- Statement (B) is true: CPT-1 is the rate-limiting enzyme of the carnitine shuttle, which catalyzes the transfer of fatty acyl groups from coenzyme A to carnitine. This step is required for fatty acids to cross the inner mitochondrial membrane.
By inhibiting CPT-1, high levels of malonyl-CoA in the cytosol prevent the entry of fatty acyl-CoA molecules into the mitochondrial matrix.
- Statement (C) is false: High levels of malonyl-CoA are synthesized by acetyl-CoA carboxylase (ACC) in response to insulin and high energy levels.
Since malonyl-CoA is the substrate for fatty acid synthase, high levels indicate active de novo lipogenesis.
This increases the synthesis of fatty acids, which are subsequently esterified into triacylglycerols (triglycerides).
Therefore, high levels of malonyl-CoA lead to an increased (not reduced) flux of fatty acids towards triglyceride biosynthesis.
- Statement (D) is true: During fasting or energetic stress, AMPK phosphorylates and inactivates ACC, causing malonyl-CoA levels to fall rapidly.
This drop relieves the allosteric inhibition on CPT-1, allowing fatty acyl-CoAs to enter the mitochondria for \( \beta \)-oxidation to produce ATP.
Thus, statements (A), (B), and (D) are true, while (C) is false.

Step 3: Final Answer:
The correct option is (A) (A), (B) and (D) only.