Question

The vitamin $\text{B}_{12}$ deficiency will lead to the accumulation of which of the following metabolites?}

• A. Pyruvic acid
• B. Methyl malonic acid
• C. $\alpha$-Keto glutarate
• D. Biotin

Hint:

Vitamin $\text{B}_{12}$ is a cofactor for methylmalonyl-CoA mutase.
When $\text{B}_{12}$ is deficient, this conversion is blocked, leading to the accumulation of methylmalonic acid (MMA) in tissues and urine.

Answer 1

The Correct Option is B

Step 1: Understanding the Concept:
Vitamin $\text{B}_{12}$ (cobalamin) is an essential water-soluble vitamin that serves as a cofactor for key enzymatic reactions in human and animal metabolism.
A deficiency of this vitamin blocks these metabolic pathways, leading to the accumulation of upstream intermediates.

Step 2: Detailed Explanation:
In cells, adenosylcobalamin (a coenzyme form of vitamin $\text{B}_{12}$) is required by the mitochondrial enzyme methylmalonyl-CoA mutase.
This enzyme catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, which is a key step in the breakdown of odd-chain fatty acids, amino acids (isoleucine, valine, threonine, methionine), and cholesterol.
Under conditions of vitamin $\text{B}_{12}$ deficiency, the activity of methylmalonyl-CoA mutase is severely reduced.
This metabolic block prevents the conversion of methylmalonyl-CoA into succinyl-CoA.
As a result, methylmalonyl-CoA accumulates in the mitochondria and is hydrolyzed to methylmalonic acid (MMA).
The accumulation of methylmalonic acid leads to elevated levels of MMA in the blood (methylmalonic acidemia) and urine (methylmalonic aciduria), serving as a diagnostic marker for vitamin $\text{B}_{12}$ deficiency.

Step 3: Final Answer:
Vitamin $\text{B}_{12}$ deficiency leads to the accumulation of Methyl malonic acid, which corresponds to Option (B).