Question

Valine and isoleucine give rise to propionyl CoA, a precursor of succinyl CoA. A disease related to a defect in this conversion is methylmalonic aciduria. Some patients respond to megadoses of vitamin \(\mathrm{B}_{12}\). Which of the following statements about the conversion of propionyl CoA to succinyl CoA is/are correct? A. The first step in the conversion is a biotin-dependent carboxylation. B. Some methylmalonic aciduria patients respond to \(\mathrm{B}_{12}\) because the defect in the mutase converting malonyl CoA to succinyl CoA is poor binding of the cofactor. C. The same pathway of propionyl CoA to succinyl CoA is part of the metabolism of odd-chain fatty acids. D. All of the above. E. None of the above.

Short answer

Answer: D. All of the above.

Step-by-step solution

Analyze the conversion of propionyl CoA to succinyl CoA

To determine the correct statements, we must first look at the pathway that converts propionyl CoA to succinyl CoA. The conversion occurs in three main steps: 1. Biotin-dependent carboxylation of propionyl CoA to form D-methylmalonyl CoA. 2. Isomerization (with vitamin B12 as a cofactor): conversion of D-methylmalonyl CoA to L-methylmalonyl CoA. 3. Mutase reaction (again, with vitamin B12 as a cofactor): conversion of L-methylmalonyl CoA to succinyl CoA.

Evaluate statement A

Statement A says, "The first step in the conversion is a biotin-dependent carboxylation." This statement is true, as we have seen in the first step of the pathway mentioned above. So, statement A is correct.

Evaluate statement B

Statement B says, "Some methylmalonic aciduria patients respond to \(\mathrm{B}_{12}\) because the defect in the mutase converting malonyl CoA to succinyl CoA is poor binding of the cofactor." This statement is also true: methylmalonic aciduria occurs due to a deficiency in the enzyme methylmalonyl-CoA mutase or its cofactor, vitamin B12. Some patients respond to megadoses of vitamin B12 because the problem is with the poor cofactor binding, and providing more cofactor improves enzyme function. Thus, statement B is correct.

Evaluate statement C

Statement C says, "The same pathway of propionyl CoA to succinyl CoA is part of the metabolism of odd-chain fatty acids." This is true because, during the metabolism of odd-chain fatty acids, propionyl CoA is generated as a by-product, and it undergoes the same pathway to be converted to succinyl CoA. Therefore, statement C is also correct.

Final Step: Determine the correct answer choice

All three statements A, B, and C are correct. This means the correct answer choice is: D. All of the above.

Key concepts

Biochemistry

Biochemistry underpins our understanding of life's molecular foundations, including how molecules like propionyl CoA are metabolized within our cells. The conversion of propionyl CoA to succinyl CoA is an essential metabolic process, particularly for the degradation of certain amino acids and odd-chain fatty acids.

Propionyl CoA is an intermediate that enters the citric acid cycle after being converted to succinyl CoA, thus connecting various metabolic pathways. The reactions involved are catalyzed by highly specific enzymes and require the assistance of coenzymes, such as biotin and vitamin B12, which facilitate the reactions at a biochemical level.

Metabolic Pathways

Metabolic pathways are a series of connected biochemical reactions that occur within a biological organism, allowing it to grow, reproduce, maintain its structures, and respond to environmental changes.

In the context of the propionyl CoA to succinyl CoA conversion, we see an intricate pathway that includes a biotin-dependent carboxylation followed by an isomerization that requires vitamin B12. These steps highlight the complexity and interdependence of the metabolic pathways and demonstrate the importance of nutrients that act as coenzymes aiding in the enzymatic functions necessary for metabolism.

Vitamin B12 and Biotin

Vitamins B12 and biotin play crucial roles as coenzymes in the human body. They are indispensable for the proper functioning of several enzymes involved in metabolic pathways.

Vitamin B12

Vitamin B12 is a coenzyme for mutase reactions, such as the conversion of L-methylmalonyl CoA to succinyl CoA. Deficiencies in vitamin B12 can result in metabolic disorders, one of which is methylmalonic aciduria.

Biotin

Biotin is essential for carboxylase enzymes that catalyze carboxylation reactions. The first step of turning propionyl CoA into succinyl CoA involves biotin-dependent carboxylation, demonstrating biotin's vital role in this and other metabolic processes.

Methylmalonic Aciduria

Methylmalonic aciduria is a genetic metabolic disorder characterized by the accumulation of methylmalonic acid in the body due to a deficiency in the enzyme methylmalonyl-CoA mutase or a defect in its coenzyme, vitamin B12.

Individuals with this condition may exhibit various symptoms, such as developmental delays, which can be alleviated in some cases with vitamin B12 supplements. Understanding the biochemistry behind this disorder not only aids in treating it but also contributes to our broader knowledge of human metabolism and the impact of vitamins on our health.