L-methylmalonyl-CoA

Definition

L-methylmalonyl-CoA is an intermediate metabolite that plays a crucial role in the catabolism of triacylglycerols through the process of β-oxidation. It is formed during the breakdown of certain amino acids and odd-chain fatty acids.

5 Must Know Facts For Your Next Test

1. L-methylmalonyl-CoA is an intermediate in the catabolism of the amino acids isoleucine, valine, threonine, and methionine, as well as odd-chain fatty acids.
2. The conversion of propionyl-CoA to L-methylmalonyl-CoA is catalyzed by the enzyme propionyl-CoA carboxylase, which requires the cofactor biotin.
3. L-methylmalonyl-CoA is then converted to succinyl-CoA, which can enter the citric acid cycle for further energy production.
4. Deficiencies in the enzymes involved in the metabolism of L-methylmalonyl-CoA can lead to the accumulation of toxic metabolites, causing the genetic disorder methylmalonic acidemia.
5. The regulation of L-methylmalonyl-CoA levels is crucial for maintaining proper cellular function and energy homeostasis.

Review Questions

• Explain the role of L-methylmalonyl-CoA in the catabolism of triacylglycerols through β-oxidation.
  • L-methylmalonyl-CoA is an intermediate metabolite that is formed during the breakdown of certain amino acids and odd-chain fatty acids, which are released from triacylglycerols during the process of β-oxidation. The conversion of propionyl-CoA to L-methylmalonyl-CoA is a key step in the catabolism of these molecules, as L-methylmalonyl-CoA is then further converted to succinyl-CoA, which can enter the citric acid cycle to generate ATP through oxidative phosphorylation. The proper metabolism of L-methylmalonyl-CoA is essential for maintaining energy homeostasis and preventing the accumulation of toxic metabolites.
• Describe the enzymatic conversion of propionyl-CoA to L-methylmalonyl-CoA and the importance of the cofactor biotin in this reaction.
  • The conversion of propionyl-CoA to L-methylmalonyl-CoA is catalyzed by the enzyme propionyl-CoA carboxylase, which requires the cofactor biotin. Biotin acts as a carrier of the carboxyl group, transferring it from bicarbonate to propionyl-CoA to form L-methylmalonyl-CoA. This reaction is a crucial step in the catabolism of certain amino acids and odd-chain fatty acids, as L-methylmalonyl-CoA is then further metabolized to succinyl-CoA, which can enter the citric acid cycle. The proper functioning of this enzymatic pathway is essential for maintaining cellular energy production and preventing the accumulation of potentially toxic metabolites.
• Analyze the potential consequences of a deficiency in the enzymes involved in the metabolism of L-methylmalonyl-CoA and how this can lead to the genetic disorder methylmalonic acidemia.
  • A deficiency in the enzymes responsible for the metabolism of L-methylmalonyl-CoA, such as propionyl-CoA carboxylase or methylmalonyl-CoA mutase, can lead to the accumulation of toxic metabolites, including methylmalonic acid. This genetic disorder, known as methylmalonic acidemia, can have severe clinical manifestations, such as developmental delays, neurological complications, and life-threatening metabolic crises. The inability to properly convert L-methylmalonyl-CoA to succinyl-CoA and integrate it into the citric acid cycle disrupts cellular energy production, leading to the buildup of harmful substances and the impairment of various physiological processes. Understanding the role of L-methylmalonyl-CoA in this metabolic pathway is crucial for diagnosing and managing this inherited metabolic disorder.

Related terms

β-Oxidation: The metabolic pathway that breaks down fatty acids to generate acetyl-CoA, which can then enter the citric acid cycle to produce ATP.

Odd-Chain Fatty Acids: Fatty acids that have an odd number of carbon atoms, which require a different metabolic pathway for degradation compared to even-chain fatty acids.

Propionyl-CoA: An intermediate metabolite formed during the breakdown of certain amino acids and odd-chain fatty acids, which is then converted to L-methylmalonyl-CoA.