Methylmalonic acid

Methylmalonic acid is a dicarboxylic acid formed during amino-acid and odd-chain fatty-acid metabolism. Its accumulation can signal impaired vitamin B₁₂-dependent conversion to succinyl-CoA.

Methylmalonyl-CoA mutase: A mitochondrial enzyme that converts L-methylmalonyl-CoA into succinyl-CoA using adenosylcobalamin. This B₁₂-dependent enzyme lies downstream of methylmalonic acid and is impaired in its accumulation.
Methylmalonic acid test: A laboratory measurement of methylmalonic acid in blood, urine, or both. This test uses the metabolite's rise as evidence of impaired pathway function.
Dicarboxylic acid: An organic acid containing two carboxyl groups. Methylmalonic acid belongs to this chemical class because it contains two carboxyl groups.
Folate deficiency: A state in which the body lacks sufficient folate for DNA synthesis and one-carbon metabolism. Like B₁₂ deficiency, it can raise homocysteine, but it does not typically raise methylmalonic acid.
Methylmalonyl-CoA: A coenzyme A ester formed from propionyl-CoA that can be rearranged into succinyl-CoA. Methylmalonic acid is produced when this pathway intermediate is hydrolyzed.
Vitamin B12 deficiency: A state in which the body lacks sufficient vitamin B₁₂ for normal cellular functions. Deficiency can reduce adenosylcobalamin-dependent breakdown and elevate methylmalonic acid.
Amino acid catabolism: The set of pathways that break down amino acids into energy-producing or biosynthetic intermediates. Valine, isoleucine, methionine, and threonine breakdown can feed the pathway producing methylmalonic acid.
Propionic acidemia: An inherited disorder caused by deficient propionyl-CoA carboxylase activity, leading to propionate-related metabolite accumulation. It disrupts an upstream pathway and produces a different characteristic metabolite pattern.
Propionyl-CoA: A three-carbon acyl-CoA produced during the breakdown of several amino acids and odd-chain fatty acids. It begins the pathway that generates methylmalonyl-CoA and ultimately methylmalonic acid.
Homocysteine: A sulfur-containing amino acid formed during methionine metabolism. Its level is often measured alongside methylmalonic acid to help assess B₁₂ deficiency.

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