Methylmalonyl-CoA

Methylmalonyl-CoA can be synthesized in two ways: • From propionyl-CoA: Methylmalonyl-CoA results from the metabolism of fatty acid with an odd number of carbons, of amino acids valine, isoleucine, methionine, threonine or of cholesterol side-chains, forming Propionyl-CoA. The latter is also formed from propionic acid, which bacteria produce in the intestine. Propionyl CoA + Bicarbonate → Methylmalonyl CoA → Succinyl CoA • From methylmalonic acid: The mitochondrial enzyme acyl-CoA synthetase family member 3 (ACSF3) catalyzes the thioesterification of methylmalonic acid with coenzyme A (CoA) to form methylmalonyl-CoA. == Vitamin B12 ==

Vitamin B12 plays an integral role in this reaction. Coenzyme B12 (adenosyl-cobalamin) is an organometallic form of vitamin B12 and serves as the cofactor of Methylmalonyl-CoA mutase, which is an essential enzyme in the human body. The transformation of Methylmalonyl-CoA to Succinyl-CoA by this enzyme is a radical reaction. == Related diseases ==

Methylmalonic Acidemia (MMA) This disease occurs when methylmalonyl-CoA mutase is unable to isomerize sufficient amounts of methylmalonyl-CoA into succinyl-CoA. This causes a buildup of propionic and/or methylmalonic acid, which has effects on infants ranging from severe brain damage to death. The disease is linked to vitamin B12, which is a cofactor for the enzyme methylmalonyl-CoA mutase. Combined malonic and methylmalonic aciduria (CMAMMA) In combined malonic and methylmalonic aciduria (CMAMMA), mutations in the ACSF3 gene impair the mitochondrial enzyme acyl-CoA synthetase family member 3 (ACSF3), disrupting the conversion of methylmalonic acid to methylmalonyl-CoA and its entry into the citric acid cycle. This leads to accumulation of methylmalonic acid, reduced methylmalonyl-CoA levels and decreased lysine methylmalonylation compared to healthy controls. == References ==