• Source: Methylmalonyl-CoA

Methylmalonyl-CoA is the thioester consisting of coenzyme A linked to methylmalonic acid. It is an important intermediate in the biosynthesis of succinyl-CoA, which plays an essential role in the tricarboxylic acid cycle (aka the Citric Acid Cycle, or Krebs Cycle).




Biosynthesis and metabolism



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 and bicarbonate are converted to Methylmalonyl-CoA by the enzyme propionyl-CoA Carboxylase. It then is converted into succinyl-CoA by methylmalonyl-CoA mutase (MUT). This reaction is a reversible isomerization. In this way, the compound enters the Citric Acid Cycle. The following diagram demonstrates the aforementioned reaction:
Propionyl CoA + Bicarbonate → Methylmalonyl CoA → Succinyl 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)

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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)

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In the metabolic disease combined malonic and methylmalonic aciduria (CMAMMA), acyl-CoA synthetase family member 3 (ACSF3) is reduced, which converts toxic methylmalonic acid to methylmalonyl-CoA and thus supplies it to the citric acid cycle. The result is an accumulation of methylmalonic acid.




References

Kata Kunci Pencarian:

• Vitamin B12
• Gabungan malonik dan metilmalonik aciduria
• Asam metilmalonat
• Sianokobalamin
• Methylmalonyl-CoA
• Methylmalonyl-CoA mutase
• Methylmalonyl CoA epimerase
• Methylmalonyl-CoA decarboxylase
• Succinyl-CoA
• Propionyl-CoA
• Methylmalonyl-CoA carboxytransferase
• Propionic acidemia
• Methylmalonic acidemias
• Methylmalonyl-CoA mutase deficiency