title: Malonyl-CoA
text: # Malonyl-CoA
  
  Malonyl-CoA is a coenzyme A derivative of malonic acid.
  
  ## Functions
  
  It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis.
  
  ### Cytosolic fatty acid biosynthesis
  
  Malonyl-CoA provides 2-carbon units to fatty acids and commits them to fatty acid chain synthesis.
  
  Malonyl-CoA is formed by carboxylating acetyl-CoA using the enzyme acetyl-CoA carboxylase. One molecule of acetyl-CoA joins with a molecule of bicarbonate, requiring energy rendered from ATP.
  
  Malonyl-CoA is utilised in fatty acid biosynthesis by the enzyme malonyl coenzyme A:acyl carrier protein transacylase (MCAT). MCAT serves to transfer malonate from malonyl-CoA to the terminal thiol of holo-acyl carrier protein (ACP).
  
  ### Mitochondrial fatty acid synthesis
  
  Malonyl-CoA is formed in the first step of mitochondrial fatty acid synthesis (mtFASII) from malonic acid by malonyl-CoA synthetase (ACSF3).
  
  ### Polyketide biosynthesis
  
  MCAT is also involved in bacterial polyketide biosynthesis. The enzyme MCAT together with an acyl carrier protein (ACP), and a polyketide synthase (PKS) and chain-length factor heterodimer, constitutes the minimal PKS of type II polyketides.
  
  ### Regulation
  
  Malonyl-CoA is a highly regulated molecule in fatty acid synthesis; as such, it inhibits the rate-limiting step in beta-oxidation of fatty acids. Malonyl-CoA inhibits fatty acids from associating with carnitine by regulating the enzyme carnitine acyltransferase, thereby preventing them from entering the mitochondria, where fatty acid oxidation and degradation occur.
  
  ## Related diseases
  
  Malonyl-CoA plays a special role in the mitochondrial clearance of toxic malonic acid in the metabolic disorder combined malonic and methylmalonic aciduria (CMAMMA). In CMAMMA due to ACSF3, malonyl-CoA synthetase is decreased, which can generate malonyl-CoA from malonic acid, which can then be converted to acetyl-CoA by malonyl-CoA decarboxylase. In contrast, in CMAMMA due to malonyl-CoA decarboxylase deficiency, malonyl-CoA decarboxylase is decreased, which converts malonyl-CoA to acetyl-CoA.
  
  $\mathrm {Malonic\ acid+CoA+ATP\ {\xrightarrow[{ACSF3}]{Malonyl{-}CoA\ Synthetase}}\ Malonyl{-}CoA\ {\xrightarrow[{MLYCD}]{Malonyl-CoA\ Decarboxylase}}\ Acetyl{-}CoA}$
  
  