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Chemical compound
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 (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.
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References.
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