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.