CoA biosynthesis requires compounds from two other pathways: aspartate metabolism and valine biosynthesis. It requires a beta-alanine and R-pantoate. The compound (R)-pantoate is generated in two reactions, as shown by the interaction of alpha-ketoisovaleric acid, 5,10 methylene-THF, and water through a 3-methyl-2-oxobutanoate hydroxymethyltransferase resulting in a tetrahydrofolic acid and a 2-dehydropantoate. This compound interacts with hydrogen through an NADPH-driven acetohydroxy acid isomeroreductase resulting in the release of NADP and R-pantoate. On the other hand L-aspartic acid interacts with a hydrogen ion and gets decarboxylated through an aspartate 1-decarboxylase resulting in a carbon dioxide and a beta-alanine. beta-Alanine and R-pantoate interact with an ATP-driven pantothenate synthetase resulting in pyrophosphate, AMP, hydrogen ion, and pantothenic acid. Pantothenic acid is phosphorylated through an ATP-driven pantothenate kinase resulting in an ADP, a hydrogen ion, and D-4'-phosphopantothenate. This compound interacts with a CTP and a L-cysteine resulting in a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a hydrogen ion, a pyrophosphate, a CMP, and 4-phosphopantothenoylcysteine. The latter compound interacts with a hydrogen ion through a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a carbon dioxide release and a 4-phosphopantetheine. This compound interacts with an ATP, hydrogen ion, and a phosphopantetheine adenylyltransferase resulting in a release of pyrophosphate, and dephospho-CoA. Dephospho-CoA reacts with an ATP driven dephospho-CoA kinase resulting in an ADP, a hydrogen ion, and a coenzyme A. Coenzyme A is converted by beta-alanine ligase and a kinase to (R)-4'-phosphopantothenate. These kinases are inhibited by negative feedback by CoA, this is the primary regulation of CoA biosynthesis. L-cysteine is added to (R)-4'-phosphopantothenate to form R-4'-phosphopantothenoyl-L-cysteine (PPC). PPC is then decarboxylated to 4'-phosphopantetheine then converted to CoA by a dephospho-CoA Kinase. The enzymes of this pathway are necessary for growth.

Pantothenate and CoA Biosynthesis References