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Pathway Description
Pantothenate and CoA Biosynthesis
Escherichia coli
Metabolic Pathway
The 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. 2-dehydropantoate interacts with hydrogen through a 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 a ATP-driven pantothenate kinase resulting in a ADP, a hydrogen ion and D-4'-Phosphopantothenate. The latter 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 the release of carbon dioxide and 4-phosphopantetheine. 4-phosphopantetheine reacts with ATP, hydrogen ion and an phosphopantetheine adenylyltransferase resulting in a release of pyrophosphate, and dephospho-CoA. Dephospho-CoA reacts with an ATP driven dephospho-CoA kinase resulting in a ADP , a hydrogen ion and a Coenzyme A. Dephospho-CoA also reacts with 2-(5''-triphosphoribosyl)-3'-dephosphocoenzyme-A synthase (citG) to form both adenine and 2'-(5-Triphosphoribosyl)-3'-dephospho-CoA. In this pathway, all enzymes are essential for the cell growth. Biosynthetic pathway for producing CoA is same for most organisms (with exception of differences in the functionality of involved enzymes). In plants, every step is catalyzed by monofunctional enzymes instead of biofunctional enzymes.
References
Pantothenate and CoA Biosynthesis References
Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL: An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment. Plant Physiol. 2006 Mar;140(3):830-43. doi: 10.1104/pp.105.072066. Epub 2006 Jan 13.
Pubmed: 16415216
Miller JR, Ohren J, Sarver RW, Mueller WT, de Dreu P, Case H, Thanabal V: Phosphopantetheine adenylyltransferase from Escherichia coli: investigation of the kinetic mechanism and role in regulation of coenzyme A biosynthesis. J Bacteriol. 2007 Nov;189(22):8196-205. doi: 10.1128/JB.00732-07. Epub 2007 Sep 14.
Pubmed: 17873050
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