This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: CoA biosynthesis
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Coenzyme A Biosynthesis|
Coenzyme A (CoA) is a cofactor of ubiquitous occurrence in plants, bacteria, and animals needed in a large number of enzymatic reactions central to intermediary metabolism, including the oxidation of fatty acids, carbohydrates, and amino acids. Coenzyme A is the common acyl carrier in prokaryotic and eukaryotic cells required for a multitude of reactions for both biosynthetic and degradative pathways amongst others forming derivatives that are key intermediates in energy metabolism [Rubio06].
The biosynthesis of CoA is of equal importance with regard to its recognition as a target for antibacterial drug discovery and to the association of human neurodegenerative disorder with mutations in EC 22.214.171.124, pantothenate kinase [Leonardi05].
About This Pathway
The CoA biosynthesis precursor 3-methyl-2-oxobutanoate is an intermediate in the synthesis of L-valine (see L-valine biosynthesis). This compound is converted in two steps to (R)-pantoate, as shown in phosphopantothenate biosynthesis I. The latter is converted into (R)-4'-phosphopantothenate is two steps, involving a β-alanine ligase and a kinase. In most organsims the ligase acts before the kinase (EC 126.96.36.199, pantoate—β-alanine ligase (AMP-forming) followed by EC 188.8.131.52, pantothenate kinase, as described in phosphopantothenate biosynthesis I and phosphopantothenate biosynthesis II. However, in archaea the order is reversed, and EC 184.108.40.206, pantoate kinase acts before EC 220.127.116.11, 4-phosphopantoate—β-alanine ligase, as described in phosphopantothenate biosynthesis III.
The kinases are feedback inhibited by CoA itself, accounting for the primary regulatory mechanism of CoA biosynthesis. The addition of L-cysteine to (R)-4'-phosphopantothenate, resulting in the formation of R-4'-phosphopantothenoyl-L-cysteine (PPC), is followed by decarboxylation of PPC to 4'-phosphopantetheine. The ultimate reaction is catalyzed by EC 18.104.22.168, dephospho-CoA kinase, which converts 4'-phosphopantetheine to CoA. All enzymes of this pathway are essential for growth.
The reactions in the biosynthetic route towards CoA are identical in most organisms, although there are differences in the functionality of the involved enzymes. In plants every step is catalyzed by single monofunctional enzymes, whereas in bacteria and mammals bifunctional enzymes are often employed [Rubio06].
About this pathway in yeast
The conversion of R-4'-phosphopantothenoyl-L-cysteine to 4'-phosphopantetheine is catalyzed by EC 22.214.171.124, phosphopantothenoylcysteine decarboxylase. In Saccharomyces cerevisiae this is a unique heterotrimeric enzyme encoded by three genes, CAB3, SIS2 and VHS3 which although similar in structure are irreplaceable and fulfill distinctive essential functions in the protein complex. Two of the three genes, SIS2 and VHS3, are moonlighting proteins which are not only involved as PPCDC subunits in CoA biosynthesis but also known to be inhibitors/negative regulators of the serine/threonine protein phosphatase Ppz1 [deNadal98, Arino02, Ruiz04]. Hence, this enzyme complex stands as an example of cross-talks between metabolic and signaling pathways indicating the possibility of exerting regulatory influence from one pathway to another [Osterman09].
Variants: coenzyme A biosynthesis II (mammalian)
Created 07-Oct-2003 by Arnaud M , SRI International
Reviewed 24-Oct-2006 by Foerster H , TAIR
Revised 12-Jun-2008 by Keseler I , SRI International
Revised 05-Mar-2013 by Foerster H , Boyce Thompson Institute
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