If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Coenzyme A Biosynthesis|
Expected Taxonomic Range: Viridiplantae
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].
Pantothenate (vitamin B5) is the universal precursor for the synthesis of the 4'-phosphopantetheine moiety of CoA and of acyl carrier proteins. Only plants and microorganisms can synthesize pantothenate de novo. In contrast to the bacterial biosynthesis of pantothenate (phosphopantothenate biosynthesis I), plant pathways for pantothenate formation are incomplete.
Coenzyme A (CoA), derived from pantothenate 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.
About This Pathway
Feeding studies in Pisum sativum leaf discs support the existence of a similar biosynthesis pathway of pantothenate via pantoate: when fed with [14C]valine, the radiolabel was incorporated into α-oxoisovalerate, oxopantoate and pantoate [Jones94a]. The last enzyme of the pathway: pantothenate synthetase catalyzes the formation of pantothenate from pantoate and β-alanine. The origin of plant β-alanine is uncertain but appears to be different from that of bacteria which synthesize it from L-aspartate. Instead plants seem to produce β-alanine from a variety of other sources, like polyamines, uracil and propionate (see β-alanine biosynthesis II).
The biosynthesis of CoA is carried out from pantothenate in five enzymatic steps. All of the enzymes involved have been recently identified in Arabidopsis thaliana and the metabolic sequence confirmed in vitro by combining the recombinant enzymes [Kupke03].
Pantothenate kinase, the enzyme catalyzing the first step, phosphorylates 4'-phosphopantothenate to 4'-phosphopantothenate followed by the addition of cysteine resulting in the formation of (R)-4'-phospho-N-pantothenoylcysteine (PPC). PPC is decarboxylated in the next reaction to 4'-phosphopantetheine and then in two successive reactions converted to CoA by the enzymatic action of 4'-phosphopantetheine adenylyltransferase and dephospho-CoA kinase [Kupke03] [Steinbacher03]. The reactions in the biosynthetic route towards CoA parallel the reaction sequence obtained in bacteria but differ regarding the functionality of the involved enzymes. In plants every step is catalyzed by single monofunctional enzymes, whereas in bacteria and mammals bifunctional enzymes are employed [Rubio06].
Unification Links: AraCyc:PWY-4221
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Steinbacher03: Steinbacher S, Hernandez-Acosta P, Bieseler B, Blaesse M, Huber R, Culianez-Macia FA, Kupke T (2003). "Crystal structure of the plant PPC decarboxylase AtHAL3a complexed with an ene-thiol reaction intermediate." J Mol Biol 327(1);193-202. PMID: 12614618
Alber02: Alber BE, Fuchs G (2002). "Propionyl-coenzyme A synthase from Chloroflexus aurantiacus, a key enzyme of the 3-hydroxypropionate cycle for autotrophic CO2 fixation." J Biol Chem 277(14);12137-43. PMID: 11821399
Armando12: Armando JW, Boghigian BA, Pfeifer BA (2012). "LC-MS/MS quantification of short-chain acyl-CoA's in Escherichia coli demonstrates versatile propionyl-CoA synthetase substrate specificity." Lett Appl Microbiol 54(2);140-8. PMID: 22118660
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Chetnani09: Chetnani B, Das S, Kumar P, Surolia A, Vijayan M (2009). "Mycobacterium tuberculosis pantothenate kinase: possible changes in location of ligands during enzyme action." Acta Crystallogr D Biol Crystallogr 65(Pt 4);312-25. PMID: 19307712
Ciulli07: Ciulli A, Chirgadze DY, Smith AG, Blundell TL, Abell C (2007). "Crystal structure of Escherichia coli ketopantoate reductase in a ternary complex with NADP+ and pantoate bound: substrate recognition, conformational change, and cooperativity." J Biol Chem 282(11);8487-97. PMID: 17229734
Cronan82: Cronan JE, Littel KJ, Jackowski S (1982). "Genetic and biochemical analyses of pantothenate biosynthesis in Escherichia coli and Salmonella typhimurium." J Bacteriol 149(3);916-22. PMID: 7037743
Daugherty02: Daugherty M, Polanuyer B, Farrell M, Scholle M, Lykidis A, de Crecy-Lagard V, Osterman A (2002). "Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics." J Biol Chem 277(24);21431-9. PMID: 11923312
deNadal98: de Nadal E, Clotet J, Posas F, Serrano R, Gomez N, Arino J (1998). "The yeast halotolerance determinant Hal3p is an inhibitory subunit of the Ppz1p Ser/Thr protein phosphatase." Proc Natl Acad Sci U S A 95(13);7357-62. PMID: 9636153
Elischewski99: Elischewski F, Puhler A, Kalinowski J (1999). "Pantothenate production in Escherichia coli K12 by enhanced expression of the panE gene encoding ketopantoate reductase." J Biotechnol 75(2-3);135-46. PMID: 10553653
Geerlof99: Geerlof A, Lewendon A, Shaw WV (1999). "Purification and characterization of phosphopantetheine adenylyltransferase from Escherichia coli." J Biol Chem 1999;274(38);27105-11. PMID: 10480925
Genschel99: Genschel U, Powell CA, Abell C, Smith AG (1999). "The final step of pantothenate biosynthesis in higher plants: cloning and characterization of pantothenate synthetase from Lotus japonicus and Oryza sativum (rice)." Biochem J 341 ( Pt 3);669-78. PMID: 10417331
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