Coenzyme A

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Coenzyme A
Coenzym A.svg
3D model (JSmol)
ECHA InfoCard 100.001.472
MeSH Coenzyme+A
Molar mass 767.535
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Coenzyme A (CoA, CoASH, or HSCoA) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester, such as acetyl-CoA) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenate, and adenosine triphosphate (ATP).[1]


In all living organisms, Coenzyme A is synthesized in a five-step process that requires four molecules of ATP, from pantothenate and cysteine:[2]

  1. Pantothenate (vitamin B5) is phosphorylated to 4'-phosphopantothenate by the enzyme pantothenate kinase (PanK; CoaA; CoaX)
  2. A cysteine is added to 4'-phosphopantothenate by the enzyme phosphopantothenoylcysteine synthetase (PPCS; CoaB) to form 4'-phospho-N-pantothenoylcysteine (PPC).
  3. PPC is decarboxylated to 4'-phosphopantetheine by phosphopantothenoylcysteine decarboxylase (PPC-DC; CoaC)
  4. 4'-phosphopantetheine is adenylylated (or more properly, AMPylated) to form dephospho-CoA by the enzyme phosphopantetheine adenylyl transferase (PPAT; CoaD)
  5. Finally, dephospho-CoA is phosphorylated to coenzyme A by the enzyme dephosphocoenzyme A kinase (DPCK; CoaE).

Enzyme nomenclature abbreviations in parentheses represent eukaryotic and prokaryotic enzymes respectively. In some plants and bacteria, including Escherichia coli, pantothenate can be synthesised de novo and is therefore not considered essential.

Discovery of structure[edit]

Structure of coenzyme A: 1: 3'-phosphoadenosine. 2: diphosphate, organophosphate anhydride. 3: pantoic acid. 4: β-alanine. 5: β-cystamine.

The structure of coenzyme A was identified in the early 1950s at the Lister Institute, London, together with other workers at Harvard Medical School and Massachusetts General Hospital.[3]


Since coenzyme A is, in chemical terms, a thiol, it can react with carboxylic acids to form thioesters, thus functioning as an acyl group carrier. It assists in transferring fatty acids from the cytoplasm to mitochondria. A molecule of coenzyme A carrying an acetyl group is also referred to as acetyl-CoA. When it is not attached to an acyl group, it is usually referred to as 'CoASH' or 'HSCoA'.

Coenzyme A is also the source of the phosphopantetheine group that is added as a prosthetic group to proteins such as acyl carrier protein and formyltetrahydrofolate dehydrogenase.[4][5]

Use in biological research[edit]

Coenzyme A is available from various chemical suppliers as the free acid and or lithium or sodium salts. The free acid of coenzyme A is detectably unstable, with ~5% degradation observed after 6 months when stored at -20˚C,[6] and near complete degradation after 1 month at 37˚C. [7] The lithium and sodium salts of CoA are more stable, with negligible degradation noted over several months at various temperatures [8] Aqueous solutions of coenzyme A are unstable above pH 8, with 31% of activity lost after 24 hours at 25˚C and pH 8. CoA stock solutions are relatively stable when frozen at pH 2-6. The major route of CoA activity loss is likely the air oxidation of CoA to CoA disulfides. CoA mixed disulfides, such as CoA-S-S-glutathione, are commonly noted contaminants in commercial preparations of CoA.,[6] Free CoA can be regenerated from CoA disulfide and mixed CoA disulfides with reducing agents such as DTT or BME.

Non-exhaustive list of coenzyme A-activated acyl groups[edit]


  1. ^ Matthew Daugherty; Boris Polanuyer; Michael Farrell; Michael Scholle; Athanasios Lykidis; Valérie de Crécy-Lagard; Andrei Osterman (2002). "Complete Reconstitution of the Human Coenzyme A Biosynthetic Pathway via Comparative Genomics". The Journal of Biological Chemistry. 277 (24): 21431–21439. PMID 11923312. doi:10.1074/jbc.M201708200. 
  2. ^ Leonardi R, Zhang YM, Rock CO, Jackowski S (2005). "Coenzyme A: back in action". Progress in Lipid Research. 44 (2-3): 125–153. PMID 15893380. doi:10.1016/j.plipres.2005.04.001. 
  3. ^ Baddiley, J.; Thain, E. M.; Novelli, G. D.; Lipmann, F. (1953). "Structure of Coenzyme A". Nature. 171 (4341): 76. doi:10.1038/171076a0. 
  4. ^ Elovson J, Vagelos PR (July 1968). "Acyl carrier protein. X. Acyl carrier protein synthetase". J. Biol. Chem. 243 (13): 3603–11. PMID 4872726. 
  5. ^ Strickland KC, Hoeferlin LA, Oleinik NV, Krupenko NI, Krupenko SA (January 2010). "Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase". J. Biol. Chem. 285 (3): 1627–33. PMC 2804320Freely accessible. PMID 19933275. doi:10.1074/jbc.M109.080556. 
  6. ^ a b Dawson, R. M. C. (1989). Data for biochemical research. Oxford: Clarendon Press. p. 118-119. ISBN 0-19-855299-8. 
  7. ^ "Datasheet for free acid coenzyme A" (PDF). Oriental Yeast Co., LTD. 
  8. ^ "Datasheet for lithium salt coenzyme A" (PDF). Oriental Yeast Co., LTD. 


  • Nelson, David L.; Cox, Michael M. (2005). Lehninger: Principles of Biochemistry (4th ed.). New York: W.H. Freeman. ISBN 0-7167-4339-6.