Coenzyme A

Coenzyme A

Identifiers
CAS Number	85-61-0
ChEBI	CHEBI:15346
ChEMBL	ChEMBL1213327
ChemSpider	6557
DrugBank	DB01992
Jmol 3D model	Interactive image
KEGG	C00010
MeSH	Coenzyme+A
PubChem	6816
UNII	SAA04E81UX
InChI InChI=1S/C21H36N7O16P3S/c1-21(2,16(31)19(32)24-4-3-12(29)23-5-6-48)8-41-47(38,39)44-46(36,37)40-7-11-15(43-45(33,34)35)14(30)20(42-11)28-10-27-13-17(22)25-9-26-18(13)28/h9-11,14-16,20,30-31,48H,3-8H2,1-2H3,(H,23,29)(H,24,32)(H,36,37)(H,38,39)(H2,22,25,26)(H2,33,34,35)/t11-,14-,15-,16?,20-/m1/s1 Key: RGJOEKWQDUBAIZ-DRCCLKDXSA-N InChI=1/C21H36N7O16P3S/c1-21(2,16(31)19(32)24-4-3-12(29)23-5-6-48)8-41-47(38,39)44-46(36,37)40-7-11-15(43-45(33,34)35)14(30)20(42-11)28-10-27-13-17(22)25-9-26-18(13)28/h9-11,14-16,20,30-31,48H,3-8H2,1-2H3,(H,23,29)(H,24,32)(H,36,37)(H,38,39)(H2,22,25,26)(H2,33,34,35)/t11-,14-,15-,16?,20-/m1/s1 Key: RGJOEKWQDUBAIZ-DRCCLKDXBU
SMILES O=C(NCCS)CCNC(=O)C(O)C(C)(C)COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n2cnc1c(ncnc12)N)[C@H](O)[C@@H]3OP(=O)(O)O
Properties
Chemical formula	C21H36N7O16P3S
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]

Biosynthesis

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.
3. PPC is decarboxylated to 4'-phosphopantetheine by phosphopantothenoylcysteine decarboxylase (PPC-DC; CoaC)
4. 4'-phosphopantetheine is adenylylated 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

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]

Function

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]

Non-exhaustive list of coenzyme A-activated acyl groups

• Acetyl-CoA
• fatty acyl-CoA (activated form of all fatty acids; only the CoA esters are substrates for important reactions such as mono-, di-, and triacylglycerol synthesis, carnitine palmitoyl transferase, and cholesterol esterification)
  • Propionyl-CoA
  • Butyryl-CoA
  • Myristoyl-CoA
  • Crotonyl-CoA
• Acetoacetyl-CoA
• Coumaroyl-CoA (used in flavonoid and stilbenoid biosynthesis)
• Benzoyl-CoA
• Phenylacetyl-CoA
• Acyl derived from dicarboxylic acids
  • Malonyl-CoA
  • Succinyl-CoA (used in heme biosynthesis)
  • Hydroxymethylglutaryl-CoA (used in isoprenoid biosynthesis)
  • Pimelyl-CoA (used in biotin biosynthesis)

Additional images

• 

  Coenzyme A

References

1. Matthew Daugherty, Boris Polanuyer, Michael Farrell, Michael Scholle, Athanasios Lykidis, Valérie de Crécy-Lagard and Andrei Osterman (2002). "Complete Reconstitution of the Human Coenzyme A Biosynthetic Pathway via Comparative Genomics". The Journal of Biological Chemistry 277 (24): 21431–21439. doi:10.1074/jbc.M201708200. PMID 11923312.
2. Leonardi R, Zhang YM, Rock CO, Jackowski S (2005). "Coenzyme A: back in action". Progress in Lipid Research 44 (2-3): 125–153. doi:10.1016/j.plipres.2005.04.001. PMID 15893380.
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. doi:10.1074/jbc.M109.080556. PMC 2804320. PMID 19933275.

Bibliography

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