Coenzyme A

Coenzyme A
Identifiers
CAS number	85-61-0 Y
PubChem	6816
ChemSpider	6557 Y
UNII	SAA04E81UX Y
DrugBank	DB01992
KEGG	C00010 N
MeSH	Coenzyme+A
ChEMBL	CHEMBL1213327 N
Jmol-3D images	Image 1
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
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 Y Key: RGJOEKWQDUBAIZ-DRCCLKDXSA-N Y 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
Properties
Molecular formula	C21H36N7O16P3S
Molar mass	767.535
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
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 sequenced genomes 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.^[1] It is adapted from cysteamine, pantothenate, and adenosine triphosphate.

Biosynthesis

Coenzyme A is synthesized in a five-step process from pantothenate and cysteine:

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 (PPC-DC; CoaB) to form 4'-phospho-N-pantothenoylcysteine (PPC)
3. PPC is decarboxylated to 4'-phosphopantetheine by phosphopantothenoylcysteine decarboxylase (CoaC)
4. 4'-phosphopantetheine is adenylylated to form dephospho-CoA by the enzyme phosphopantetheine adenylyl transferase (CoaD)
5. Finally, dephospho-CoA is phosphorylated using ATP to coenzyme A by the enzyme dephosphocoenzyme A kinase (CoaE).

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.^[2][3]

List of coenzyme A activated acyl groups

• Acetyl-CoA
• Propionyl-CoA
• Acetoacetyl-CoA
• Coumaroyl-CoA (used in flavonoid and stilbenoid biosynthesis)
• 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)
  • 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)
• Benzoyl CoA
• Phenylacetyl CoA
• Butyryl CoA

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: 21431–21439. doi:10.1074/jbc.M201708200. PMID 11923312. 
2. ^ Elovson J, Vagelos PR (July 1968). "Acyl carrier protein. X. Acyl carrier protein synthetase". J. Biol. Chem. 243 (13): 3603–11. PMID 4872726. 
3. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2804320. 

Bibliography

• Karl Miller (1998). Beta Oxidation of Fatty Acids. Retrieved May 18, 2005.
• Charles Ophard (2003). Acetyl-CoA Crossroads. Retrieved May 18, 2005.
• Lehninger: Principles of Biochemistry, 4th edition, David L. Nelson, Michael M. Cox
• http://www.elmhurst.edu/~chm/vchembook/621fattyacidrx.html