Coenzyme A

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Coenzyme A
Coenzym A.svg
Coenzyme-A-3D-balls.png
Identifiers
CAS number 85-61-0 YesY
PubChem 6816
ChemSpider 6557 YesY
UNII SAA04E81UX YesY
DrugBank DB01992
KEGG C00010 YesY
MeSH Coenzyme+A
ChEBI CHEBI:15346 N
ChEMBL CHEMBL1213327 N
Jmol-3D images Image 1
Properties
Molecular formula C21H36N7O16P3S
Molar mass 767.535
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
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 cysteamine, pantothenate, and adenosine triphosphate (ATP).[1]

Biosynthesis[edit]

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 brackets 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]

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

Function[edit]

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[edit]

Additional images[edit]

References[edit]

  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[edit]