Editing Coenzyme A (section)

== Function ==

=== Fatty acid synthesis ===

Since coenzyme A is, in chemical terms, a [[thiol]], it can react with [[carboxylic acid]]s to form [[thioester]]s, thus functioning as an [[acyl]] group carrier. It assists in transferring [[fatty acid]]s from the [[cytoplasm]] to [[mitochondria]].  A molecule of coenzyme A carrying an [[acyl group]] is also referred to as ''[[acyl-CoA]]''. When it is not attached to an acyl group, it is usually referred to as 'CoASH' or 'HSCoA'. This process facilitates the production of fatty acids in cells, which are essential in cell membrane structure.

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]].<ref>{{cite journal | vauthors = Elovson J, Vagelos PR | title = Acyl carrier protein. X. Acyl carrier protein synthetase | journal = The Journal of Biological Chemistry | volume = 243 | issue = 13 | pages = 3603–3611 | date = July 1968 | pmid = 4872726 | doi = 10.1016/S0021-9258(19)34183-3 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Strickland KC, Hoeferlin LA, Oleinik NV, Krupenko NI, Krupenko SA | title = Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase | journal = The Journal of Biological Chemistry | volume = 285 | issue = 3 | pages = 1627–1633 | date = January 2010 | pmid = 19933275 | pmc = 2804320 | doi = 10.1074/jbc.M109.080556 | doi-access = free }}</ref>[[File:CoA_Sources_and_Uses.png|thumb|Some of the sources that CoA comes from and uses in the cell.]]

=== Energy production ===

Coenzyme A is one of five crucial coenzymes that are necessary in the reaction mechanism of the [[citric acid cycle]]. Its acetyl-coenzyme A form is the primary input in the citric acid cycle and is obtained from [[glycolysis]], amino acid metabolism, and fatty acid beta oxidation. This process is the body's primary [[Catabolism|catabolic pathway]] and is essential in breaking down the building blocks of the cell such as [[carbohydrate]]s, [[amino acid]]s, and [[lipid]]s.<ref>{{Cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |date=2002|title=Molecular Biology of the Cell | edition = 4th | chapter = Chapter 2: How Cells Obtain Energy from Food|publisher=Garland Science | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK26882/|language=en}}</ref>

=== Regulation ===
When there is excess glucose, coenzyme A is used in the cytosol for synthesis of fatty acids.<ref name=":2">{{cite journal | vauthors = Shi L, Tu BP | title = Acetyl-CoA and the regulation of metabolism: mechanisms and consequences | journal = Current Opinion in Cell Biology | volume = 33 | pages = 125–131 | date = April 2015 | pmid = 25703630 | pmc = 4380630 | doi = 10.1016/j.ceb.2015.02.003 }}</ref> This process is implemented by regulation of [[acetyl-CoA carboxylase]], which catalyzes the committed step in fatty acid synthesis. [[Insulin]] stimulates acetyl-CoA carboxylase, while [[epinephrine]] and [[glucagon]] inhibit its activity.<ref>{{Cite book | vauthors = Berg JM, Tymoczko JL, Stryer L |date=2002 | title = Biochemistry | chapter = Acetyl Coenzyme A Carboxylase Plays a Key Role in Controlling Fatty Acid Metabolism| chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK22381/|language=en}}</ref>

During cell starvation, coenzyme A is synthesized and transports fatty acids in the cytosol to the mitochondria. Here, acetyl-CoA is generated for oxidation and energy production.<ref name=":2" /> In the citric acid cycle, coenzyme A works as an allosteric regulator in the stimulation of the enzyme [[pyruvate dehydrogenase]].

=== Antioxidant function and regulation ===
Discovery of the novel antioxidant function of coenzyme A highlights its protective role during cellular stress. Mammalian and bacterial cells subjected to oxidative and metabolic stress show significant increase in the covalent modification of protein cysteine residues by coenzyme A.<ref>{{cite journal | vauthors = Tsuchiya Y, Peak-Chew SY, Newell C, Miller-Aidoo S, Mangal S, Zhyvoloup A, Bakovic J, Malanchuk O, Pereira GC, Kotiadis V, Szabadkai G, Duchen MR, Campbell M, Cuenca SR, Vidal-Puig A, James AM, Murphy MP, Filonenko V, Skehel M, Gout I | display-authors = 6 | title = Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells | journal = The Biochemical Journal | volume = 474 | issue = 14 | pages = 2489–2508 | date = July 2017 | pmid = 28341808 | pmc = 5509381 | doi = 10.1042/BCJ20170129 }}</ref><ref name="Tsuchiya 1909–1937">{{cite journal | vauthors = Tsuchiya Y, Zhyvoloup A, Baković J, Thomas N, Yu BY, Das S, Orengo C, Newell C, Ward J, Saladino G, Comitani F, Gervasio FL, Malanchuk OM, Khoruzhenko AI, Filonenko V, Peak-Chew SY, Skehel M, Gout I | display-authors = 6 | title = Protein CoAlation and antioxidant function of coenzyme A in prokaryotic cells | journal = The Biochemical Journal | volume = 475 | issue = 11 | pages = 1909–1937 | date = June 2018 | pmid = 29626155 | pmc = 5989533 | doi = 10.1042/BCJ20180043 }}</ref> This reversible modification is termed protein CoAlation (Protein-S-SCoA), which plays a similar role to [[S-Glutathionylation|protein ''S''-glutathionylation]] by preventing the irreversible oxidation of the [[Thiol|thiol group]] of cysteine residues.

Using anti-coenzyme A antibody<ref>{{Cite journal | vauthors = Malanchuk OM, Panasyuk GG, Serbyn NM, Gout IT, Filonenko VV |date=2015 |title=Generation and characterization of monoclonal antibodies specific to Coenzyme A |url=http://biopolymers.org.ua/content/31/3/187/ |journal=Biopolymers and Cell |language=EN |volume=31 |issue=3 |pages=187–192 |doi=10.7124/bc.0008DF |issn=0233-7657|doi-access=free }}</ref> and liquid chromatography tandem mass spectrometry ([[Liquid chromatography–mass spectrometry|LC-MS/MS]]) methodologies, more than 2,000 CoAlated proteins were identified from stressed mammalian and bacterial cells.<ref name=":1">{{cite journal | vauthors = Tossounian MA, Baczynska M, Dalton W, Newell C, Ma Y, Das S, Semelak JA, Estrin DA, Filonenko V, Trujillo M, Peak-Chew SY, Skehel M, Fraternali F, Orengo C, Gout I | display-authors = 6 | title = Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions | journal = Antioxidants | volume = 11 | issue = 7 | pages = 1362 | date = July 2022 | pmid = 35883853 | pmc = 9312308 | doi = 10.3390/antiox11071362 | doi-access = free }}</ref>  The majority of these proteins are involved in cellular metabolism and stress response.<ref name=":1" /> Different research studies have focused on deciphering the coenzyme A-mediated regulation of proteins. Upon protein CoAlation, inhibition of the catalytic activity of different proteins (e.g., metastasis suppressor [[NME1]], [[PRDX5|peroxiredoxin 5]], [[Glyceraldehyde 3-phosphate dehydrogenase|GAPDH]], among others) is reported.<ref>{{cite journal | vauthors = Tossounian MA, Zhang B, Gout I | title = The Writers, Readers, and Erasers in Redox Regulation of GAPDH | journal = Antioxidants | volume = 9 | issue = 12 | pages = 1288 | date = December 2020 | pmid = 33339386 | pmc = 7765867 | doi = 10.3390/antiox9121288 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yu BY, Tossounian MA, Hristov SD, Lawrence R, Arora P, Tsuchiya Y, Peak-Chew SY, Filonenko V, Oxenford S, Angell R, Gouge J, Skehel M, Gout I | display-authors = 6 | title = Regulation of metastasis suppressor NME1 by a key metabolic cofactor coenzyme A | journal = Redox Biology | volume = 44 | pages = 101978 | date = August 2021 | pmid = 33903070 | pmc = 8212152 | doi = 10.1016/j.redox.2021.101978 }}</ref><ref name="Tsuchiya 1909–1937"/><ref>{{cite journal | vauthors = Baković J, Yu BY, Silva D, Chew SP, Kim S, Ahn SH, Palmer L, Aloum L, Stanzani G, Malanchuk O, Duchen MR, Singer M, Filonenko V, Lee TH, Skehel M, Gout I | display-authors = 6 | title = A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification | journal = Molecular and Cellular Biochemistry | volume = 461 | issue = 1–2 | pages = 91–102 | date = November 2019 | pmid = 31375973 | pmc = 6790197 | doi = 10.1007/s11010-019-03593-w }}</ref> To restore the protein's activity, antioxidant enzymes that reduce the disulfide bond between coenzyme A and the protein cysteine residue play an important role. This process is termed protein deCoAlation. Thioredoxin A and Thioredoxin-like protein (YtpP), two bacterial proteins, are shown to deCoAlate proteins.<ref>{{cite journal | vauthors = Tossounian MA, Baczynska M, Dalton W, Peak-Chew SY, Undzenas K, Korza G, Filonenko V, Skehel M, Setlow P, Gout I | display-authors = 6 | title = ''Bacillus subtilis'' YtpP and Thioredoxin A Are New Players in the Coenzyme-A-Mediated Defense Mechanism against Cellular Stress | journal = Antioxidants | volume = 12 | issue = 4 | pages = 938 | date = April 2023 | pmid = 37107313 | pmc = 10136147 | doi = 10.3390/antiox12040938 | doi-access = free }}</ref>