Editing Coenzyme A (section)

==Biosynthesis==
Coenzyme A is naturally synthesized from [[Pantothenic acid|pantothenate]] (vitamin B<sub>5</sub>), which is found in food such as meat, vegetables, cereal grains, legumes, eggs, and milk.<ref>{{Cite web|url=http://www.umm.edu/health/medical/altmed/supplement/vitamin-b5-pantothenic-acid|title=Vitamin B<sub>5</sub> (Pantothenic acid)|website=University of Maryland Medical Center|language=en|access-date=2017-11-08|archive-date=2017-10-18|archive-url=https://web.archive.org/web/20171018192121/http://www.umm.edu/health/medical/altmed/supplement/vitamin-b5-pantothenic-acid|url-status=dead}}</ref> In humans and most living organisms, pantothenate is an essential vitamin that has a variety of functions.<ref>{{Cite web|url=https://medlineplus.gov/druginfo/natural/853.html|title=Pantothenic Acid (Vitamin B<sub>5</sub>): MedlinePlus Supplements|website=medlineplus.gov|language=en|access-date=2017-12-10|archive-date=2017-12-22|archive-url=https://web.archive.org/web/20171222155558/https://medlineplus.gov/druginfo/natural/853.html|url-status=dead}}</ref>&nbsp;In some plants and bacteria, including ''[[Escherichia coli]]'', pantothenate can be synthesised ''de novo'' and is therefore not considered essential. These bacteria synthesize pantothenate from the amino acid aspartate and a metabolite in valine biosynthesis.<ref name=":3">{{cite journal | vauthors = Leonardi R, Jackowski S | title = Biosynthesis of Pantothenic Acid and Coenzyme A | journal = EcoSal Plus | volume = 2 | issue = 2 | date = April 2007 | pmid = 26443589 | pmc = 4950986 | doi = 10.1128/ecosalplus.3.6.3.4 }}</ref>

In all living organisms, coenzyme A is synthesized in a five-step process that requires four molecules of ATP, pantothenate and cysteine<ref name=":4">{{cite journal | vauthors = Leonardi R, Zhang YM, Rock CO, Jackowski S | title = Coenzyme A: back in action | journal = Progress in Lipid Research | volume = 44 | issue = 2–3 | pages = 125–153 | year = 2005 | pmid = 15893380 | doi = 10.1016/j.plipres.2005.04.001 }}</ref> (see figure):
[[File:CoA_Biosynthetic_Pathway.png|thumb|Details of the biosynthetic pathway of CoA synthesis from pantothenic acid.]]
# [[Pantothenate]] (vitamin B<sub>5</sub>) is phosphorylated to 4′-phosphopantothenate by the enzyme [[pantothenate kinase]] (PanK; CoaA; CoaX). This is the committed step in CoA biosynthesis and requires ATP.<ref name=":3" />
# A [[cysteine]] is added to 4′-phosphopantothenate by the enzyme [[phosphopantothenoylcysteine synthetase]] (PPCS; CoaB) to form 4'-phospho-N-pantothenoylcysteine (PPC). This step is coupled with ATP hydrolysis.<ref name=":3" />
# PPC is decarboxylated to [[4'-phosphopantetheine|4′-phosphopantetheine]] by [[phosphopantothenoylcysteine decarboxylase]] (PPC-DC; CoaC)
# 4′-phosphopantetheine is adenylated (or more properly, [[Adenylation|AMPylated]]) to form dephospho-CoA by the enzyme [[Pantetheine-phosphate adenylyltransferase|phosphopantetheine adenylyl transferase]] (COASY; PPAT; CoaD)
# Finally, dephospho-CoA is phosphorylated to coenzyme A by the enzyme [[dephospho-CoA kinase|dephosphocoenzyme A kinase]] (COASY, DPCK; CoaE). This final step requires ATP.<ref name=":3" />
Enzyme nomenclature abbreviations in parentheses represent mammalian, other eukaryotic, and prokaryotic enzymes respectively. In mammals steps 4 and 5 are catalyzed by a bifunctional enzyme called [[COASY]].<ref name="Evers">{{cite journal | vauthors = Evers C, Seitz A, Assmann B, Opladen T, Karch S, Hinderhofer K, Granzow M, Paramasivam N, Eils R, Diessl N, Bartram CR, Moog U | display-authors = 6 | title = Diagnosis of CoPAN by whole exome sequencing: Waking up a sleeping tiger's eye | journal = American Journal of Medical Genetics. Part A | volume = 173 | issue = 7 | pages = 1878–1886 | date = July 2017 | pmid = 28489334 | doi = 10.1002/ajmg.a.38252 | s2cid = 27153945 }}</ref> This pathway is regulated by product inhibition. CoA is a competitive inhibitor for Pantothenate Kinase, which normally binds ATP.<ref name=":3" /> Coenzyme A, three ADP, one monophosphate, and one diphosphate are harvested from biosynthesis.<ref name=":4" />

Coenzyme A can be synthesized through alternate routes when intracellular coenzyme A level are reduced and the ''de novo'' pathway is impaired.<ref>{{cite journal | vauthors = de Villiers M, Strauss E | title = Metabolism: Jump-starting CoA biosynthesis | journal = Nature Chemical Biology | volume = 11 | issue = 10 | pages = 757–758 | date = October 2015 | pmid = 26379022 | doi = 10.1038/nchembio.1912 }}</ref> In these pathways, coenzyme A needs to be provided from an external source, such as food, in order to produce [[4'-phosphopantetheine|4′-phosphopantetheine]]. Ectonucleotide pyrophosphates (ENPP) degrade coenzyme A to 4′-phosphopantetheine, a stable molecule in organisms. [[Acyl carrier protein|Acyl carrier proteins (ACP)]] (such as ACP synthase and ACP degradation) are also used to produce 4′-phosphopantetheine. This pathway allows for 4′-phosphopantetheine to be replenished in the cell and allows for the conversion to coenzyme A through enzymes, PPAT and PPCK.<ref>{{cite journal | vauthors = Sibon OC, Strauss E | title = Coenzyme A: to make it or uptake it? | journal = Nature Reviews. Molecular Cell Biology | volume = 17 | issue = 10 | pages = 605–606 | date = October 2016 | pmid = 27552973 | doi = 10.1038/nrm.2016.110 | s2cid = 10344527 }}</ref>

A 2024 article<ref>{{cite journal |last1=Fairchild |first1=Jasper |last2=Islam |first2=Saidul |last3=Singh |first3=Jyoti |last4=Bučar |first4=Dejan-Krešimir |last5=Powner |first5=Matthew W. | title = Prebiotically plausible chemoselective pantetheine synthesis in water | journal = Science | volume = 383 | issue = 6685 | pages = 911-918 | date = 22 February 2024 | doi = 10.1126/science.adk4432 }}</ref> detailed a plausible chemical synthesis mechanism for the pantetheine component (the main functional part) of coenzyme A in a primordial [[Abiogenesis|prebiotic]] world.
===Commercial production===
Coenzyme A is produced commercially via extraction from yeast, however this is an inefficient process (yields approximately 25&nbsp;mg/kg) resulting in an expensive product. Various ways of producing CoA synthetically, or semi-synthetically have been investigated, although none are currently operating at an industrial scale.<ref>{{cite journal | vauthors = Mouterde LM, Stewart JD |title=Isolation and Synthesis of One of the Most Central Cofactors in Metabolism: Coenzyme A |journal=Organic Process Research & Development |volume=23 |pages=19–30 |date=19 December 2018 |doi=10.1021/acs.oprd.8b00348|s2cid=92802641 |url=https://hal.archives-ouvertes.fr/hal-02876007/file/Review%20final%205.0.pdf }}</ref>