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Revision as of 19:56, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{chembox}} taken from revid 476124538 of page Acetyl-CoA for the Chem/Drugbox validation project (updated: '').		Latest revision as of 16:24, 13 December 2024 edit KMaster888 (talk | contribs)Extended confirmed users11,200 edits subjective ce
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			{{cs1 config|name-list-style=vanc}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}}
			{{Multiple issues|{{citation style|details=Multiple page-numbers in a single ref that is used multiple times: unclear which supports which<!--(use {{tl|rp}}?)-->. Some ISBN might be for wrong edition of the book. Need page-numbers for refs to whole broad-coverage textbooks. |date=August 2017}}
			{{Expert needed|biochemistry
			| date = August 2024
			| reason = Per ]: Needs more context about benzoyl-CoA and lactoyl-CoA. Some content needs to be moved to acyl-CoA article to fatty acyl-CoA.
			}}}}
	{{chembox		{{chembox
			| Verifiedfields = changed
	| verifiedrevid = 464364280
			| Watchedfields = changed
	| ImageFile = Acetyl-CoA-2D.svg
			| verifiedrevid = 477240040
			| Name = Acetyl-CoA
			| ImageFile = Acetyl-CoA-2D_colored.svg
			| ImageClass= skin-invert-image
	| ImageSize = 320		| ImageSize = 320
	| ImageFile2 = Acetyl-CoA-3D-balls.png		| ImageFile2 = Acetyl-CoA-3D-balls.png
	| ImageSize2 = 320		| ImageSize2 = 320
			| ImageFile3 = Acetyl-CoA-3D-vdW.png
	| IUPACName =
	| OtherNames =		| ImageSize3 = 320
			| PIN = ''O''<sup>1</sup>-<nowiki/>{(3''R'')-4-amino}-3-oxopropyl)amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl} ''O''<sup>3</sup>-<nowiki/>{methyl} dihydrogen diphosphate
			| OtherNames =
	| Section1 = {{Chembox Identifiers		| Section1 = {{Chembox Identifiers
			| IUPHAR_ligand = 3038
	| InChIKey = ZSLZBFCDCINBPY-ZSJPKINUBJ		| InChIKey = ZSLZBFCDCINBPY-ZSJPKINUBJ
	| InChI = 1/C23H38N7O17P3S/c1-12(31)51-7-6-25-14(32)4-5-26-21(35)18(34)23(2,3)9-44-50(41,42)47-49(39,40)43-8-13-17(46-48(36,37)38)16(33)22(45-13)30-11-29-15-19(24)27-10-28-20(15)30/h10-11,13,16-18,22,33-34H,4-9H2,1-3H3,(H,25,32)(H,26,35)(H,39,40)(H,41,42)(H2,24,27,28)(H2,36,37,38)/t13-,16-,17-,18+,22-/m1/s1		| InChI = 1/C23H38N7O17P3S/c1-12(31)51-7-6-25-14(32)4-5-26-21(35)18(34)23(2,3)9-44-50(41,42)47-49(39,40)43-8-13-17(46-48(36,37)38)16(33)22(45-13)30-11-29-15-19(24)27-10-28-20(15)30/h10-11,13,16-18,22,33-34H,4-9H2,1-3H3,(H,25,32)(H,26,35)(H,39,40)(H,41,42)(H2,24,27,28)(H2,36,37,38)/t13-,16-,17-,18+,22-/m1/s1
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	| StdInChIKey = ZSLZBFCDCINBPY-ZSJPKINUSA-N		| StdInChIKey = ZSLZBFCDCINBPY-ZSJPKINUSA-N
	| CASNo = 72-89-9		| CASNo = 72-89-9
	| CASNo_Ref = {{cascite|correct|CAS}}		| CASNo_Ref = {{cascite|correct|CAS}}
			| CASNo_Comment = (free acid)
			| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = 76Q83YLO3O
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID=392413		| ChemSpiderID=392413
	| PubChem = 444493		| PubChem = 444493
			| KEGG_Ref = {{keggcite|changed|kegg}}
			| KEGG = C00024
	| ChEBI_Ref = {{ebicite|correct|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 15351		| ChEBI = 15351
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	}}		}}
	| Section2 = {{Chembox Properties		| Section2 = {{Chembox Properties
			| C=23 | H=38 | N=7 | O=17 | P=3 | S=1
	| Formula = C<sub>23</sub>H<sub>38</sub>N<sub>7</sub>O<sub>17</sub>P<sub>3</sub>S
	| MolarMass = 809.57 g/mol
	| Appearance =		| Appearance =
	| Density =		| Density =
	| MeltingPt =		| MeltingPt =
	| BoilingPt =		| BoilingPt =
			| LambdaMax = 260 nm; 232 nm<ref name="lamda_source_1">{{cite book |last1=Dawson |first1=Rex M. C. |last2=Elliott |first2=Daphne C. |last3=Elliott |first3=William H. |last4=Jones |first4=Kenneth M. |title=Data for Biochemical Research |date=2002 |publisher=Clarendon Press |isbn=978-0-19-855299-4 |edition=3rd|page=117}}</ref>
			| Absorbance = ] = 16.4 mM<sup>−1</sup> cm<sup>−1</sup> (adenosine)<ref name="lamda_source_1" /><br /> ] = 8.7 mM<sup>−1</sup> cm<sup>−1</sup> (thioester)<ref name="lamda_source_1" /><br /> Δ] on thioester hydrolysis = −4.5 mM<sup>−1</sup> cm<sup>−1</sup><ref name="lamda_source_1" />
	}}		}}
	| Section3 = {{Chembox Hazards		| Section3 = {{Chembox Hazards
	| Solubility =
	| MainHazards =		| MainHazards =
	| FlashPt =		| FlashPt =
	| Autoignition =		| AutoignitionPt =
	}}		}}
			| Section4 =
			| Section5 =
			| Section6 =
	}}		}}
			'''Acetyl-CoA''' ('''acetyl coenzyme A''') is a molecule that participates in many ]s in protein, carbohydrate and lipid ].<ref>{{cite web|url=http://chemistry.elmhurst.edu/vchembook/623acetylCoAfate.html|title=Acetyl CoA Crossroads|website=chemistry.elmhurst.edu|access-date=2016-11-08|archive-date=2016-11-15|archive-url=https://web.archive.org/web/20161115202146/http://chemistry.elmhurst.edu/vchembook/623acetylCoAfate.html|url-status=dead}}</ref> Its main function is to deliver the ] group to the ] (Krebs cycle) to be ] for energy production.
			] (CoASH or CoA) consists of a ] linked to ] (vitamin B5) through an ]<ref>{{cite web|url=http://library.med.utah.edu/NetBiochem/FattyAcids/2_4.html|title=Fatty Acids -- Structure of Acetyl CoA|website=library.med.utah.edu|access-date=2017-06-02}}</ref> and 3'-phosphorylated ADP. The acetyl group (indicated in blue in the structural diagram on the right) of acetyl-CoA is linked to the ] substituent of the β-mercaptoethylamine group. This ] linkage is a "high energy" bond, which is particularly reactive. ] of the thioester bond is ] (−31.5&nbsp;kJ/mol).
			CoA is acetylated to acetyl-CoA by the breakdown of ] through ] and by the breakdown of ] through ]. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and water, and the energy released is captured in the form of 11 ] and one ] per acetyl group.
			] and ] were awarded the 1964 ] for their discoveries linking acetyl-CoA and fatty acid metabolism. ] won the Nobel Prize in 1953 for his discovery of the cofactor ].<ref>{{cite web |title=All Nobel Prizes in Physiology or Medicine |url=https://www.nobelprize.org/prizes/lists/all-nobel-laureates-in-physiology-or-medicine/ |website=The Nobel Prize}}</ref>
			== Role ==
			Acetyl-CoA is a ] that is involved in many metabolic pathways in an organism. It is produced during the breakdown of ], ], and ], and is used in the synthesis of many other ], including ], ]s, and ]. Acetyl-CoA is also a key molecule in the ], which is a series of chemical reactions that occur in the ] of cells and is responsible for generating energy in the form of ].<ref name="pmid31387584">{{cite journal |vauthors=Zhang S, Yang W, Chen H, Liu B, Lin B, Tao Y |title=Metabolic engineering for efficient supply of acetyl-CoA from different carbon sources in Escherichia coli |journal=Microb Cell Fact |volume=18 |issue=1 |pages=130 |date=August 2019 |pmid=31387584 |doi=10.1186/s12934-019-1177-y |pmc=6685171 |url= |doi-access=free }}</ref><ref>{{cite web | url=https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_%28Boundless%29/05%3A_Microbial_Metabolism/5.12%3A_Biosynthesis/5.12G%3A_The_Acetyl-CoA_Pathway | title=5.12G: The Acetyl-CoA Pathway | date=9 May 2017 }}</ref>
			In addition, acetyl-CoA is a precursor for the biosynthesis of various acetyl-chemicals, acting as an intermediate to transfer an acetyl group during the biosynthesis of those acetyl-chemicals. Acetyl-CoA is also involved in the regulation of various cellular mechanisms by providing acetyl groups to target amino acid residues for post-translational ] reactions of proteins.
			== Biosynthesis ==
			The acetylation of CoA is determined by the carbon sources.<ref>{{cite journal|last1=Hynes|first1=Michael J.|last2=Murray|first2=Sandra L.|date=2010-07-01|title=ATP-Citrate Lyase Is Required for Production of Cytosolic Acetyl Coenzyme A and Development in Aspergillus nidulans|journal=Eukaryotic Cell|language=en|volume=9|issue=7|pages=1039–1048|doi=10.1128/EC.00080-10|issn=1535-9778|pmc=2901662|pmid=20495057}}</ref><ref>{{cite journal|last1=Wellen|first1=Kathryn E.|last2=Thompson|first2=Craig B.|date=2012-04-01|title=A two-way street: reciprocal regulation of metabolism and signalling|journal=Nature Reviews Molecular Cell Biology|language=en|volume=13|issue=4|pages=270–276|doi=10.1038/nrm3305|issn=1471-0072|pmid=22395772|s2cid=244613}}</ref>
			=== Extramitochondrial ===
			At high ] levels, ] takes place rapidly, thus increasing the amount of ] produced from the ]. This citrate is then exported to other ]s outside the mitochondria to be broken into acetyl-CoA and ] by the ] ] (ACL). This principal reaction is coupled with the ] of ATP.<ref>{{cite book|url=https://books.google.com/books?id=d1nu4vcml8sC&q=reaction+of+ATP+citrate+lyase+produces+acetyl+coA&pg=PA253|title=Functional Metabolism: Regulation and Adaptation|last=Storey|first=Kenneth B.|date=2005-02-25|publisher=John Wiley & Sons|isbn=9780471675570|language=en}}</ref><ref>{{cite web|url=https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=47|title=ACLY ATP citrate lyase - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-11-06}}</ref>
			At low glucose levels CoA is acetylated using ] by ] (ACS), also coupled with ] hydrolysis.<ref>{{cite journal|last=Ragsdale|first=S. W.|title=Life with carbon monoxide|journal=CRC Critical Reviews in Biochemistry and Molecular Biology|date=2004|volume=39|issue=3|pages=165–195|doi=10.1080/10409230490496577|pmid=15596550|s2cid=16194968}}</ref> ] also serves as a carbon source for acetylation of CoA utilizing the enzyme ].<ref>{{cite book|url=https://books.google.com/books?id=xN0YYypnZVkC&q=reaction+of+Acetyl+CoA+synthase+produce+Acetyl+CoA&pg=PA275|title=Textbook of Biochemistry for Dental/Nursing/Pharmacy Students|last=Chatterjea|date=2004-01-01|publisher=Jaypee Brothers Publishers|isbn=9788180612046|language=en}}{{Dead link|date=February 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Degradation of branched-chain ] ]s such as ], ], and ] occurs. These amino acids are converted to α-ketoacids by ] and eventually to ] through oxidative decarboxylation by an α-ketoacid dehydrogenase complex. Isovaleryl-CoA undergoes ], ] and hydration to form another CoA-derivative intermediate before it is cleaved into acetyl-CoA and ].<ref name=":0">{{cite book|url=https://archive.org/details/biochemistrychap00jere|title=Biochemistry|last1=Berg|first1=Jeremy M.|last2=Tymoczko|first2=John L.|last3=Stryer|first3=Lubert|year=2002|publisher=W. H. Freeman|isbn=978-0716730514|edition=5th}}</ref>{{page needed|date=August 2017}}
			=== Intramitochondrial ===
			] complex reaction]]
			At high glucose levels, acetyl-CoA is produced through ].<ref>{{cite book|url=https://books.google.com/books?id=y8JQAwAAQBAJ&q=acetyl+coA+pathway&pg=PA149|title=Guide to Biochemistry|last=Blackstock|first=James C.|date=2014-06-28|publisher=Butterworth-Heinemann|isbn=9781483183671|language=en}}</ref> ] undergoes oxidative decarboxylation in which it loses its ] group (as ]) to form acetyl-CoA, giving off 33.5 kJ/mol of energy. The oxidative conversion of pyruvate into acetyl-CoA is referred to as the '''pyruvate dehydrogenase reaction'''. It is catalyzed by the ]. Other conversions between pyruvate and acetyl-CoA are possible. For example, ] ] pyruvate into acetyl-CoA and ].
			] of ]s]]
			At low glucose levels, the production of acetyl-CoA is linked to ] of ]s. Fatty acids are first converted to acyl-CoA. Acyl-CoA is then degraded in a four-step cycle of ], ], ] and ] catalyzed by four respective enzymes, namely ], ], ], and ]. The cycle produces a new fatty acid chain with two fewer carbons and acetyl-CoA as a byproduct.<ref>{{cite journal|last1=Houten|first1=Sander Michel|last2=Wanders|first2=Ronald J. A.|date=2010-03-02|title=A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation|journal=Journal of Inherited Metabolic Disease|language=en|volume=33|issue=5|pages=469–477|doi=10.1007/s10545-010-9061-2|issn=0141-8955|pmc=2950079|pmid=20195903}}</ref>
			==Functions==
			=== Intermediates in various pathways ===
			* In ]
			* ]:
			** Through a series of chemical reactions, stored energy is released through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins into ] (ATP) and ].
			* ]
			** Acetyl-CoA is produced by the breakdown of both ]s (by ]) and ] (by ]). It then enters the citric acid cycle in the mitochondrion by combining with ] to form ].<ref name="stryer2">{{cite book |last1= Stryer |first1= Lubert | title=Biochemistry. | edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 510–515, 559–565, 581–613, 614–623, 775–778 |isbn= 978-0-7167-2009-6 }}</ref><ref name="oxidation_of_fats">{{cite web|url=http://pharmaxchange.info/press/2013/10/oxidation-of-fatty-acids/|title=Oxidation of fatty acids|date=2013-10-11}}</ref>
			** Two acetyl-CoA molecules condense to form ], which gives rise to the formation of ] and ].<ref name="stryer2" /> Acetoacetate, β-hydroxybutyrate, and their spontaneous breakdown product ]<ref>{{cite web|url=http://watcut.uwaterloo.ca/webnotes/Metabolism/fatKetoneBodyMetabolism.html|title=Ketone body metabolism|publisher=University of Waterloo}}</ref> are frequently, but confusingly, known as ] (as they are not "bodies" at all, but water-soluble chemical substances). The ketone bodies are released by the ] into the blood. All cells with mitochondria can take ketone bodies up from the blood and reconvert them into acetyl-CoA, which can then be used as fuel in their citric acid cycles, as no other tissue can divert its oxaloacetate into the ] in the way that the liver does. Unlike free fatty acids, ketone bodies can cross the ] and are therefore available as fuel for the cells of the ], acting as a substitute for glucose, on which these cells normally survive.<ref name="stryer2" /> The occurrence of high levels of ketone bodies in the blood during ], a ], prolonged heavy exercise, and uncontrolled ] is known as ], and in its extreme form in out-of-control type-1 diabetes mellitus, as ].
			** On the other hand, when the ] concentration in the blood is high, and that of ] is low (i.e. after meals), the acetyl-CoA produced by glycolysis condenses as normal with oxaloacetate to form citrate in the mitochondrion. However, instead of continuing through the citric acid cycle to be converted to carbon dioxide and water, the citrate is removed from the mitochondrion into the ].<ref name="stryer2" /> There it is cleaved by ] into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to the mitochondrion as malate (and then converted back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion).<ref name="ferre">{{cite journal | doi = 10.1159/000100426 | title = SREBP-1c Transcription Factor and Lipid Homeostasis: Clinical Perspective | journal = Hormone Research | year = 2007 | first = P. | last = Ferre |author2=F. Foufelle | volume = 68 | issue = 2 | pages = 72–82| doi-broken-date = 2 December 2024 | pmid = 17344645 | quote = this process is outlined graphically in page 73| doi-access = free }}</ref> This cytosolic acetyl-CoA can then be used to synthesize fatty acids through carboxylation by ] into ], the first committed step in the synthesis of fatty acids.<ref name="ferre" /><ref name="Voet">{{cite book |last=Voet |first=Donald |author2=Judith G. Voet |author3=Charlotte W. Pratt |title=Fundamentals of Biochemistry, 2nd Edition |publisher=John Wiley and Sons, Inc. |year=2006 |pages= |isbn=978-0-471-21495-3 |url=https://archive.org/details/fundamentalsofbi00voet_0/page/547 }}</ref> This conversion occurs primarily in the liver, ] and lactating ]s, where the fatty acids are combined with ] to form ]s, the major fuel reservoir of most animals. Fatty acids are also components of the ]s that make up the bulk of the ]s of all ]s.<ref name="stryer2" />
			** In plants, ''de novo'' fatty acid synthesis occurs in the ]s. Many ]s accumulate large reservoirs of seed oils to support ] and early growth of the seedling before it is a net ] organism.
			** The ]ic acetyl-CoA can also condense with ] to form 3-hydroxy-3-methylglutaryl-CoA (]) which is the rate-limiting step controlling the ].<ref name="stryer2" /> ] can be used as is, as a structural component of cellular membranes, or it can be used to synthesize ], ], and ].<ref name="stryer2" /><ref name="Voet" />
			** Acetyl-CoA can be ] in the cytosol by ], giving rise to ], a substrate required for synthesis of ]s and related ]s, for elongation of fatty acids to produce ]es, ], and seed oils in members of the ] family, and for ] of proteins and other phytochemicals.<ref>{{cite journal|year=2005|title=Reverse Genetic Characterization of Cytosolic Acetyl-CoA Generation by ATP-Citrate Lyase in Arabidopsis|journal=The Plant Cell Online|volume=17|issue=1|pages=182–203|doi=10.1105/tpc.104.026211|pmid=15608338|last1=Fatland|first1=B. L.|pmc=544498|bibcode=2005PlanC..17..182F }}</ref> In plants, these include ]s, ]s (hormones), and membrane ]s.
			* ]:
			** Acetyl-CoA participates in the ] by partaking in the synthesis of hydroxymethyl glutaryl-CoA.
			* ] synthesis:
			** Acetyl-CoA is also an important component in the biogenic synthesis of the ] ]. ], in combination with acetyl-CoA, is catalyzed by the enzyme ] to produce acetylcholine and ] as a byproduct.
			* ] synthesis
			* Acetylation
			** Acetyl-CoA is also the source of the acetyl group incorporated onto certain ] residues of ] and nonhistone proteins in the ] ]. This acetylation is catalyzed by ]. This acetylation affects ], ], and ].<ref>{{cite journal|last1=Yi|first1=C. H.|last2=Vakifahmetoglu-Norberg|first2=H.|last3=Yuan|first3=J.|date=2011-01-01|title=Integration of Apoptosis and Metabolism|journal=Cold Spring Harbor Symposia on Quantitative Biology|language=en|volume=76|pages=375–387|doi=10.1101/sqb.2011.76.010777|issn=0091-7451|pmid=22089928|doi-access=free}}</ref>
			*Allosteric regulator
			** Acetyl-CoA serves as an ] of ] (PDK). It regulates through the ratio of acetyl-CoA versus CoA. Increased concentration of acetyl-CoA activates PDK.<ref>{{cite journal|last1=Pettit|first1=Flora H.|last2=Pelley|first2=John W.|last3=Reed|first3=Lester J.|date=1975-07-22|title=Regulation of pyruvate dehydrogenase kinase and phosphatase by acetyl-CoA/CoA and NADH/NAD ratios|journal=Biochemical and Biophysical Research Communications|volume=65|issue=2|pages=575–582|doi=10.1016/S0006-291X(75)80185-9|pmid=167775}}</ref>
			** Acetyl-CoA is also an allosteric activator of ].<ref>{{cite journal|last1=Jitrapakdee|first1=Sarawut|last2=Maurice|first2=Martin St.|author3-link=Ivan Rayment|last3=Rayment|first3=Ivan|last4=Cleland|first4=W. Wallace|last5=Wallace|first5=John C.|last6=Attwood|first6=Paul V.|date=2008-08-01|title=Structure, Mechanism and Regulation of Pyruvate Carboxylase|journal=The Biochemical Journal|volume=413|issue=3|pages=369–387|doi=10.1042/BJ20080709|issn=0264-6021|pmc=2859305|pmid=18613815}}</ref>
			==Interactive pathway map==
			''Click on genes, proteins and metabolites below to visit ] pages and related Misplaced Pages articles. The pathway can be downloaded and edited at .''
			{| style="margin-left: auto; margin-right: auto; border: none;"
			| width="390px"|{{TCACycle_WP78|highlight=Acetyl-CoA|header=}}
			| width="390px"|{{StatinPathway_WP430|highlight=Acetyl-coa|header=}}
			|}
			==See also==
			* ]
			==References==
			{{reflist}}
			==External links==
			* {{MeshName|Acetyl+Coenzyme+A}}
			{{Fatty-acid metabolism intermediates}}
			{{Cholesterol metabolism intermediates}}
			{{Glycolysis}}
			{{Citric acid cycle}}
			{{Amino acid metabolism intermediates}}
			{{Acetylcholine receptor modulators}}
			{{Authority control}}
			{{DEFAULTSORT:Acetyl-Coa}}
			]
			]
			]
			]
			]
			]