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'''아세틸 조효소 A'''({{llang|en|acetyl coenzyme A}}) 또는 '''아세틸-CoA'''({{llang|en|acetyl-CoA}})는 [[단백질]], [[탄수화물]] 및 [[지질 (생물학)|지질]] 대사 등 많은 생화학 반응에 참여하는 분자이다. 아세틸-CoA의 주요 기능은 아세틸기를 [[시트르산 회로]]에 전달하여 에너지 생산을 위해 산화되도록 하는 것이다. 조효소 A(CoA-SH 또는 CoA)에서 [[판토텐산]]의 [[하이드록시기]]는 3′-포스포아데노신 이인산과 인산에스터(인산에스테르) 결합을 하고 있으며, 판토텐산의 [[카복실기]]는 β-메르캅토에틸아민과 아마이드 결합을 하고 있다. 아세틸-CoA의 아세틸기(오른쪽 구조식에서 파란색으로 표시)는 β-메르캅토에틸아민 부분의 -SH기와 티오에스터(티오에스테르) 결합을 형성한다. 이러한 티오에스터(티오에스테르) 결합은 특히 반응성이 강한 "고에너지" 결합이다. 티오에스터(티오에스테르) 결합의 가수분해는 발열 반응()이다.'''Acetyl-CoA''' ('''acetyl coenzyme A''') is a molecule that participates in many [[biochemical reaction]]s in protein, carbohydrate and lipid [[metabolism]].<ref>{{Cite web|url=http://chemistry.elmhurst.edu/vchembook/623acetylCoAfate.html|title=Acetyl CoA Crossroads|website=chemistry.elmhurst.edu|access-date=2016-11-08}}</ref> Its main function is to deliver the [[acetyl]] group to the [[citric acid cycle]] (Krebs cycle) to be [[oxidation|oxidized]] for energy production. [[Coenzyme A]] (CoASH or CoA) consists of a [[cysteamine|β-mercaptoethylamine group]] linked to the vitamin [[pantothenic acid]] through an [[amide linkage]] <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 [[sulfhydryl]] substituent of the β-mercaptoethylamine group. This [[thioester]] linkage is a "high energy" bond, which is particularly reactive. [[Hydrolysis]] of the thioester bond is [[exergonic]] (−31.5&nbsp;kJ/mol).<!-- compare with hydrolysis of normal ester?-->
'''아세틸 조효소 A'''({{llang|en|acetyl coenzyme A}}) 또는 '''아세틸-CoA'''({{llang|en|acetyl-CoA}})는 [[단백질]], [[탄수화물]] 및 [[지질 (생물학)|지질]] 대사 등 많은 생화학 반응에 참여하는 분자이다. '''CoA''','''SCoA''','''CoASH''') is a [[coenzyme]], notable for its role in the [[Fatty acid metabolism#Synthesis|synthesis]] and [[Fatty acid metabolism#.CE.B2-Oxidation|oxidation]] of [[fatty acid]]s, and the oxidation of [[pyruvic acid|pyruvate]] in the [[citric acid cycle]]. All [[genome]]s 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 [[cysteine]], [[pantothenic acid|pantothenate]], and [[adenosine triphosphate]] (ATP).<ref>{{cite journal |title=Complete Reconstitution of the Human Coenzyme A Biosynthetic Pathway via Comparative Genomics |author1=Matthew Daugherty |author2=Boris Polanuyer |author3=Michael Farrell |author4=Michael Scholle |author5=Athanasios Lykidis |author6=Valérie de Crécy-Lagard |author7=Andrei Osterman |year=2002 |doi=10.1074/jbc.M201708200 |journal=The Journal of Biological Chemistry |volume=277 |pages=21431–21439 |pmid=11923312 |issue=24}}</ref>


CoA is acetylated to acetyl-CoA by the breakdown of [[carbohydrates]] through [[glycolysis]] and by the breakdown of [[fatty acids]] through [[Beta oxidation|β-oxidation]]. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and water, and the energy released captured in the form of 11 [[Adenosine triphosphate|ATP]] and one [[Guanosine triphosphate|GTP]] per acetyl group.
==Discovery of structure==
[[File:Coenzym A beschriftet.svg|thumb|300 px|Structure of coenzyme A: 1: 3'-phosphoadenosine. 2: diphosphate, organophosphate anhydride. 3: pantoic acid. 4: β-alanine. 5: β-cystamine.]]
The structure of coenzyme A was identified in the early 1950s at the [[Lister Institute]], London, together by Fritz Lipmann and other workers at [[Harvard Medical School]] and [[Massachusetts General Hospital]].<ref name="Nature">{{cite journal|last=Baddiley|first=J.|last2=Thain|first2=E. M.|last3=Novelli|first3=G. D.|last4=Lipmann|first4=F.|year=1953|title=Structure of Coenzyme A|journal=[[Nature (journal)|Nature]]|volume=171|issue=4341|pages=76|doi=10.1038/171076a0}}</ref> Lipmann initially intended to study acetyl transfer in animals, and from these experiments he noticed a unique factor that was not present in enzyme extracts but was evident in all organs of the animals. He was able to isolate and purify the factor from pig liver and discovered that its function was related to a coenzyme that was active in choline acetylation.<ref name=":0">{{Cite journal|last=Kresge|first=Nicole|last2=Simoni|first2=Robert D.|last3=Hill|first3=Robert L.|date=2005-05-27|title=Fritz Lipmann and the Discovery of Coenzyme A|url=http://www.jbc.org/content/280/21/e18|journal=Journal of Biological Chemistry|language=en|volume=280|issue=21|pages=e18–e18|issn=0021-9258}}</ref> The coenzyme was named coenzyme A to stand for "activation of acetate". In 1953, Fritz Lipmann won the Nobel Prize in Physiology or Medicine "for his discovery of co-enzyme A and its importance for intermediary metabolism".<ref name=":0" /><ref>"Fritz Lipmann - Facts".&nbsp;Nobelprize.org.&nbsp;Nobel Media AB 2014. Web. 8 Nov 2017. <<nowiki>http://www.nobelprize.org/nobel_prizes/medicine/laureates/1953/lipmann-facts.html</nowiki>></ref>


[[Konrad Bloch]] and [[Feodor Lynen]] were awarded the 1964 [[Nobel Prize in Physiology and Medicine]] for their discoveries linking acetyl-CoA and fatty acid metabolism. [[Fritz Lipmann]] won the Nobel Prize in 1953 for his discovery of the cofactor [[coenzyme A]].
==Biosynthesis==
Coenzyme A is naturally synthesized from pantothenate (vitamin B5), 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 B5 (Pantothenic acid)|website=University of Maryland Medical Center|language=en|access-date=2017-11-08}}</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 B5): MedlinePlus Supplements|website=medlineplus.gov|language=en|access-date=2017-12-10}}</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|last=LEONARDI|first=ROBERTA|last2=JACKOWSKI|first2=SUZANNE|date=April 2007|title=Biosynthesis of Pantothenic Acid and Coenzyme A|journal=EcoSal Plus|volume=2|issue=2|doi=10.1128/ecosalplus.3.6.3.4|issn=2324-6200|pmc=4950986|pmid=26443589}}</ref>


== Direct synthesis ==
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 |title=Coenzyme A: back in action |vauthors=Leonardi R, Zhang YM, Rock CO, Jackowski S |year=2005 |doi=10.1016/j.plipres.2005.04.001 |journal=Progress in Lipid Research |volume=44 |pages=125–153 |pmid=15893380 |issue=2-3}}</ref> (see Figure)[[File:CoA_Biosynthetic_Pathway.png|thumb|Details the biosynthetic pathway of CoA synthesis from pantothenic acid.]]
The acetylation of CoA is determined by the carbon sources.<ref>{{Cite journal|last=Hynes|first=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|url=http://ec.asm.org/content/9/7/1039|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|last=Wellen|first=Kathryn E.|last2=Thompson|first2=Craig B.|date=2012-04-01|title=A two-way street: reciprocal regulation of metabolism and signalling|url=http://www.nature.com/nrm/journal/v13/n4/full/nrm3305.html|journal=Nature Reviews Molecular Cell Biology|language=en|volume=13|issue=4|pages=270–276|doi=10.1038/nrm3305|issn=1471-0072|pmid=22395772}}</ref>
# [[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]] by [[phosphopantothenoylcysteine decarboxylase]] (PPC-DC; CoaC)
# [[4'-phosphopantetheine]] is adenylylated (or more properly, [[Adenylation|AMPylated]]) to form dephospho-CoA by the enzyme [[Pantetheine-phosphate adenylyltransferase|phosphopantetheine adenylyl transferase]] (PPAT; CoaD)
# Finally, dephospho-CoA is phosphorylated to coenzyme A by the enzyme [[dephospho-CoA kinase|dephosphocoenzyme A kinase]] (DPCK; CoaE). This final step requires ATP.<ref name=":3" />
Enzyme nomenclature abbreviations in parentheses represent eukaryotic and prokaryotic enzymes respectively. 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" />


=== Extramitochondrial ===
New research shows that 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|last=de Villiers|first=Marianne|last2=Strauss|first2=Erick|date=October 2015|title=Metabolism: Jump-starting CoA biosynthesis|journal=Nature Chemical Biology|volume=11|issue=10|pages=757–758|doi=10.1038/nchembio.1912|issn=1552-4469|pmid=26379022}}</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 pathways 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|last=Sibon|first=Ody C. M.|last2=Strauss|first2=Erick|date=October 2016|title=Coenzyme A: to make it or uptake it?|journal=Nature Reviews. Molecular Cell Biology|volume=17|issue=10|pages=605–606|doi=10.1038/nrm.2016.110|issn=1471-0080|pmid=27552973}}</ref>
* At high [[glucose]] levels, [[glycolysis]] takes place rapidly, thus increasing the amount of [[citrate]] produced from the tricarboxylic acid cycle. This citrate is then exported to other [[organelle]]s outside the mitochondria to be broken into acetyl-CoA and [[oxaloacetate]] by the [[enzyme]] [[ATP citrate lyase]] (ACL). This principal reaction is coupled with the hydrolysis of ATP.<ref>{{Cite book|url=https://books.google.com/?id=d1nu4vcml8sC&pg=PA253&dq=reaction+of+ATP+citrate+lyase+produces+acetyl+coA#v=onepage&q=reaction%20of%20ATP%20citrate%20lyase%20produces%20acetyl%20coA&f=false|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 [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-11-06}}</ref>
* At low glucose levels:
** CoA is acetylated using [[acetate]] by [[acetyl-CoA synthetase]] (ACS), also coupled with [[adenosine triphosphate|ATP]] 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|pages=165–195}}</ref>
** [[Ethanol]] also serves as a carbon source for acetylation of CoA utilizing the enzyme [[alcohol dehydrogenase]].<ref>{{Cite book|url=https://books.google.com/?id=xN0YYypnZVkC&pg=PA275&dq=reaction+of+Acetyl+CoA+synthase+produce+Acetyl+CoA#v=onepage&q=reaction%20of%20Acetyl%20CoA%20synthase%20produce%20Acetyl%20CoA&f=false|title=Textbook of Biochemistry for Dental/Nursing/Pharmacy Students|last=Chatterjea|date=2004-01-01|publisher=Jaypee Brothers Publishers|isbn=9788180612046|language=en}}</ref>
** Degradation of branched-chain [[ketogenic]] [[amino acid]]s such as [[valine]], [[leucine]], and [[isoleucine]] occurs. These amino acids are converted to α-ketoacids by [[transamination]] and eventually to isovaleryl-CoA through oxidative decarboxylation by an α-ketoacid dehydrogenase complex. Isovaleryl-CoA undergoes [[dehydrogenation]], [[carboxylation]] and hydration to form another CoA-derivative intermediate before it is cleaved into acetyl-CoA and [[acetoacetate]].<ref name=":0">{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK21154/|title=Biochemistry|last=Berg|first=Jeremy M.|last2=Tymoczko|first2=John L.|last3=Stryer|first3=Lubert|year=2002|publisher=W. H. Freeman|isbn=0716730510|edition=5th}}</ref>{{page needed|date=August 2017}}


=== Intramitochondrial ===
==Function==
[[File:Pyruvate dehydrogenase complex reaction.PNG|left|thumb|[[Pyruvate dehydrogenase]] complex reaction]]
* At high glucose levels, acetyl-CoA is produced through [[glycolysis]].<ref>{{Cite book|url=https://books.google.com/?id=y8JQAwAAQBAJ&pg=PA149&dq=acetyl+coA+pathway#v=onepage&q=acetyl%20coA%20pathway&f=false|title=Guide to Biochemistry|last=Blackstock|first=James C.|date=2014-06-28|publisher=Butterworth-Heinemann|isbn=9781483183671|language=en}}</ref> [[Pyruvate]] undergoes oxidative decarboxylation in which it loses its [[carboxyl]] group (as [[carbon dioxide]]) to form acetyl-CoA, giving off 33.5&nbsp;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 [[pyruvate dehydrogenase complex]]. Other conversions between pyruvate and acetyl-CoA are possible. For example, [[pyruvate formate lyase]] disproportionates pyruvate into acetyl-CoA and [[formic acid]].
[[File:Metabolism4.jpg|right|thumb|282px|[[beta-oxidation|β-Oxidation]] of [[fatty acid]]s]]
* At low glucose levels, the production of acetyl-CoA is linked to [[beta oxidation|β-oxidation]] of [[fatty acid]]s. Fatty acids are first converted to acyl-CoA. Acyl-CoA is then degraded in a four-step cycle of dehydrogenation, hydration, oxidation and [[thiolysis]] catalyzed by four respective enzymes, namely [[acyl-CoA dehydrogenase]], [[enoyl-CoA hydratase]], [[3-hydroxyacyl-CoA dehydrogenase]], and [[thiolase]]. The cycle produces a new acyl-CoA with two fewer carbons and acetyl-CoA as a byproduct.<ref>{{Cite journal|last=Houten|first=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|url=https://link.springer.com/article/10.1007/s10545-010-9061-2|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==
=== Fatty acid synthesis ===


=== Intermediates in various pathways ===
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 [[acetyl]] 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.<ref name=":1" />
* In Cellular Respiration
* Citric acid cycle:
** Acetyl-CoA reacts with [[oxaloacetate]] to form [[citrate]], which is then oxidized to [[carbon dioxide|CO<sub>2</sub>]] in the cycle.<ref name=":0" />{{page needed|date=August 2017}}
* [[Fatty acid metabolism]]
** Acetyl-CoA is produced by the breakdown of both [[carbohydrate]]s (by [[glycolysis]]) and [[lipids]] (by [[Beta oxidation|β-oxidation]]). It then enters the citric acid cycle in the mitochondrion by combining with [[Oxaloacetic acid|oxaloacetate]] to form [[citric acid|citrate]].<ref name="stryer2">{{cite book |last1= Stryer |first1= Lubert | title=Biochemistry. | edition= Fourth |location= New York |publisher= W.H. Freeman and Company|publication-date= 1995 |pages= 510–515, 559–565, 581–613, 614–623, 775–778 |isbn= 0-7167-2009-4 }}</ref><ref name="oxidation_of_fats">{{cite web|url=http://pharmaxchange.info/press/2013/10/oxidation-of-fatty-acids/|title=Oxidation of fatty acids}}</ref>
** Two acetyl-CoA molecules condense to form [[acetoacetyl-CoA]], which gives rise to the formation of [[Acetoacetic acid|acetoacetate]] and [[beta-Hydroxybutyric acid|β-hydroxybutyrate]].<ref name="stryer2" /> Acetoacetate, β-hydroxybutyrate, and their spontaneous breakdown product [[acetone]]<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 [[ketone bodies]] (as they are not "bodies" at all, but water-soluble chemical substances). The ketone bodies are released by the [[liver]] 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 [[gluconeogenesis|gluconeogenic pathway]] in the way that the liver does. Unlike free fatty acids, ketone bodies can cross the [[blood-brain barrier]] and are therefore available as fuel for the cells of the [[central nervous system]], 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 [[starvation]], a [[low-carbohydrate diet]], prolonged heavy exercise, and uncontrolled [[Type 1 diabetes|type-1 diabetes mellitus]] is known as [[ketosis]], and in its extreme form in out-of-control type-1 diabetes mellitus, as [[ketoacidosis]].
** On the other hand, when the [[insulin]] concentration in the blood is high, and that of [[glucagon]] 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 [[cytoplasm]].<ref name="stryer2" /> There it is cleaved by [[ATP citrate lyase]] 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| pmid = 17344645 | url = http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ArtikelNr=100426&Ausgabe=232805&ProduktNr=224036 | accessdate = 2010-08-30 | quote = this process is outlined graphically in page 73}}</ref> This cytosolic acetyl-CoA can then be used to synthesize fatty acids through carboxylation by [[acetyl-CoA carboxylase]] into [[Malonyl-CoA|malonyl CoA]], 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=547, 556 |isbn=0-471-21495-7}}</ref> This conversion occurs primarily in the liver, [[adipose tissue]] and lactating [[mammary gland]]s, where the fatty acids are combined with [[glycerol]] to form [[triglyceride]]s, the major fuel reservoir of most animals. Fatty acids are also components of the [[phospholipid]]s that make up the bulk of the [[lipid bilayer]]s of all [[cellular membrane]]s.<ref name="stryer2" />
** In plants, ''de novo'' fatty acid synthesis occurs in the [[plastid]]s. Many [[seed]]s accumulate large reservoirs of seed oils to support [[germination]] and early growth of the seedling before it is a net [[photosynthesis|photosynthetic]] organism.
** The [[cytosol]]ic acetyl-CoA can also condense with [[acetoacetyl-CoA]] to form 3-hydroxy-3-methylglutaryl-CoA ([[HMG-CoA]]) which is the rate-limiting step controlling the [[Mevalonate pathway|synthesis of cholesterol]].<ref name="stryer2" /> [[Cholesterol]] can be used as is, as a structural component of cellular membranes, or it can be used to synthesize [[Steroid#Steroidogenesis|steroid hormones]], [[Bile acids|bile salts]], and [[vitamin D]].<ref name="stryer2" /><ref name="Voet" />
** Acetyl-CoA can be [[carboxylated]] in the cytosol by [[acetyl-CoA carboxylase]], giving rise to [[malonyl-CoA]], a substrate required for synthesis of [[flavonoid]]s and related [[polyketide]]s, for elongation of fatty acids to produce [[wax]]es, [[cuticle]], and seed oils in members of the [[Brassica]] family, and for [[malonate|malonation]] 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|pages=182–203|doi=10.1105/tpc.104.026211|last1=Fatland|first1=B. L.|pmc=544498}}</ref> In plants, these include [[sesquiterpene]]s, [[brassinosteroid]]s (hormones), and membrane [[sterol]]s.
* [[Steroid synthesis]]:
** Acetyl-CoA participates in the [[mevalonate pathway]] by partaking in the synthesis of [[hydroxymethyl glutaryl-CoA]].
* [[Acetylcholine]] synthesis:
** Acetyl-CoA is also an important component in the biogenic synthesis of the [[neurotransmitter]] [[acetylcholine]]. [[Choline]], in combination with acetyl-CoA, is catalyzed by the enzyme [[choline acetyltransferase]] to produce acetylcholine and [[coenzyme A]] as abyproduct.
* [[Melatonin]] synthesis
* Acetylation
** Acetyl-CoA is also the source of the acetyl group incorporated onto certain [[lysine]] residues of [[histone]] and nonhistone proteins in the [[posttranslational modification]] [[acetylation]]. This acetylation is catalyzed by [[acetyltransferases]]. This acetylation affects [[cell growth]], [[mitosis]], and [[apoptosis]].<ref>{{Cite journal|last=Yi|first=C. H.|last2=Vakifahmetoglu-Norberg|first2=H.|last3=Yuan|first3=J.|date=2011-01-01|title=Integration of Apoptosis and Metabolism|url=http://symposium.cshlp.org/content/76/375|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}}</ref>
*Allosteric regulator
** Acetyl-CoA serves as an [[allosteric regulation|allosteric regulator]] of [[pyruvate dehydrogenase kinase]] (PDK). It regulates through the ratio of acetyl-CoA versus CoA. Increased concentration of acetyl-CoA activates PDK.<ref>{{Cite journal|last=Pettit|first=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|url=http://www.sciencedirect.com/science/article/pii/S0006291X75801859|journal=Biochemical and Biophysical Research Communications|volume=65|issue=2|pages=575–582|doi=10.1016/S0006-291X(75)80185-9}}</ref>
** Acetyl-CoA is also an allosteric activator of [[pyruvate carboxylase]].<ref>{{Cite journal|last=Jitrapakdee|first=Sarawut|last2=Maurice|first2=Martin St.|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==
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=J. Biol. Chem. |volume=243 |issue=13 |pages=3603–11 |date=July 1968 |pmid=4872726}}</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=J. Biol. Chem. |volume=285 |issue=3 |pages=1627–33 |date=January 2010 |pmid=19933275 |doi=10.1074/jbc.M109.080556 |url= |pmc=2804320}}</ref>[[File:CoA_Sources_and_Uses.png|thumb|Some of the sources that CoA comes from and uses in the cell.]]
''Click on genes, proteins and metabolites below to visit [[Portal:Gene Wiki|Gene Wiki]] pages and related Wikipedia articles. The pathway can be downloaded and edited at [http://www.wikipathways.org WikiPathways].''
{| 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==
=== Energy production ===
* [[Malonyl-CoA decarboxylase]]


==References==
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 name=":1">{{Cite book|url=http://biochem.science.oregonstate.edu/files/biochem/ahern/Biochemistry%20Free%20For%20All%201.1compressed.pdf|title=Biochemistry Free For All|last=Ahern|first=Kevin|last2=Rajagopal|first2=Indira|last3=Tan|first3=Taralyn|publisher=Creative Commons|year=2017|isbn=|location=|pages=}}</ref><ref>{{Cite journal|last=Alberts|first=Bruce|last2=Johnson|first2=Alexander|last3=Lewis|first3=Julian|last4=Raff|first4=Martin|last5=Roberts|first5=Keith|last6=Walter|first6=Peter|date=2002|title=How Cells Obtain Energy from Food|url=https://www.ncbi.nlm.nih.gov/books/NBK26882/|language=en}}</ref>
{{reflist|30em}}


==External links==
=== Regulation ===
* {{MeshName|Acetyl+Coenzyme+A}}
When there is excess glucose, coenzyme A is used in the cytosol for synthesis of fatty acids.<ref name=":2">{{Cite journal|last=Shi|first=Lei|last2=Tu|first2=Benjamin P.|date=April 2015|title=Acetyl-CoA and the Regulation of Metabolism: Mechanisms and Consequences|journal=Current Opinion in Cell Biology|volume=33|pages=125–131|doi=10.1016/j.ceb.2015.02.003|issn=0955-0674|pmc=4380630|pmid=25703630}}</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 journal|last=Berg|first=Jeremy M.|last2=Tymoczko|first2=John L.|last3=Stryer|first3=Lubert|date=2002|title=Acetyl Coenzyme A Carboxylase Plays a Key Role in Controlling Fatty Acid Metabolism|url=https://www.ncbi.nlm.nih.gov/books/NBK22381/|language=en}}</ref>


{{Nootropics}}
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]].<ref name=":1" />
{{Cholesterol metabolism intermediates}}

{{Glycolysis}}
New research has found that protein CoAlation plays an important role in regulation of the oxidative stress response. Protein CoAlation plays a similar role to [[S-Glutathionylation|glutathionylation]] in the cell, and prevents the irreversible oxidation of the [[Thiol|thiol group]] in cysteine on the surface of cellular proteins, while also directly regulating enzymatic activity in response to oxidative or metabolic stress.<ref>{{Cite journal|last=Tsuchiya|first=Yugo|last2=Peak-Chew|first2=Sew Yeu|last3=Newell|first3=Clare|last4=Miller-Aidoo|first4=Sheritta|last5=Mangal|first5=Sriyash|last6=Zhyvoloup|first6=Alexander|last7=Bakovic´|first7=Jovana|last8=Malanchuk|first8=Oksana|last9=Pereira|first9=Gonçalo C.|date=2017-07-15|title=Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells|journal=Biochemical Journal|volume=474|issue=14|pages=2489–2508|doi=10.1042/BCJ20170129|issn=0264-6021|pmc=5509381|pmid=28341808}}</ref>
{{Amino acid metabolism intermediates}}

{{Acetylcholine receptor modulators}}
==Use in biological research==
Coenzyme A is available from various chemical suppliers as the free acid and or lithium or sodium salts. The free acid of coenzyme A is detectably unstable, with ~5% degradation observed after 6 months when stored at −20˚C,<ref name="Dawson 1989 p. ">{{cite book | last=Dawson | first=R. M. C. | title=Data for biochemical research | publisher=Clarendon Press | location=Oxford | year=1989 | isbn=0-19-855299-8 | pages=118–119}}</ref> and near complete degradation after 1 month at 37˚C.<ref>{{cite web|title=Datasheet for free acid coenzyme A|url=http://www.oycus.com/wp-content/uploads/2014/08/Co-A.pdf|publisher=Oriental Yeast Co., LTD.}}</ref> The lithium and sodium salts of CoA are more stable, with negligible degradation noted over several months at various temperatures.<ref>{{cite web|title=Datasheet for lithium salt coenzyme A|url=http://www.oycus.com/wp-content/uploads/2014/08/Co-A-Li.pdf|publisher=Oriental Yeast Co., LTD.}}</ref> Aqueous solutions of coenzyme A are unstable above pH 8, with 31% of activity lost after 24 hours at 25˚C and pH 8. CoA stock solutions are relatively stable when frozen at pH 2–6. The major route of CoA activity loss is likely the air oxidation of CoA to CoA disulfides. CoA mixed disulfides, such as CoA-S-S-glutathione, are commonly noted contaminants in commercial preparations of CoA.<ref name="Dawson 1989 p. "/> Free CoA can be regenerated from CoA disulfide and mixed CoA disulfides with reducing agents such as [[dithiothreitol|DTT]] or [[2-Mercaptoethanol|BME]].

==Non-exhaustive list of Coenzyme A-activated Acyl Groups==
{{Category see also|Thioesters of coenzyme A}}
*[[Acetyl-CoA]]
*[[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]])
**[[Propionyl-CoA]]
**[[Butyryl-CoA]]
**[[Myristoyl-CoA]]
**[[Crotonyl-CoA]]
*[[Acetoacetyl-CoA]]
*[[Coumaroyl-Coenzyme A|Coumaroyl-CoA]] (used in [[flavonoid]] and [[stilbenoid]] biosynthesis)
*[[Benzoyl-CoA]]
*[[Phenylacetyl-CoA]]
* Acyl derived from [[dicarboxylic acid]]s
**[[Malonyl-CoA]] (important in chain elongation in [[fatty acid biosynthesis]] and [[polyketide]] biosynthesis)
**[[Succinyl-CoA]] (used in [[heme]] biosynthesis)
**[[Hydroxymethylglutaryl-CoA]] (used in [[isoprenoid]] biosynthesis)
**[[pimelate|Pimelyl-CoA]] (used in [[biotin]] biosynthesis)

== References ==
{{reflist}}

==Bibliography==
*{{cite book |title=Lehninger: Principles of Biochemistry |edition=4th |first=David L. |last=Nelson |first2=Michael M. |last2=Cox |location=New York |year=2005 |publisher=W.H. Freeman |isbn=0-7167-4339-6 }}

{{Commons category|Coenzyme A}}

{{Enzyme cofactors}}


{{portal bar|Metabolism}}
{{portal bar|Metabolism}}


{{DEFAULTSORT:Acetyl-Coa}}
[[Category:Coenzymes]]
[[Category:Cholinergics]]
[[Category:Metabolism]]
[[Category:Metabolism]]
[[Category:Thiols]]
[[Category:Thioesters of coenzyme A]]









'''아세틸 조효소 A'''({{llang|en|acetyl coenzyme A}}) 혹은 '''아세틸-CoA'''({{llang|en|acetyl-CoA}})는 [[물질대사|대사]]에서 중요한 분자로 많은 생화학 반응에 이용된다. 아세틸-CoA의 주요 기능은 아세틸기의 탄소 원자를 [[시트르산 회로]](크렙스 회로)로 옮겨 산화를 거쳐 에너지를 생산하는 것이다. 아세틸-CoA는 [[아세트산]]이 운반하는 [[아실기]]와 [[조효소 A]]의 [[티올기]] 사이에 [[황화에스터]] 결합한 분자이다. 아세틸-CoA는 미토콘드리아 기질에서 일어나는, [[세포호흡#.EC.9C.A0.EA.B8.B0.ED.98.B8.ED.9D.A1|유기 세포 호흡]]의 두번째 단계인 피루브산 탈탄산화 과정에서 생산되어 시트르산 회로에 들어간다.
아세틸-CoA는 [[아세트산]]이 운반하는 [[아실기]]와 [[조효소 A]]의 [[티올기]] 사이에 [[황화에스터]] 결합한 분자이다. 아세틸-CoA는 미토콘드리아 기질에서 일어나는, [[세포호흡#.EC.9C.A0.EA.B8.B0.ED.98.B8.ED.9D.A1|유기 세포 호흡]]의 두번째 단계인 피루브산 탈탄산화 과정에서 생산되어 시트르산 회로에 들어간다.


아세틸-CoA는 [[신경전달물질]]인 [[아세틸콜린]]의 생합성에도 중요한 요소이다. [[콜린 (복합체)|콜린]]과 아세틸-CoA가 [[콜린 아세틸전이효소]]의 촉매 작용에 의하여 반응하여 아세틸콜린과 부산물로 조효소 A를 생산한다.
아세틸-CoA는 [[신경전달물질]]인 [[아세틸콜린]]의 생합성에도 중요한 요소이다. [[콜린 (복합체)|콜린]]과 아세틸-CoA가 [[콜린 아세틸전이효소]]의 촉매 작용에 의하여 반응하여 아세틸콜린과 부산물로 조효소 A를 생산한다.

2018년 7월 25일 (수) 19:41 판

아세틸-CoA
일반적인 성질
IUPAC 이름 S-[2-[3-[[(2R)-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethyl] ethanethioate
화학식 C23H38N7O17P3S
CAS 번호 72-89-9
물리적 성질
분자량 809.57 g/mol
열화학적 성질
안전성

아세틸 조효소 A(영어: acetyl coenzyme A) 또는 아세틸-CoA(영어: acetyl-CoA)는 단백질, 탄수화물 및 지질 대사 등 많은 생화학 반응에 참여하는 분자이다. 아세틸-CoA의 주요 기능은 아세틸기를 시트르산 회로에 전달하여 에너지 생산을 위해 산화되도록 하는 것이다. 조효소 A(CoA-SH 또는 CoA)에서 판토텐산의 하이드록시기는 3′-포스포아데노신 이인산과 인산에스터(인산에스테르) 결합을 하고 있으며, 판토텐산의 카복실기는 β-메르캅토에틸아민과 아마이드 결합을 하고 있다. 아세틸-CoA의 아세틸기(오른쪽 구조식에서 파란색으로 표시)는 β-메르캅토에틸아민 부분의 -SH기와 티오에스터(티오에스테르) 결합을 형성한다. 이러한 티오에스터(티오에스테르) 결합은 특히 반응성이 강한 "고에너지" 결합이다. 티오에스터(티오에스테르) 결합의 가수분해는 발열 반응()이다.Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism.[1] Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production. Coenzyme A (CoASH or CoA) consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid through an amide linkage [2] and 3'-phosphorylated ADP. The acetyl group (indicated in blue in the structural diagram on the right) of acetyl-CoA is linked to the sulfhydryl substituent of the β-mercaptoethylamine group. This thioester linkage is a "high energy" bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol).

CoA is acetylated to acetyl-CoA by the breakdown of carbohydrates through glycolysis and by the breakdown of fatty acids through β-oxidation. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and water, and the energy released captured in the form of 11 ATP and one GTP per acetyl group.

Konrad Bloch and Feodor Lynen were awarded the 1964 Nobel Prize in Physiology and Medicine for their discoveries linking acetyl-CoA and fatty acid metabolism. Fritz Lipmann won the Nobel Prize in 1953 for his discovery of the cofactor coenzyme A.

Direct synthesis

The acetylation of CoA is determined by the carbon sources.[3][4]

Extramitochondrial

Intramitochondrial

Pyruvate dehydrogenase complex reaction
  • At high glucose levels, acetyl-CoA is produced through glycolysis.[10] Pyruvate undergoes oxidative decarboxylation in which it loses its carboxyl group (as carbon dioxide) 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 pyruvate dehydrogenase complex. Other conversions between pyruvate and acetyl-CoA are possible. For example, pyruvate formate lyase disproportionates pyruvate into acetyl-CoA and formic acid.
β-Oxidation of fatty acids

Functions

Intermediates in various pathways

Interactive pathway map

Click on genes, proteins and metabolites below to visit Gene Wiki pages and related Wikipedia articles. The pathway can be downloaded and edited at WikiPathways.

틀:TCACycle WP78 틀:StatinPathway WP430

See also

References

  1. ↑ “Acetyl CoA Crossroads”. 《chemistry.elmhurst.edu》. 2016년 11월 8일에 확인함. 
  2. ↑ “Fatty Acids -- Structure of Acetyl CoA”. 《library.med.utah.edu》. 2017년 6월 2일에 확인함. 
  3. ↑ Hynes, Michael J.; Murray, Sandra L. (2010년 7월 1일). “ATP-Citrate Lyase Is Required for Production of Cytosolic Acetyl Coenzyme A and Development in Aspergillus nidulans”. 《Eukaryotic Cell》 (영어) 9 (7): 1039–1048. doi:10.1128/EC.00080-10. ISSN 1535-9778. PMC 2901662. PMID 20495057. 
  4. ↑ Wellen, Kathryn E.; Thompson, Craig B. (2012년 4월 1일). “A two-way street: reciprocal regulation of metabolism and signalling”. 《Nature Reviews Molecular Cell Biology》 (영어) 13 (4): 270–276. doi:10.1038/nrm3305. ISSN 1471-0072. PMID 22395772. 
  5. ↑ Storey, Kenneth B. (2005년 2월 25일). 《Functional Metabolism: Regulation and Adaptation》 (영어). John Wiley & Sons. ISBN 9780471675570. 
  6. ↑ “ACLY ATP citrate lyase [Homo sapiens (human)] - Gene - NCBI”. 《www.ncbi.nlm.nih.gov》. 2016년 11월 6일에 확인함. 
  7. ↑ Ragsdale, S. W. (2004). “Life with carbon monoxide”. 《CRC Critical Reviews in Biochemistry and Molecular Biology》 39: 165–195. 
  8. ↑ Chatterjea (2004년 1월 1일). 《Textbook of Biochemistry for Dental/Nursing/Pharmacy Students》 (영어). Jaypee Brothers Publishers. ISBN 9788180612046. 
  9. ↑ 가 나 Berg, Jeremy M.; Tymoczko, John L.; Stryer, Lubert (2002). 《Biochemistry》 5판. W. H. Freeman. ISBN 0716730510. 
  10. ↑ Blackstock, James C. (2014년 6월 28일). 《Guide to Biochemistry》 (영어). Butterworth-Heinemann. ISBN 9781483183671. 
  11. ↑ Houten, Sander Michel; Wanders, Ronald J. A. (2010년 3월 2일). “A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation”. 《Journal of Inherited Metabolic Disease》 (영어) 33 (5): 469–477. doi:10.1007/s10545-010-9061-2. ISSN 0141-8955. PMC 2950079. PMID 20195903. 
  12. ↑ 가 나 다 라 마 바 사 Stryer, Lubert (1995). 《Biochemistry.》 Four판. New York: W.H. Freeman and Company. 510–515, 559–565, 581–613, 614–623, 775–778쪽. ISBN 0-7167-2009-4. 
  13. ↑ “Oxidation of fatty acids”. 
  14. ↑ “Ketone body metabolism”. University of Waterloo. 
  15. ↑ 가 나 Ferre, P.; F. Foufelle (2007). “SREBP-1c Transcription Factor and Lipid Homeostasis: Clinical Perspective”. 《Hormone Research》 68 (2): 72–82. doi:10.1159/000100426. PMID 17344645. 2010년 8월 30일에 확인함. this process is outlined graphically in page 73 
  16. ↑ 가 나 Voet, Donald; Judith G. Voet; Charlotte W. Pratt (2006). 《Fundamentals of Biochemistry, 2nd Edition》. John Wiley and Sons, Inc. 547, 556쪽. ISBN 0-471-21495-7. 
  17. ↑ Fatland, B. L. (2005). “Reverse Genetic Characterization of Cytosolic Acetyl-CoA Generation by ATP-Citrate Lyase in Arabidopsis”. 《The Plant Cell Online》 17: 182–203. doi:10.1105/tpc.104.026211. PMC 544498. 
  18. ↑ Yi, C. H.; Vakifahmetoglu-Norberg, H.; Yuan, J. (2011년 1월 1일). “Integration of Apoptosis and Metabolism”. 《Cold Spring Harbor Symposia on Quantitative Biology》 (영어) 76: 375–387. doi:10.1101/sqb.2011.76.010777. ISSN 0091-7451. PMID 22089928. 
  19. ↑ Pettit, Flora H.; Pelley, John W.; Reed, Lester J. (1975년 7월 22일). “Regulation of pyruvate dehydrogenase kinase and phosphatase by acetyl-CoA/CoA and NADH/NAD ratios”. 《Biochemical and Biophysical Research Communications》 65 (2): 575–582. doi:10.1016/S0006-291X(75)80185-9. 
  20. ↑ Jitrapakdee, Sarawut; Maurice, Martin St.; Rayment, Ivan; Cleland, W. Wallace; Wallace, John C.; Attwood, Paul V. (2008년 8월 1일). “Structure, Mechanism and Regulation of Pyruvate Carboxylase”. 《The Biochemical Journal》 413 (3): 369–387. doi:10.1042/BJ20080709. ISSN 0264-6021. PMC 2859305. PMID 18613815. 

External links

틀:Nootropics 틀:Cholesterol metabolism intermediates 틀:Glycolysis 틀:Amino acid metabolism intermediates 틀:Acetylcholine receptor modulators



아세틸-CoA는 아세트산이 운반하는 아실기와 조효소 A의 티올기 사이에 황화에스터 결합한 분자이다. 아세틸-CoA는 미토콘드리아 기질에서 일어나는, 유기 세포 호흡의 두번째 단계인 피루브산 탈탄산화 과정에서 생산되어 시트르산 회로에 들어간다.

아세틸-CoA는 신경전달물질인 아세틸콜린의 생합성에도 중요한 요소이다. 콜린과 아세틸-CoA가 콜린 아세틸전이효소의 촉매 작용에 의하여 반응하여 아세틸콜린과 부산물로 조효소 A를 생산한다.

1953년 프리츠 리프먼(Fritz Lipmann)은 보조인자 조효소 A를 발견한 공로로, 1964년 콘라트 블로흐(Konrad Bloch)와 페오도어 리넨(독일어: Feodor Lynen)이 아세틸-CoA와 지방산 대사의 연결점을 찾은 공로로 노벨 생리학·의학상을 수상한다.

생합성

아세틸-CoA와 피루브산 사이에 전환되는 반응이 있고, 직접적으로 아세틸-CoA를 합성하는 반응이 있다.

  • 피루브산 탈수소효소 복합체가 피루브산을 아세틸-CoA로 산화시킨다. 이 반응은 비가역적 반응으로 전체적으로 산화 탈카복실화 반응이다. 피루브산의 카복실기가 CO2 분자로 제거되고 남은 아세틸기는 조효소 A와 결합하여 아세틸-CoA가 된다. NADH는 전자 2개를 가진 수소 음이온(hydride ion, H-)을 전자전달계로 이동시키고, 최종적으로 전자는 산소 혹은 황(혐기성 미생물의 경우)과 같은 전자 수용체로 전해진다.[1]
  • 아세틸-CoA와 피루브산 사이의 전환은 다른 효소로도 이루어진다. 예를 들어, 피루브산 포름산 분해효소(pyruvate formate lyase)는 피루브산을 아세틸-CoA와 포름산으로 분해한다.
  • 조효소 A와 아세트산을 통해 공급되는 아세틸기는 아세틸-CoA 합성효소(acetyl-CoA synthetase)에 의하여 직접적으로 연결된다. 이 과정은 당 대사와 연관이 있지만, 시트르산 회로의 시작점으로는 피루브산 탈수소효소 경로가 아세틸-CoA 합성효소 경로보다 일반적이다.

지방산 대사

동물에게서 아세틸-CoA와 다른 아실-CoA 조효소는 탄수화물 대사와 지방 대사의 균형에 필수적인 요소이다. 정상 상태에서 지방산 대사로 인하여 생성된 아세틸-CoA는 시트르산 회로에 공급되어 세포의 에너지가 된다. 혈중 지방산 농도가 높을 때, 간에서는 세포가 요구하는 에너지를 초과하는 양의 아세틸-CoA가 생산된다. 초과 분량의 아세틸-CoA는 케톤체로 전환되어 혈류를 따라 순환하는데, 케톤체의 혈중 농도가 과도하게 높은 상태를 케톤증(ketosis)라고 한다.

식물의 경우 "새로운(de novo)" 지방산 합성은 색소체에서 일어난다. 실제 광합성을 하는 식물이 되기 전에 발아(germination)와 초기 성장을 위해서 식물의 종자는 많은 양의 기름을 저장한다. 지방산은 막지질에 포함되어 있다.

기타 반응

  • 메발론산 경로(mevalonate pathway) : 두 아세틸-CoA 분자가 축합반응(condensation reaction)을 거쳐 이소프레노이드(isoprenoid)로 합성되는 경로이다. 이 경로의 속도제한단계 효소는 HMG-CoA 환원효소(HMG-CoA reductase)이다. 동물의 경우 HMG-CoA는 콜레스테롤과 케톤체 합성의 주요 전구체이다.
  • 번역 후 변형(posttranslational modification) : 히스톤 및 비히스톤 단백질의 특정 라이신 잔기를 아세틸화할 때 아세틸-CoA가 아세틸기를 공급한다. 이 반응은 아세틸전이효소(acetyltransferase)가 촉매 작용한다.
  • 식물과 동물에서, 세포질의 아세틸-CoA는 ATP 시트르산 분해효소(ATP citrate lyase)에 의해 합성된다.[2] (동물의 경우) 혈당량이 높으면 포도당은 세포질에서 피루브산으로 분해되고(해당), 미토콘드리아에서 아세틸-CoA로 전환된다. 아세틸-CoA가 과다하면 시트르산이 증가하고, 여분의 시트르산은 세포질로 수송되어 세포질 아세틸-CoA의 양을 증가시킨다.
  • 아세틸-CoA는 세포질에서 아세틸-CoA 카복시화효소에 의하여 카복실화되어 말로닐-CoA(malonyl-CoA)가 된다. 말로닐-CoA는 플라보노이드(flavonoid) 및 그와 연관된 폴리케티드(polyketide)를 합성하고, 단백질과 기타 식물화학성분(파이토케미컬, phytochemical)을 말로닐화 하는데 쓰인다. 왁스, 큐티클(cuticle), 배추속(Brassica) 식물의 종자유 또한 말로닐-CoA를 통한 지방산 신장(elongation)으로 합성된다.[3] 세스퀴테르펜(sesquiterpene), 브라시노스테로이드(brassinosteroid)와 같은 식물 호르몬과 막 스테롤이 역시 이 방법으로 합성된다.

출처

  1. ↑ Nelson D.L., Cox M.M. (2005). “16 The Citric Acid Cycle”. Lehninger Principles of Biochemistry (영어) 4판. W.H. Freeman and Company. ISBN 0-7167-4339-6. 
  2. ↑ Fatland, B. L.; Ke J., Anderson MD., Mentzen WI., Cui LW., Allred CC., Johnston JL., Nikolau BJ., Wurtele ES. (2002). “Molecular Characterization of a Heteromeric ATP-Citrate Lyase That Generates Cytosolic Acetyl-Coenzyme a in Arabidopsis”. Plant Physiology (영어) 130 (2): 740. doi:10.1104/pp.008110. PMC 166603. PMID 12376641. 
  3. ↑ Fatland, B. L. (2005). “Reverse Genetic Characterization of Cytosolic Acetyl-CoA Generation by ATP-Citrate Lyase in Arabidopsis”. The Plant Cell Online (영어) 17: 182. doi:10.1105/tpc.104.026211. 
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