ACOT2: Difference between revisions

'''Acyl-CoA thioesterase 2''', also known as '''ACOT2''', is an [[enzyme]] which in humans is encoded by the ''ACOT2'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: ACOT2 acyl-CoA thioesterase 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10965| accessdateaccess-date = }}</ref><ref name="pmid10944470">{{cite journal | vauthors = Jones JM, Gould SJ | title = Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase | journal = Biochemical and Biophysical Research Communications | volume = 275 | issue = 1 | pages = 233–40233–240 | date = AugAugust 2000 | pmid = 10944470 | doi = 10.1006/bbrc.2000.3285 }}</ref><ref name="pmid16940157">{{cite journal | vauthors = Hunt MC, Rautanen A, Westin MA, Svensson LT, Alexson SE | title = Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs | journal = FASEB Journal | volume = 20 | issue = 11 | pages = 1855–641855–1864 | date = SepSeptember 2006 | pmid = 16940157 | doi = 10.1096/fj.06-6042com | s2cid = 501610 | urldoi-access = https://arrow.dit.ie/cgi/viewcontent.cgi?article=1028&context=scschbioartfree }}</ref>

Acyl-CoA thioesterases, such as ACOT2, are a group of enzymes that hydrolyze [[Coenzyme A]] (CoA) [[ester]]s, such as acyl-CoAs, bile CoAs, and CoA esters of prostaglandins, to the corresponding free acid and CoA.<ref name="pmid16103133">{{cite journal | vauthors = Hunt MC, Yamada J, Maltais LJ, Wright MW, Podesta EJ, Alexson SE | title = A revised nomenclature for mammalian acyl-CoA thioesterases/hydrolases | journal = Journal of Lipid Research | volume = 46 | issue = 9 | pages = 2029–322029–2032 | date = SepSeptember 2005 | pmid = 16103133 | doi = 10.1194/jlr.E500003-JLR200 | doi-access = free }}</ref> ACOT2 shows high acyl-CoA [[thioesterase]] activity on medium- and long-chain acyl-CoAs, with an optimal pH of 8.5. It is most active on [[myristic acid|myristoyl]]-CoA but also shows high activity on [[palmitic acid|palmitoyl]]-CoA, [[stearic acid|stearoyl]]-CoA, and [[arachidic acid|arachidoyl]]-CoA.<ref name="pmid10944470"/>

== Function ==

These enzymes use the same [[substrate (chemistry)|substrate]]s as long-chain acyl-CoA synthetases, but have a unique purpose in that they generate the free acid and CoA, as opposed to long-chain acyl-CoA synthetases, which ligate fatty acids to CoA, to produce the CoA ester.<ref>{{cite journal |last1 vauthors = Mashek|first1= DG|last2=, Bornfeldt|first2= KE|last3=, Coleman|first3= RA|last4=, Berger|first4= J|last5=, Bernlohr|first5= DA|last6=, Black|first6= P|last7=, DiRusso|first7= CC|last8=, Farber|first8= SA|last9=, Guo|first9= W|last10=, Hashimoto|first10= N|last11=, Khodiyar|first11= V|last12=, Kuypers|first12= FA|last13=, Maltais|first13= LJ|last14=, Nebert|first14= DW|last15=, Renieri|first15= A|last16=, Schaffer|first16= JE|last17=, Stahl|first17= A|last18=, Watkins|first18= PA|last19=, Vasiliou|first19= V|last20=, Yamamoto|first20= TT | title = Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family. | journal = Journal of Lipid Research|date=October 2004| volume = 45 | issue = 10 | pages =1958–61 1958–1961 | date = October 2004 | pmid = 15292367 | doi = 10.1194/jlr.e400002-jlr200 | doi-access = free }}</ref> The role of the ACOT- family of enzymes is not well understood; however, it has been suggested that they play a crucial role in regulating the intracellular levels of CoA esters, Coenzyme A, and free fatty acids. Recent studies have shown that Acyl-CoA esters have many more functions than simply an energy source. These functions include [[allosteric regulation]] of enzymes such as [[acetyl-CoA carboxylase]],<ref>{{cite journal |last1 vauthors = Ogiwara|first1= H|last2=, Tanabe|first2= T|last3=, Nikawa|first3= J|last4=, Numa|first4= S | title = Inhibition of rat-liver acetyl-coenzyme-A carboxylase by palmitoyl-coenzyme A. Formation of equimolar enzyme-inhibitor complex. | journal = European Journal of Biochemistry|date=15 August 1978| volume = 89 | issue = 1 | pages = 33–41 | date = August 1978 | pmid = 29756 | doi = 10.1111/j.1432-1033.1978.tb20893.x }}</ref> [[hexokinase]] IV,<ref>{{cite journal |last1 vauthors = Srere|first1= PA | title = Palmityl-coenzyme A inhibition of the citrate-condensing enzyme. | journal = Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism |date=2 Decembervolume 1965|volume= 106 | issue = 3 | pages =445–55 445–455 | date = December 1965 | pmid = 5881327 | doi = 10.1016/0005-2760(65)90061-5 }}</ref> and the citrate condensing enzyme. Long-chain acyl-CoAs also regulate opening of [[ATP-sensitive potassium channel]]s and activation of [[Calcium ATPase]]s, thereby regulating [[insulin]] secretion.<ref>{{cite journal |last1 vauthors = Gribble|first1= FM|last2=, Proks|first2= P|last3=, Corkey|first3= BE|last4=, Ashcroft|first4= FM | title = Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA. | journal = The Journal of Biological Chemistry|date=9 October 1998| volume = 273 | issue = 41 | pages =26383–7 26383–26387 | date = October 1998 | pmid = 9756869 | doi = 10.1074/jbc.273.41.26383 | doi-access = free }}</ref> A number of other cellular events are also mediated via acyl-CoAs, for example signal transduction through [[protein kinase C]], inhibition of [[retinoic acid]]-induced apoptosis, and involvement in budding and fusion of the [[endomembrane system]].<ref>{{cite journal |last1 vauthors = Nishizuka|first1= Y | title = Protein kinase C and lipid signaling for sustained cellular responses. | journal = FASEB Journal|date=April 1995| volume = 9 | issue = 7 | pages =484–96 484–496 | date = April 1995 | pmid = 7737456 | doi = 10.1096/fasebj.9.7.7737456 | s2cid = 31065063 | doi-access = free }}</ref><ref>{{cite journal |last1 vauthors = Glick|first1= BS|last2=, Rothman|first2= JE | title = Possible role for fatty acyl-coenzyme A in intracellular protein transport. | journal = Nature | volume = 326 | issue = 6110 | pages =309–12 309–312 | year = 1987 | pmid = 3821906 | doi = 10.1038/326309a0 |year s2cid =1987 4306469 | bibcode = 1987Natur.326..309G|s2cid=4306469 }}</ref><ref>{{cite journal |last1 vauthors = Wan|first1= YJ|last2=, Cai|first2= Y|last3=, Cowan|first3= C|last4=, Magee|first4= TR | title = Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells. | journal = Cancer Letters|date=1 June 2000| volume = 154 | issue = 1 | pages = 19–27 | date = June 2000 | pmid = 10799735 | doi = 10.1016/s0304-3835(00)00341-4 }}</ref> Acyl-CoAs also mediate protein targeting to various membranes and regulation of [[G Protein]] α subunits, because they are substrates for protein acylation.<ref>{{cite journal |last1 vauthors = Duncan|first1= JA|last2=, Gilman|first2= AG | title = A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS). | journal = The Journal of Biological Chemistry|date=19 June 1998| volume = 273 | issue = 25 | pages =15830–7 15830–15837 | date = June 1998 | pmid = 9624183 | doi = 10.1074/jbc.273.25.15830 | doi-access = free }}</ref> In the [[mitochondria]], acyl-CoA esters are involved in the acylation of mitochondrial NAD+ dependent [[dehydrogenase]]s; because these enzymes are responsible for [[Amino acid#Catabolism|amino acid catabolism]], this acylation renders the whole process inactive. This mechanism may provide metabolic crosstalk and act to regulate the [[NADH]]/NAD+ ratio in order to maintain optimal mitochondrial [[beta oxidation]] of fatty acids.<ref>{{cite journal |last1 vauthors = Berthiaume|first1= L|last2=, Deichaite|first2= I|last3=, Peseckis|first3= S|last4=, Resh|first4= MD | title = Regulation of enzymatic activity by active site fatty acylation. A new role for long chain fatty acid acylation of proteins. | journal = The Journal of Biological Chemistry|date=4 March 1994| volume = 269 | issue = 9 | pages =6498–505 6498–6505 | date = March 1994 | pmid = 8120000 | doi = 10.1016/S0021-9258(17)37399-4 |pmid=8120000| doi-access = free }}</ref> The role of CoA esters in [[lipid metabolism]] and numerous other intracellular processes are well defined, and thus it is hypothesized that ACOT- enzymes play a role in modulating the processes these metabolites are involved in.<ref>{{cite journal |last1 vauthors = Hunt|first1= MC|last2=, Alexson|first2= SE | title = The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism. | journal = Progress in Lipid Research|date=March 2002| volume = 41 | issue = 2 | pages = 99–130 | date = March 2002 | pmid = 11755680 | doi = 10.1016/s0163-7827(01)00017-0 }}</ref>

* {{cite journal | vauthors = Hunt MC, Rautanen A, Westin MA, SvenssonAlexson LTSE, AlexsonHunt SEMC | title = AnalysisMolecular cloning and characterization of thetwo mouse andperoxisome human acylproliferator-CoAactivated thioesterasereceptor alpha (ACOTPPARalpha)-regulated geneperoxisomal clustersacyl-CoA showsthioesterases that| convergent,journal functional= evolutionThe results in a reduced numberJournal of humanBiological peroxisomal ACOTs | journal = FASEB JournalChemistry | volume = 20279 | issue = 1121 | pages = 1855–6421841–21848 | date = SepMay 20062004 | pmid = 1694015715007068 | doi = 10.10961074/fjjbc.06-6042comM313863200 | s2ciddoi-access = 501610 | url = https://arrow.dit.ie/cgi/viewcontent.cgi?article=1028&context=scschbioartfree }}

* {{cite journal | vauthors = HuntGevaert MCK, YamadaGoethals JM, MaltaisMartens LJL, WrightVan MWDamme J, PodestaStaes EJA, AlexsonThomas SEGR, Vandekerckhove J | title = AExploring revisedproteomes nomenclatureand foranalyzing mammalianprotein acylprocessing by mass spectrometric identification of sorted N-CoAterminal thioesterases/hydrolasespeptides | journal = JournalNature of Lipid ResearchBiotechnology | volume = 4621 | issue = 95 | pages = 2029–32566–569 | date = SepMay 20052003 | pmid = 1610313312665801 | doi = 10.11941038/jlr.E500003-JLR200nbt810 | doi-accesss2cid = free23783563 }}

* {{cite journal | vauthors = WestinSuzuki MAY, AlexsonYoshitomo-Nakagawa K, Maruyama K, Suyama SEA, HuntSugano MCS | title = Molecular cloningConstruction and characterization of twoa mousefull peroxisome proliferatorlength-activatedenriched receptorand alphaa (PPARalpha)5'-end-regulatedenriched peroxisomalcDNA acyl-CoA thioesteraseslibrary | journal = The Journal of Biological ChemistryGene | volume = 279200 | issue = 211–2 | pages = 21841–8149–156 | date = MayOctober 20041997 | pmid = 150070689373149 | doi = 10.10741016/jbc.M313863200 | doiS0378-access = free1119(97)00411-3 }}

* {{cite journal | vauthors = GevaertMaruyama K, GoethalsSugano M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove JS | title = ExploringOligo-capping: proteomesa andsimple analyzingmethod proteinto processingreplace bythe masscap spectrometric identificationstructure of sortedeukaryotic N-terminalmRNAs with peptidesoligoribonucleotides | journal = Nature BiotechnologyGene | volume = 21138 | issue = 51–2 | pages = 566–9171–174 | date = MayJanuary 20031994 | pmid = 126658018125298 | doi = 10.10381016/nbt810 | s2cid = 237835630378-1119(94)90802-8 }}