ACOT2

The protein encoded by the ACOT2 gene is part of a family of Acyl-CoA thioesterases, which catalyze the hydrolysis of various Coenzyme A esters of various molecules to the free acid plus CoA. These enzymes have also been referred to in the literature as acyl-CoA hydrolases, acyl-CoA thioester hydrolases, and palmitoyl-CoA hydrolases. The reaction carried out by these enzymes is as follows:

CoA ester + H₂O → free acid + coenzyme A

These enzymes use the same substrates 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.{{cite journal | vauthors = Mashek DG, Bornfeldt KE, Coleman RA, Berger J, Bernlohr DA, Black P, DiRusso CC, Farber SA, Guo W, Hashimoto N, Khodiyar V, Kuypers FA, Maltais LJ, Nebert DW, Renieri A, Schaffer JE, Stahl A, Watkins PA, Vasiliou V, Yamamoto TT | title = Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family | journal = Journal of Lipid Research | volume = 45 | issue = 10 | pages = 1958–1961 | date = October 2004 | pmid = 15292367 | doi = 10.1194/jlr.e400002-jlr200 | doi-access = free }} 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,{{cite journal | vauthors = Ogiwara H, Tanabe T, Nikawa J, Numa 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 | volume = 89 | issue = 1 | pages = 33–41 | date = August 1978 | pmid = 29756 | doi = 10.1111/j.1432-1033.1978.tb20893.x }} hexokinase IV,{{cite journal | vauthors = Srere PA | title = Palmityl-coenzyme A inhibition of the citrate-condensing enzyme | journal = Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | volume = 106 | issue = 3 | pages = 445–455 | date = December 1965 | pmid = 5881327 | doi = 10.1016/0005-2760(65)90061-5 }} and the citrate condensing enzyme. Long-chain acyl-CoAs also regulate opening of ATP-sensitive potassium channels and activation of Calcium ATPases, thereby regulating insulin secretion.{{cite journal | vauthors = Gribble FM, Proks P, Corkey BE, Ashcroft FM | title = Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA | journal = The Journal of Biological Chemistry | volume = 273 | issue = 41 | pages = 26383–26387 | date = October 1998 | pmid = 9756869 | doi = 10.1074/jbc.273.41.26383 | doi-access = free }} 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.{{cite journal | vauthors = Nishizuka Y | title = Protein kinase C and lipid signaling for sustained cellular responses | journal = FASEB Journal | volume = 9 | issue = 7 | pages = 484–496 | date = April 1995 | pmid = 7737456 | doi = 10.1096/fasebj.9.7.7737456 | s2cid = 31065063 | doi-access = free }}{{cite journal | vauthors = Glick BS, Rothman JE | title = Possible role for fatty acyl-coenzyme A in intracellular protein transport | journal = Nature | volume = 326 | issue = 6110 | pages = 309–312 | year = 1987 | pmid = 3821906 | doi = 10.1038/326309a0 | s2cid = 4306469 | bibcode = 1987Natur.326..309G }}{{cite journal | vauthors = Wan YJ, Cai Y, Cowan C, Magee TR | title = Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells | journal = Cancer Letters | volume = 154 | issue = 1 | pages = 19–27 | date = June 2000 | pmid = 10799735 | doi = 10.1016/s0304-3835(00)00341-4 }} Acyl-CoAs also mediate protein targeting to various membranes and regulation of G Protein α subunits, because they are substrates for protein acylation.{{cite journal | vauthors = Duncan JA, Gilman AG | title = A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS) | journal = The Journal of Biological Chemistry | volume = 273 | issue = 25 | pages = 15830–15837 | date = June 1998 | pmid = 9624183 | doi = 10.1074/jbc.273.25.15830 | doi-access = free }} In the mitochondria, acyl-CoA esters are involved in the acylation of mitochondrial NAD+ dependent dehydrogenases; because these enzymes are responsible for 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.{{cite journal | vauthors = Berthiaume L, Deichaite I, Peseckis S, Resh 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 | volume = 269 | issue = 9 | pages = 6498–6505 | date = March 1994 | pmid = 8120000 | doi = 10.1016/S0021-9258(17)37399-4 | doi-access = free }} 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.{{cite journal | vauthors = Hunt MC, Alexson SE | title = The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism | journal = Progress in Lipid Research | volume = 41 | issue = 2 | pages = 99–130 | date = March 2002 | pmid = 11755680 | doi = 10.1016/s0163-7827(01)00017-0 }}

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{{refbegin | 2}}

• {{cite journal | vauthors = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Molecular Systems Biology | volume = 3 | issue = 1 | pages = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }}
• {{cite journal | vauthors = Westin MA, Alexson SE, Hunt MC | title = Molecular cloning and characterization of two mouse peroxisome proliferator-activated receptor alpha (PPARalpha)-regulated peroxisomal acyl-CoA thioesterases | journal = The Journal of Biological Chemistry | volume = 279 | issue = 21 | pages = 21841–21848 | date = May 2004 | pmid = 15007068 | doi = 10.1074/jbc.M313863200 | doi-access = free }}
• {{cite journal | vauthors = Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J | title = Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides | journal = Nature Biotechnology | volume = 21 | issue = 5 | pages = 566–569 | date = May 2003 | pmid = 12665801 | doi = 10.1038/nbt810 | s2cid = 23783563 }}
• {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–156 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
• {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–174 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
• {{cite journal | vauthors = Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HA, Haines JL, Perkicak-Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St George-Hyslop PH | title = Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease | journal = Nature | volume = 375 | issue = 6534 | pages = 754–760 | date = June 1995 | pmid = 7596406 | doi = 10.1038/375754a0 | s2cid = 4308372 | bibcode = 1995Natur.375..754S }}

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• {{UCSC gene info|ACOT2}}
• {{PDBe-KB2|P49753|Acyl-coenzyme A thioesterase 2, mitochondrial}}

{{Thioesterases}}

Category:Human proteins