ACOT2
An Error has occurred retrieving Wikidata item for infobox Acyl-CoA thioesterase 2, also known as ACOT2, is an enzyme which in humans is encoded by the ACOT2 gene.[1][2][3] Acyl-CoA thioesterases, such as ACOT2, are a group of enzymes that hydrolyze Coenzyme A (CoA) esters, such as acyl-CoAs, bile CoAs, and CoA esters of prostaglandins, to the corresponding free acid and CoA.[4] 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 myristoyl-CoA but also shows high activity on palmitoyl-CoA, stearoyl-CoA, and arachidoyl-CoA.[2]
Function
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.[5] 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,[6] hexokinase IV,[7] 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.[8] 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.[9][10][11] Acyl-CoAs also mediate protein targeting to various membranes and regulation of G Protein α subunits, because they are substrates for protein acylation.[12] 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.[13] 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.[14]
References
- ↑ "Entrez Gene: ACOT2 acyl-CoA thioesterase 2".
- ↑ 2.0 2.1 Jones JM, Gould SJ (August 2000). "Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase". Biochemical and Biophysical Research Communications. 275 (1): 233–240. doi:10.1006/bbrc.2000.3285. PMID 10944470.
- ↑ Hunt MC, Rautanen A, Westin MA, Svensson LT, Alexson SE (September 2006). "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". FASEB Journal. 20 (11): 1855–1864. doi:10.1096/fj.06-6042com. PMID 16940157. S2CID 501610.
- ↑ Hunt MC, Yamada J, Maltais LJ, Wright MW, Podesta EJ, Alexson SE (September 2005). "A revised nomenclature for mammalian acyl-CoA thioesterases/hydrolases". Journal of Lipid Research. 46 (9): 2029–2032. doi:10.1194/jlr.E500003-JLR200. PMID 16103133.
- ↑ Mashek DG, Bornfeldt KE, Coleman RA, Berger J, Bernlohr DA, Black P, et al. (October 2004). "Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family". Journal of Lipid Research. 45 (10): 1958–1961. doi:10.1194/jlr.e400002-jlr200. PMID 15292367.
- ↑ Ogiwara H, Tanabe T, Nikawa J, Numa S (August 1978). "Inhibition of rat-liver acetyl-coenzyme-A carboxylase by palmitoyl-coenzyme A. Formation of equimolar enzyme-inhibitor complex". European Journal of Biochemistry. 89 (1): 33–41. doi:10.1111/j.1432-1033.1978.tb20893.x. PMID 29756.
- ↑ Srere PA (December 1965). "Palmityl-coenzyme A inhibition of the citrate-condensing enzyme". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 106 (3): 445–455. doi:10.1016/0005-2760(65)90061-5. PMID 5881327.
- ↑ Gribble FM, Proks P, Corkey BE, Ashcroft FM (October 1998). "Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA". The Journal of Biological Chemistry. 273 (41): 26383–26387. doi:10.1074/jbc.273.41.26383. PMID 9756869.
- ↑ Nishizuka Y (April 1995). "Protein kinase C and lipid signaling for sustained cellular responses". FASEB Journal. 9 (7): 484–496. doi:10.1096/fasebj.9.7.7737456. PMID 7737456. S2CID 31065063.
- ↑ Glick BS, Rothman JE (1987). "Possible role for fatty acyl-coenzyme A in intracellular protein transport". Nature. 326 (6110): 309–312. Bibcode:1987Natur.326..309G. doi:10.1038/326309a0. PMID 3821906. S2CID 4306469.
- ↑ Wan YJ, Cai Y, Cowan C, Magee TR (June 2000). "Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells". Cancer Letters. 154 (1): 19–27. doi:10.1016/s0304-3835(00)00341-4. PMID 10799735.
- ↑ Duncan JA, Gilman AG (June 1998). "A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS)". The Journal of Biological Chemistry. 273 (25): 15830–15837. doi:10.1074/jbc.273.25.15830. PMID 9624183.
- ↑ Berthiaume L, Deichaite I, Peseckis S, Resh MD (March 1994). "Regulation of enzymatic activity by active site fatty acylation. A new role for long chain fatty acid acylation of proteins". The Journal of Biological Chemistry. 269 (9): 6498–6505. doi:10.1016/S0021-9258(17)37399-4. PMID 8120000.
- ↑ Hunt MC, Alexson SE (March 2002). "The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism". Progress in Lipid Research. 41 (2): 99–130. doi:10.1016/s0163-7827(01)00017-0. PMID 11755680.
Further reading
- Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
- Westin MA, Alexson SE, Hunt MC (May 2004). "Molecular cloning and characterization of two mouse peroxisome proliferator-activated receptor alpha (PPARalpha)-regulated peroxisomal acyl-CoA thioesterases". The Journal of Biological Chemistry. 279 (21): 21841–21848. doi:10.1074/jbc.M313863200. PMID 15007068.
- Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, et al. (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–569. doi:10.1038/nbt810. PMID 12665801. S2CID 23783563.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, et al. (June 1995). "Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease". Nature. 375 (6534): 754–760. Bibcode:1995Natur.375..754S. doi:10.1038/375754a0. PMID 7596406. S2CID 4308372.