ACOT2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesACOT2, CTE-IA, CTE1A, MTE1, PTE2, PTE2A, ZAP128, acyl-CoA thioesterase 2
External IDsOMIM: 609972 MGI: 2159605 HomoloGene: 25661 GeneCards: ACOT2
Orthologs
SpeciesHumanMouse
Entrez

10965

171210

Ensembl

ENSG00000119673

ENSMUSG00000021226

UniProt

P49753

Q9QYR9

RefSeq (mRNA)

NM_006821
NM_001364177
NM_001364178

NM_134188

RefSeq (protein)

NP_006812
NP_001351106
NP_001351107

NP_598949

Location (UCSC)Chr 14: 73.57 – 73.58 MbChr 12: 84.03 – 84.04 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Acyl-CoA thioesterase 2, also known as ACOT2, is an enzyme which in humans is encoded by the ACOT2 gene.[5][6][7]

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.[8] 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.[6]

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.[9] 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,[10] hexokinase IV,[11] 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.[12] 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.[13][14][15] Acyl-CoAs also mediate protein targeting to various membranes and regulation of G Protein α subunits, because they are substrates for protein acylation.[16] 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.[17] 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.[18]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000119673 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021226 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: ACOT2 acyl-CoA thioesterase 2".
  6. 1 2 Jones JM, Gould SJ (Aug 2000). "Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase". Biochemical and Biophysical Research Communications. 275 (1): 233–40. doi:10.1006/bbrc.2000.3285. PMID 10944470.
  7. ↑ Hunt MC, Rautanen A, Westin MA, Svensson LT, Alexson SE (Sep 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): 1855–64. doi:10.1096/fj.06-6042com. PMID 16940157. S2CID 501610.
  8. ↑ Hunt MC, Yamada J, Maltais LJ, Wright MW, Podesta EJ, Alexson SE (Sep 2005). "A revised nomenclature for mammalian acyl-CoA thioesterases/hydrolases". Journal of Lipid Research. 46 (9): 2029–32. doi:10.1194/jlr.E500003-JLR200. PMID 16103133.
  9. ↑ 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 (October 2004). "Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family". Journal of Lipid Research. 45 (10): 1958–61. doi:10.1194/jlr.e400002-jlr200. PMID 15292367.
  10. ↑ Ogiwara, H; Tanabe, T; Nikawa, J; Numa, S (15 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.
  11. ↑ Srere, PA (2 December 1965). "Palmityl-coenzyme A inhibition of the citrate-condensing enzyme". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 106 (3): 445–55. doi:10.1016/0005-2760(65)90061-5. PMID 5881327.
  12. ↑ Gribble, FM; Proks, P; Corkey, BE; Ashcroft, FM (9 October 1998). "Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA". The Journal of Biological Chemistry. 273 (41): 26383–7. doi:10.1074/jbc.273.41.26383. PMID 9756869.
  13. ↑ Nishizuka, Y (April 1995). "Protein kinase C and lipid signaling for sustained cellular responses". FASEB Journal. 9 (7): 484–96. doi:10.1096/fasebj.9.7.7737456. PMID 7737456. S2CID 31065063.
  14. ↑ Glick, BS; Rothman, JE (1987). "Possible role for fatty acyl-coenzyme A in intracellular protein transport". Nature. 326 (6110): 309–12. Bibcode:1987Natur.326..309G. doi:10.1038/326309a0. PMID 3821906. S2CID 4306469.
  15. ↑ Wan, YJ; Cai, Y; Cowan, C; Magee, TR (1 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.
  16. ↑ Duncan, JA; Gilman, AG (19 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): 15830–7. doi:10.1074/jbc.273.25.15830. PMID 9624183.
  17. ↑ Berthiaume, L; Deichaite, I; Peseckis, S; Resh, MD (4 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): 6498–505. doi:10.1016/S0021-9258(17)37399-4. PMID 8120000.
  18. ↑ 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

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