ACOT2

Last updated
ACOT2
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ACOT2 , CTE-IA, CTE1A, MTE1, PTE2, PTE2A, ZAP128, acyl-CoA thioesterase 2
External IDs OMIM: 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 Mb Chr 12: 84.03 – 84.04 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Contents

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]

Related Research Articles

Thioesterases are enzymes which belong to the esterase family. Esterases, in turn, are one type of the several hydrolases known.

<span class="mw-page-title-main">Long-chain-fatty-acid—CoA ligase</span> Class of enzymes

The long chain fatty acyl-CoA ligase is an enzyme of the ligase family that activates the oxidation of complex fatty acids. Long chain fatty acyl-CoA synthetase catalyzes the formation of fatty acyl-CoA by a two-step process proceeding through an adenylated intermediate. The enzyme catalyzes the following reaction,

The enzyme choloyl-CoA hydrolase (EC 3.1.2.27) catalyzes the reaction

Palmitoyl-CoA hydrolase (EC 3.1.2.2) is an enzyme in the family of hydrolases that specifically acts on thioester bonds. It catalyzes the hydrolysis of long chain fatty acyl thioesters of acyl carrier protein or coenzyme A to form free fatty acid and the corresponding thiol:

<span class="mw-page-title-main">Palmitoyl(protein) hydrolase</span>

Palmitoyl protein hydrolase/thioesterases is an enzyme (EC 3.1.2.22) that removes thioester-linked fatty acyl groups such as palmitate from modified cysteine residues in proteins or peptides during lysosomal degradation. It catalyzes the reaction

Sterol O-acyltransferase is an intracellular protein located in the endoplasmic reticulum that forms cholesteryl esters from cholesterol.

<span class="mw-page-title-main">ACOX1</span> Protein-coding gene in the species Homo sapiens

Peroxisomal acyl-coenzyme A oxidase 1 is an enzyme that in humans is encoded by the ACOX1 gene.

<span class="mw-page-title-main">ACSL1</span> Protein-coding gene in the species Homo sapiens

Long-chain-fatty-acid—CoA ligase 1 is an enzyme that in humans is encoded by the ACSL1 gene.

<span class="mw-page-title-main">ACOT8</span> Protein-coding gene in the species Homo sapiens

Acyl-coenzyme A thioesterase 8 is an enzyme that in humans is encoded by the ACOT8 gene.

<span class="mw-page-title-main">ACSL3</span> Protein-coding gene in the species Homo sapiens

Long-chain-fatty-acid—CoA ligase 3 is an enzyme that in humans is encoded by the ACSL3 gene.

<span class="mw-page-title-main">Very long-chain acyl-CoA synthetase</span> Protein-coding gene in the species Homo sapiens

Very long-chain acyl-CoA synthetase is an enzyme that in humans is encoded by the SLC27A2 gene.

<span class="mw-page-title-main">ACOT7</span> Protein-coding gene in the species Homo sapiens

Cytosolic acyl coenzyme A thioester hydrolase is an enzyme that in humans is encoded by the ACOT7 gene.

<span class="mw-page-title-main">ACOT4</span> Protein-coding gene in the species Homo sapiens

Acyl-coenzyme A thioesterase 4 is an enzyme that in humans is encoded by the ACOT4 gene.

<span class="mw-page-title-main">ACOT11</span> Protein-coding gene in the species Homo sapiens

Acyl-coenzyme A thioesterase 11 also known as StAR-related lipid transfer protein 14 (STARD14) is an enzyme that in humans is encoded by the ACOT11 gene. This gene encodes a protein with acyl-CoA thioesterase activity towards medium (C12) and long-chain (C18) fatty acyl-CoA substrates which relies on its StAR-related lipid transfer domain. Expression of a similar murine protein in brown adipose tissue is induced by cold exposure and repressed by warmth. Expression of the mouse protein has been associated with obesity, with higher expression found in obesity-resistant mice compared with obesity-prone mice. Alternative splicing results in two transcript variants encoding different isoforms.

<span class="mw-page-title-main">ACOT12</span> Protein-coding gene in the species Homo sapiens

Acyl-coenzyme A thioesterase 12 or StAR-related lipid transfer protein 15 (STARD15) is an enzyme that in humans is encoded by the ACOT12 gene. The protein contains a StAR-related lipid transfer domain.

<span class="mw-page-title-main">ACOT6</span> Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 6 is a protein that in humans is encoded by the ACOT6 gene. The protein, also known as C14orf42, is an enzyme with thioesterase activity.

Monolysocardiolipin acyltransferase is a mitochondrial acyltransferase that facilitates the remodeling of monolysocardiolipin (MLCL) into cardiolipin.

<span class="mw-page-title-main">Acyl-CoA thioesterase 9</span> Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 9 is a protein that is encoded by the human ACOT9 gene. It is a member of the acyl-CoA thioesterase superfamily, which is a group of enzymes that hydrolyze Coenzyme A esters. There is no known function, however it has been shown to act as a long-chain thioesterase at low concentrations, and a short-chain thioesterase at high concentrations.

<span class="mw-page-title-main">ACOT13</span> Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 13 is a protein that in humans is encoded by the ACOT13 gene. This gene encodes a member of the thioesterase superfamily. In humans, the protein co-localizes with microtubules and is essential for sustained cell proliferation.

<span class="mw-page-title-main">ACOT1</span> Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 1 is a protein that in humans is encoded by the ACOT1 gene.

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.

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