ACOT2

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Acyl-CoA thioesterase 2
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ACOT2 ; CTE-IA; CTE1A; MTE1; PTE2; PTE2A; ZAP128
External IDs OMIM609972 MGI2159605 HomoloGene25661 GeneCards: ACOT2 Gene
EC number 3.1.2.2
RNA expression pattern
PBB GE ACOT2 202982 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 10965 171210
Ensembl ENSG00000119673 ENSMUSG00000021226
UniProt P49753 Q9QYR9
RefSeq (mRNA) NM_006821 NM_134188
RefSeq (protein) NP_006812 NP_598949
Location (UCSC) Chr 14:
73.57 – 73.58 Mb
Chr 12:
83.99 – 83.99 Mb
PubMed search [1] [2]

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[edit]

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[edit]

  1. ^ "Entrez Gene: ACOT2 acyl-CoA thioesterase 2". 
  2. ^ a b 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. PMID 15292367. 
  6. ^ 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 / FEBS 89 (1): 33–41. PMID 29756. 
  7. ^ Srere, PA (2 December 1965). "Palmityl-coenzyme A inhibition of the citrate-condensing enzyme.". Biochimica et biophysica acta 106 (3): 445–55. PMID 5881327. 
  8. ^ 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. PMID 9756869. 
  9. ^ Nishizuka, Y (April 1995). "Protein kinase C and lipid signaling for sustained cellular responses.". FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 (7): 484–96. PMID 7737456. 
  10. ^ Glick, BS; Rothman, JE. "Possible role for fatty acyl-coenzyme A in intracellular protein transport.". Nature 326 (6110): 309–12. PMID 3821906. 
  11. ^ 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. PMID 10799735. 
  12. ^ 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. PMID 9624183. 
  13. ^ 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. PMID 8120000. 
  14. ^ 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. PMID 11755680. 

Further reading[edit]

  • 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. 
  • 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. 
  • 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. 
  • 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): 21841–8. 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): 566–9. doi:10.1038/nbt810. PMID 12665801. 
  • 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. 
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
  • Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
  • Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M et al. (Jun 1995). "Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease". Nature 375 (6534): 754–60. doi:10.1038/375754a0. PMID 7596406.