Biology:ACOT4

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Acyl-coenzyme A thioesterase 4 is an enzyme that in humans is encoded by the ACOT4 gene.[1][2][3]

Function

The protein encoded by the ACOT4 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.[4] 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,[5] hexokinase IV,[6] 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.[7] 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.[8][9][10] Acyl-CoAs also mediate protein targeting to various membranes and regulation of G Protein α subunits, because they are substrates for protein acylation.[11] 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.[12] 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.[13]

References

  1. ↑ "A revised nomenclature for mammalian acyl-CoA thioesterases/hydrolases". Journal of Lipid Research 46 (9): 2029–32. Sep 2005. doi:10.1194/jlr.E500003-JLR200. PMID 16103133. 
  2. ↑ "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. Sep 2006. doi:10.1096/fj.06-6042com. PMID 16940157. https://arrow.dit.ie/cgi/viewcontent.cgi?article=1028&context=scschbioart. 
  3. ↑ "Entrez Gene: ACOT4 acyl-CoA thioesterase 4". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=122970. 
  4. ↑ "Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family". Journal of Lipid Research 45 (10): 1958–61. Oct 2004. doi:10.1194/jlr.E400002-JLR200. PMID 15292367. 
  5. ↑ "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. Aug 1978. doi:10.1111/j.1432-1033.1978.tb20893.x. PMID 29756. 
  6. ↑ "Palmityl-coenzyme A inhibition of the citrate-condensing enzyme". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 106 (3): 445–55. Dec 1965. doi:10.1016/0005-2760(65)90061-5. PMID 5881327. 
  7. ↑ "Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA". The Journal of Biological Chemistry 273 (41): 26383–7. Oct 1998. doi:10.1074/jbc.273.41.26383. PMID 9756869. 
  8. ↑ "Protein kinase C and lipid signaling for sustained cellular responses". FASEB Journal 9 (7): 484–96. Apr 1995. doi:10.1096/fasebj.9.7.7737456. PMID 7737456. 
  9. ↑ "Possible role for fatty acyl-coenzyme A in intracellular protein transport". Nature 326 (6110): 309–12. Mar 1987. doi:10.1038/326309a0. PMID 3821906. Bibcode: 1987Natur.326..309G. 
  10. ↑ "Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells". Cancer Letters 154 (1): 19–27. Jun 2000. doi:10.1016/s0304-3835(00)00341-4. PMID 10799735. 
  11. ↑ "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. Jun 1998. doi:10.1074/jbc.273.25.15830. PMID 9624183. 
  12. ↑ "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. Mar 1994. doi:10.1016/S0021-9258(17)37399-4. PMID 8120000. 
  13. ↑ "The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism". Progress in Lipid Research 41 (2): 99–130. Mar 2002. doi:10.1016/s0163-7827(01)00017-0. PMID 11755680. 

External links

Further reading

  • "Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease". Nature 375 (6534): 754–60. Jun 1995. doi:10.1038/375754a0. PMID 7596406. Bibcode: 1995Natur.375..754S. 
  • "Peroxisome proliferator-induced long chain acyl-CoA thioesterases comprise a highly conserved novel multi-gene family involved in lipid metabolism". The Journal of Biological Chemistry 274 (48): 34317–26. Nov 1999. doi:10.1074/jbc.274.48.34317. PMID 10567408. 
  • "Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase". Biochemical and Biophysical Research Communications 275 (1): 233–40. Aug 2000. doi:10.1006/bbrc.2000.3285. PMID 10944470. 
  • "The identification of a succinyl-CoA thioesterase suggests a novel pathway for succinate production in peroxisomes". The Journal of Biological Chemistry 280 (46): 38125–32. Nov 2005. doi:10.1074/jbc.M508479200. PMID 16141203. 




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