ACOT1

{{Short description|Protein-coding gene in the species Homo sapiens}}

Acyl-CoA thioesterase 1 is a protein that in humans is encoded by the ACOT1 gene.{{cite web | title = Entrez Gene: Acyl-CoA thioesterase 1 | url = https://www.ncbi.nlm.nih.gov/gene/641371 }}

Structure

The ACOT1 gene is located on the 14th chromosome, with its specific localization being 14q24.3. It contains 7 exons.

The protein encoded by this gene contains 410 amino acids, and forms a homodimer with another chain.{{cite web|title=Model Results|url=http://swissmodel.expasy.org/repository/smr.php?sptr_ac=Q86TX2&csm=04675F28D9D53B97|website=SwissProt|access-date=21 May 2015}}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }} The protein contains a StAR-related transfer domain, which is a domain responsible for binding to lipids. There are 4 known ligands that bind to this homodimer: polyethylene glycol, chlorine, glycerol, and a form of TCEP.{{cite journal | vauthors = Thorsell AG, Lee WH, Persson C, Siponen MI, Nilsson M, Busam RD, Kotenyova T, Schüler H, Lehtiö L | title = Comparative structural analysis of lipid binding START domains | journal = PLOS ONE | volume = 6 | issue = 6 | pages = e19521 | pmid = 21738568 | doi = 10.1371/journal.pone.0019521 | year=2011 | pmc=3127847| bibcode = 2011PLoSO...619521T | doi-access = free }}

Function

The protein encoded by the ACOT1 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.{{cite journal | vauthors = 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 | title = Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family | journal = Journal of Lipid Research | volume = 45 | issue = 10 | pages = 1958–61 | date = Oct 2004 | pmid = 15292367 | doi = 10.1194/jlr.E400002-JLR200 | doi-access = free }} 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,{{cite journal | vauthors = Ogiwara H, Tanabe T, Nikawa J, Numa S | title = Inhibition of rat-liver acetyl-coenzyme-A carboxylase by palmitoyl-coenzyme A. Formation of equimolar enzyme-inhibitor complex | journal = European Journal of Biochemistry | volume = 89 | issue = 1 | pages = 33–41 | date = Aug 1978 | pmid = 29756 | doi=10.1111/j.1432-1033.1978.tb20893.x}} hexokinase IV,{{cite journal | vauthors = Srere PA | title = Palmityl-coenzyme A inhibition of the citrate-condensing enzyme | journal = Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | volume = 106 | issue = 3 | pages = 445–55 | date = Dec 1965 | pmid = 5881327 | doi=10.1016/0005-2760(65)90061-5}} 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.{{cite journal | vauthors = Gribble FM, Proks P, Corkey BE, Ashcroft FM | title = Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA | journal = The Journal of Biological Chemistry | volume = 273 | issue = 41 | pages = 26383–7 | date = Oct 1998 | pmid = 9756869 | doi=10.1074/jbc.273.41.26383| doi-access = free }} 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.{{cite journal | vauthors = Nishizuka Y | title = Protein kinase C and lipid signaling for sustained cellular responses | journal = FASEB Journal | volume = 9 | issue = 7 | pages = 484–96 | date = Apr 1995 | pmid = 7737456 | doi=10.1096/fasebj.9.7.7737456| doi-access = free | s2cid = 31065063 }}{{cite journal | vauthors = Glick BS, Rothman JE | title = Possible role for fatty acyl-coenzyme A in intracellular protein transport | journal = Nature | volume = 326 | issue = 6110 | pages = 309–12 | date = Mar 1987 | pmid = 3821906 | doi = 10.1038/326309a0 | bibcode = 1987Natur.326..309G | s2cid = 4306469 }}{{cite journal | vauthors = Wan YJ, Cai Y, Cowan C, Magee TR | title = Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells | journal = Cancer Letters | volume = 154 | issue = 1 | pages = 19–27 | date = Jun 2000 | pmid = 10799735 | doi=10.1016/s0304-3835(00)00341-4}} Acyl-CoAs also mediate protein targeting to various membranes and regulation of G protein α subunits, because they are substrates for protein acylation.{{cite journal | vauthors = Duncan JA, Gilman AG | title = A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS) | journal = The Journal of Biological Chemistry | volume = 273 | issue = 25 | pages = 15830–7 | date = Jun 1998 | pmid = 9624183 | doi=10.1074/jbc.273.25.15830| doi-access = free }} 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.{{cite journal | vauthors = Berthiaume L, Deichaite I, Peseckis S, Resh MD | title = Regulation of enzymatic activity by active site fatty acylation. A new role for long chain fatty acid acylation of proteins | journal = The Journal of Biological Chemistry | volume = 269 | issue = 9 | pages = 6498–505 | date = Mar 1994 | doi = 10.1016/S0021-9258(17)37399-4 | pmid = 8120000 | doi-access = free }} 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.{{cite journal | vauthors = Hunt MC, Alexson SE | title = The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism | journal = Progress in Lipid Research | volume = 41 | issue = 2 | pages = 99–130 | date = Mar 2002 | pmid = 11755680 | doi=10.1016/s0163-7827(01)00017-0}}

References

External links

{{UCSC gene info|ACOT1}}
{{PDBe-KB2|Q86TX2|Acyl-coenzyme A thioesterase 1}}

ACOT1

Structure

Function

References

External links

Further reading