ACOT1

Acyl-CoA thioesterase 1 is a protein that in humans is encoded by the ACOT1 gene.^[5]

ACOT1
Identifiers
Aliases	ACOT1, ACH2, CTE-1, LACH2, acyl-CoA thioesterase 1
External IDs	OMIM: 614313; MGI: 2159619; HomoloGene: 134585; GeneCards: ACOT1; OMA:ACOT1 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q24.3 Start 73,537,143 bp[1] End 73,543,796 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12|12 D1 Start 84,098,918 bp[2] End 84,107,176 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad testicle right lobe of liver smooth muscle tissue left ventricle gastrocnemius muscle apex of heart gastric mucosa human kidney right adrenal gland Top expressed in zygote secondary oocyte primary oocyte renal cortex proximal tubule human kidney right kidney salivary gland hair hepatobiliary system More reference expression data BioGPS n/a
Gene ontology Molecular function palmitoyl-CoA hydrolase activity carboxylic ester hydrolase activity hydrolase activity thiolester hydrolase activity acyl-CoA hydrolase activity myristoyl-CoA hydrolase activity Cellular component cytoplasm cytosol Biological process very long-chain fatty acid metabolic process long-chain fatty acid metabolic process acyl-CoA metabolic process fatty acid metabolic process lipid metabolism Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 641371 171281 Ensembl ENSG00000184227 ENSMUSG00000021228 UniProt Q86TX2 Q9QYR7 RefSeq (mRNA) NM_001037161 NM_134246 NM_001346701 RefSeq (protein) NP_001032238 NP_001333630 NP_599007 Location (UCSC) Chr 14: 73.54 – 73.54 Mb Chr 12: 84.1 – 84.11 Mb PubMed search [3] [4]
Wikidata
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Structure

The ACOT1 gene is located on the 14th chromosome, with its specific localization being 14q24.3. It contains 7 exons.^[5]

The protein encoded by this gene contains 410 amino acids, and forms a homodimer with another chain.^[6] 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.^[7]

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.^[8] 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,^[9] hexokinase IV,^[10] 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.^[11] 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.^[12][13][14] Acyl-CoAs also mediate protein targeting to various membranes and regulation of G protein α subunits, because they are substrates for protein acylation.^[15] 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.^[16] 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.^[17]