| ACOT1 | |||||||||||||||||||||||||
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| Aliases | ACOT1 , ACH2, CTE-1, LACH2, acyl-CoA thioesterase 1 | ||||||||||||||||||||||||
| External IDs | OMIM: 614313 MGI: 2159619 HomoloGene: 134585 GeneCards: ACOT1 | ||||||||||||||||||||||||
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| Orthologs | |||||||||||||||||||||||||
| Species | Human | Mouse | |||||||||||||||||||||||
| Entrez | |||||||||||||||||||||||||
| Ensembl | |||||||||||||||||||||||||
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| RefSeq (mRNA) | |||||||||||||||||||||||||
| RefSeq (protein) | |||||||||||||||||||||||||
| Location (UCSC) | Chr 14: 73.54 – 73.54 Mb | n/a | |||||||||||||||||||||||
| PubMed search | [2] | [3] | |||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||
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Acyl-CoA thioesterase 1 is a protein that in humans is encoded by the ACOT1 gene. [4]
The ACOT1 gene is located on the 14th chromosome, with its specific localization being 14q24.3. It contains 7 exons. [4]
The protein encoded by this gene contains 410 amino acids, and forms a homodimer with another chain. [5] 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. [6]
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. [7] 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, [8] hexokinase IV, [9] 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. [10] 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. [11] [12] [13] Acyl-CoAs also mediate protein targeting to various membranes and regulation of G protein α subunits, because they are substrates for protein acylation. [14] 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. [15] 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. [16]
Thioesterases are enzymes which belong to the esterase family. Esterases, in turn, are one type of the several hydrolases known.
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,
In enzymology, a palmitoyl-CoA hydrolase 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 respective thiol.
In enzymology, a [acyl-carrier-protein] S-malonyltransferase is an enzyme that catalyzes the chemical reaction
Sterol O-acyltransferase is an intracellular protein located in the endoplasmic reticulum that forms cholesteryl esters from cholesterol.
Long-chain-fatty-acid—CoA ligase 1 is an enzyme that in humans is encoded by the ACSL1 gene.
Acyl-coenzyme A thioesterase 8 is an enzyme that in humans is encoded by the ACOT8 gene.
Long-chain-fatty-acid—CoA ligase 5 is an enzyme that in humans is encoded by the ACSL5 gene.
Long-chain-fatty-acid—CoA ligase 3 is an enzyme that in humans is encoded by the ACSL3 gene.
Long-chain-fatty-acid—CoA ligase 4 is an enzyme that in humans is encoded by the ACSL4 gene.
Acyl-CoA thioesterase 2, also known as ACOT2, is an enzyme which in humans is encoded by the ACOT2 gene.
Very long-chain acyl-CoA synthetase is an enzyme that in humans is encoded by the SLC27A2 gene.
Cytosolic acyl coenzyme A thioester hydrolase is an enzyme that in humans is encoded by the ACOT7 gene.
Acyl-coenzyme A thioesterase 4 is an enzyme that in humans is encoded by the ACOT4 gene.
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.
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.
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.
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.
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.
Acyl-CoA synthetase short-chain family member 3 is a protein that in humans is encoded by the ACSS3 gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
