ACOT1

Acyl-CoA thioesterase 1 is a is_associated_with::protein that in humans is encoded by the ACOT1 is_associated_with::gene.

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. The protein contains a is_associated_with::StAR-related transfer domain, which is a domain responsible for binding to lipids. There are 4 known ligands that bind to this homodimer: is_associated_with::polyethylene glycol, is_associated_with::chlorine, is_associated_with::glycerol, and a form of is_associated_with::TCEP.

Function
The protein encoded by the ACOT1 gene is part of a family of is_associated_with::Acyl-CoA is_associated_with::thioesterases, which catalyze the is_associated_with::hydrolysis of various is_associated_with::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 is_associated_with::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. 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 is_associated_with::allosteric regulation of enzymes such as is_associated_with::acetyl-CoA carboxylase, is_associated_with::hexokinase IV, and the citrate condensing enzyme. Long-chain acyl-CoAs also regulate opening of is_associated_with::ATP-sensitive potassium channels and activation of is_associated_with::Calcium ATPases, thereby regulating is_associated_with::insulin secretion. A number of other cellular events are also mediated via acyl-CoAs, for example signal transduction through is_associated_with::protein kinase C, inhibition of is_associated_with::retinoic acid-induced apoptosis, and involvement in budding and fusion of the is_associated_with::endomembrane system. Acyl-CoAs also mediate protein targeting to various membranes and regulation of is_associated_with::G Protein α subunits, because they are substrates for protein acylation. In the is_associated_with::mitochondria, acyl-CoA esters are involved in the acylation of mitochondrial NAD+ dependent is_associated_with::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 is_associated_with::NADH/NAD+ ratio in order to maintain optimal mitochondrial is_associated_with::beta oxidation of fatty acids. The role of CoA esters in is_associated_with::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.