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Thioesterases are enzymes which belong to the
esterase An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis. A wide range of different esterases exist that differ in their substrate specificity, their protein structure, ...
family. Esterases, in turn, are one type of the several
hydrolases Hydrolase is a class of enzyme that commonly perform as biochemical catalysts that use water to break a chemical bond, which typically results in dividing a larger molecule into smaller molecules. Some common examples of hydrolase enzymes are este ...
known. Thioesterases exhibit esterase activity (splitting of an
ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
into
acid In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
and
alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...
, in the presence of water) specifically at a
thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...
group. Thioesterases or thiolester hydrolases are identified as members of EC 3.1.2.


Family

The thioesterase activity is performed by members of the
acyl-CoA Acyl-CoA is a group of coenzymes that metabolize fatty acids. Acyl-CoA's are susceptible to beta oxidation, forming, ultimately, acetyl-CoA. The acetyl-CoA enters the citric acid cycle, eventually forming several equivalents of ATP. In this way ...
thioesterase (ACOT) family. The regulatory role of ACOT in
fatty acid metabolism Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes ...
depends on their substrate specificity, tissue expression and subcellular localization. For example, deactivation of
fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
s at the ER may traffic fatty acids away from pathways associated with the ER membrane, such as
glycerolipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and o ...
biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
. Two structurally different ACOT types lead to a similar
enzymatic Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
activity
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
, dividing the family into type I and type II ACOTs. Type I ACOTs (ACOT1–6) contain the α/β-hydrolase domain, which is also present in many lipases and esterases . Type II ACOTs (ACOT7–15) have a characteristic structural motif called the ‘Hotdog fold’ domain .


Examples

Acetyl-CoA hydrolase, palmitoyl-CoA hydrolase, succinyl-CoA hydrolase, formyl-CoA hydrolase, acyl-CoA hydrolase are a few examples of this group of enzymes.
Ubiquitin thiolesterase Ubiquitin carboxy-terminal hydrolase L1 (, ''ubiquitin C-terminal hydrolase'', ''UCH-L1'') is a deubiquitinating enzyme. Function UCH-L1 is a member of a gene family whose products hydrolyze small C-terminal adducts of ubiquitin to generate ...
is a well-known example, whose structure has been analyzed. Humans genes which encode thioesterases include:
ACOT1 Acyl-CoA thioesterase 1 is a protein that in humans is encoded by the ACOT1 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 con ...
,
ACOT2 Acyl-CoA thioesterase 2, also known as ACOT2, is an enzyme which in humans is encoded by the ''ACOT2'' gene. Acyl-CoA thioesterases, such as ACOT2, are a group of enzymes that hydrolyze Coenzyme A (CoA) esters, such as acyl-CoAs, bile CoAs, and ...
,
ACOT4 Acyl-coenzyme A thioesterase 4 is an enzyme that in humans is encoded by the ''ACOT4'' gene. 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 est ...
,
ACOT6 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. Function The protein encoded by the ACOT1 gene is part of a family of Acyl-CoA ...
, ACOT7,
ACOT8 Acyl-coenzyme A thioesterase 8 is an enzyme that in humans is encoded by the ''ACOT8'' gene. The protein encoded by this gene is a peroxisomal thioesterase that appears to be involved more in the oxidation of fatty acids rather than in their form ...
,
ACOT9 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 ...
,
ACOT11 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 ...
(STARD14),
ACOT12 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 In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe th ...
(STARD15), OLAH,
PPT1 Palmitoyl-protein thioesterase 1 (PPT-1), also known as palmitoyl-protein hydrolase 1, is an enzyme that in humans is encoded by the PPT1 gene. Function PPT-1 a member of the palmitoyl protein thioesterase family. PPT-1 is a small glycoprotei ...
, PPT2, THEM2 (ACOT13), THEM4, THEM4P1, THEM5


References


External links

* * Peripheral membrane proteins {{enzyme-stub