Liver carboxylesterase 1 also known as carboxylesterase 1 (CES1, hCE-1 or CES1A1) is an

enzyme 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 ...

that in humans is encoded by the ''CES1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. The protein is also historically known as

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

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, ...

1 (SES1),

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...

esterase and cholesterol

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 ...

hydrolase 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 ...

(CEH). Three transcript variants encoding three different isoforms have been found for this gene. The various protein products from isoform a, b and c range in size from 568, 567 and 566

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

long, respectively. CES1 is present in most tissues with higher levels in the liver and low levels in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...

Function

Carboxylesterase 1 is a serine esterase and member of a large multigene

carboxylesterase The enzyme carboxylesterase (or carboxylic-ester hydrolase, EC 3.1.1.1; systematic name carboxylic-ester hydrolase) catalyzes reactions of the following form: :a carboxylic ester + H2O \rightleftharpoons an alcohol + a carboxylate Most enzymes fr ...

family. It is also part of the alpha/beta fold hydrolase family. These enzymes are responsible for the hydrolysis of ester- and

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

-bond-containing

xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...

s and drugs such as cocaine and heroin. They also hydrolyze long-chain fatty acid esters and

thioesters In organic chemistry, thioesters are organosulfur compounds with the functional group . They are analogous to carboxylate esters () with the sulfur in the thioester playing the role of the linking oxygen in the carboxylate ester, as implied by ...

. As part of

phase II metabolism Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...

, the resulting carboxylates are then often conjugated by other enzymes to increase solubility and eventually excreted. This enzyme is known to hydrolyze aromatic and aliphatic esters and can manage cellular cholesterol esterification levels. It may also play a role in detoxification in the lung and/or protection of the central nervous system from ester or amide compounds. The protein contains an amino acid sequence at its N-terminus that sends it into the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

where a C-terminal sequence can bind to a KDEL receptor.

Clinical significance

Carboxylesterase 1 deficiency may be associated with

non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness. ...

or B-cell lymphocytic leukemia. Inhibition of CES1 by in particular

organophosphates In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

reduces tumor-killing activity by monocytes. The loss of this protein in monocytes is one product of

organophosphate poisoning Organophosphate poisoning is poisoning due to organophosphates (OPs). Organophosphates are used as insecticides, medications, and nerve agents. Symptoms include increased saliva and tear production, diarrhea, vomiting, small pupils, sweating, mus ...

. CES1 can activate or deactivate various drugs. CES1 is responsible for the activation of many prodrugs such as angiotensin-converting enzyme (ACE) inhibitors, oseltamivir, and dabigatran. Genetic variants of CES1 can significantly affect both pharmaocokinetics and pharmacodynamics of drugs metabolized by CES1, such as

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, ...

and

clopidogrel Clopidogrel — sold under the brand name Plavix, among others — is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following t ...

. The ability of CES1 to metabolize heroin and cocaine among other drugs has suggested a therapeutic role for the enzyme.

Function

Clinical significance

Interactive pathway map

References

Further reading