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Neutral cholesterol ester hydrolase 1 (NCEH) also known as arylacetamide deacetylase-like 1 (AADACL1) or KIAA1363 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 ''NCEH1''
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 ...
. NCEH is an enzyme located in 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 ( ...
. NCEH hydrolyzes 2-acetyl monoalkylglycerol ether, as part of an enzymatic pathway regulating the levels of
platelet activating factor Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
and lysophospholipids that may be involved in cancer development.


Function

The enzymatic reaction catalyzed by NCEH is: * 2-acetyl monoalkylglycerol ether → monoalkylglycerol ether Monoalkylglycerol ethers (MAGEs) can then be converted to lysophospholipids alkyl-
lysophosphatidic acid Lysophosphatidic acid (LPA) is a phospholipid derivative that can act as a signaling molecule. Function LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPAR1, LPAR2, and LPAR3 (also kn ...
(alkyl-LPA) and alkyl-
lysophosphatidylcholine Lysophosphatidylcholines (LPC, lysoPC), also called lysolecithins, are a class of chemical compounds which are derived from phosphatidylcholines. Overview Lysophosphatidylcholines are produced within cells mainly by the enzyme phospholipase ...
(alkyl-LPC). Controversial studies by one group also implicate the protein in the hydrolysis of
cholesterol esters file:Cholesterol oleate.svg, 300px, Cholesterol oleate, a member of the cholesteryl ester family Cholesteryl ester, a dietary lipid, is an ester of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl ...
. However, loss of the protein in mice selectively reduces 2-acetyl monoalkylglycerol ether activity throughout the body.


Clinical significance

Evidence suggests a role for NCEH in cancer. Cancer cell lines contain unusually high levels of the protein. Reduction of the amount of NCEH1 in cancer cells reduces tumor migration and growth in mice and addition of alkyl-LPA restores these processes. NCEH can break down organophosphates like the pesticide metabolite
chlorpyrifos Chlorpyrifos (CPS), also known as Chlorpyrifos ethyl, is an organophosphate pesticide that has been used on crops, animals, and buildings, and in other settings, to kill several pests, including insects and worms. It acts on the nervous systems ...
oxon. Conversely, enzymatic activity can be inhibited by organophosphates.


Structure

NCEH is a
serine hydrolase Serine hydrolases are one of the largest known enzyme classes comprising approximately ~200 enzymes or 1% of the genes in the human proteome. A defining characteristic of these enzymes is the presence of a particular serine at the active site, which ...
that contains an N-terminal transmembrane domain, a central catalytic domain and a lipid-binding domain at its C-terminus. The protein exists in three isoforms that result from differences in
mRNA splicing RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns (non-coding regions of RNA) and ''splicing'' ba ...
. Transcripts encode a protein for isoform a of 448, b of 440 and c of 275
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.


See also

*
Autotaxin Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (E-NPP 2), is an enzyme that in humans is encoded by the ''ENPP2'' gene. Function Autotaxin (ectonucleotide pyrophosphatase/phosphodiesterase 2 (NPP2 or EN ...
*
phosphatidic acid Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty ac ...
*
Lysophospholipid receptor The lysophospholipid receptor (LPL-R) group are members of the G protein-coupled receptor family of integral membrane proteins that are important for lipid signaling. In humans, there are eight LPL receptors Receptor may refer to: *Sensory rec ...
* LPA signaling


References


Further reading

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