Neutral cholesterol ester hydrolase 1 (NCEH) also known as arylacetamide deacetylase-like 1 (AADACL1) or KIAA1363 is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is encoded by the ''NCEH1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. NCEH is an enzyme located in the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

. NCEH hydrolyzes 2-acetyl monoalkylglycerol ether, as part of an enzymatic pathway regulating the levels of platelet activating factor 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 A 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 (a ...

(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. 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, in 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

organophosphate 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 ...

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, whic ...

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. 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 over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

long.

Function

Clinical significance

Structure

See also

References

Further reading