Neutral cholesterol ester hydrolase 1

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 (alkyl-LPA) and alkyl-lysophosphatidylcholine (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 oxon. Conversely, enzymatic activity can be inhibited by organophosphates.

Structure

NCEH is a serine hydrolase 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 long.

References

References

1. "Entrez Gene: Neutral cholesterol ester hydrolase 1".
2. (Oct 2006). "An enzyme that regulates ether lipid signaling pathways in cancer annotated by multidimensional profiling". Chemistry & Biology.
3. (Oct 2010). "Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363". Journal of Lipid Research.
4. (Nov 2010). "The critical role of neutral cholesterol ester hydrolase 1 in cholesterol removal from human macrophages". Circulation Research.
5. (Aug 2002). "Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness". Proceedings of the National Academy of Sciences of the United States of America.
6. (Apr 2005). "A brain detoxifying enzyme for organophosphorus nerve poisons". Proceedings of the National Academy of Sciences of the United States of America.
7. (May 2006). "Each lipase has a unique sensitivity profile for organophosphorus inhibitors". Toxicological Sciences.
8. (Nov 2008). "Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages". The Journal of Biological Chemistry.