Biology:Neutral cholesterol ester hydrolase 1
 Generic protein structure example |
Neutral cholesterol ester hydrolase 1 (NCEH) also known as arylacetamide deacetylase-like 1 (AADACL1) or KIAA1363 is an enzyme that in humans is encoded by the NCEH1 gene.[1]
NCEH is an enzyme located in the endoplasmic reticulum. 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.[2][3]
Function
The enzymatic reaction catalyzed by NCEH is:[2]
- 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.[4] However, loss of the protein in mice selectively reduces 2-acetyl monoalkylglycerol ether activity throughout the body.[3]
Clinical significance
Evidence suggests a role for NCEH in cancer. Cancer cell lines contain unusually high levels of the protein.[5] Reduction of the amount of NCEH1 in cancer cells reduces tumor migration and growth in mice and addition of alkyl-LPA restores these processes.[2]
NCEH can break down organophosphates like the pesticide metabolite chlorpyrifos oxon.[6] Conversely, enzymatic activity can be inhibited by organophosphates.[7]
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.[8] 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.
See also
References
- ↑ "Entrez Gene: Neutral cholesterol ester hydrolase 1". https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=57552.
- ↑ 2.0 2.1 2.2 "An enzyme that regulates ether lipid signaling pathways in cancer annotated by multidimensional profiling". Chemistry & Biology 13 (10): 1041–50. Oct 2006. doi:10.1016/j.chembiol.2006.08.008. PMID 17052608.
- ↑ 3.0 3.1 "Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363". Journal of Lipid Research 51 (10): 2896–908. Oct 2010. doi:10.1194/jlr.M004259. PMID 20625037.
- ↑ "The critical role of neutral cholesterol ester hydrolase 1 in cholesterol removal from human macrophages". Circulation Research 107 (11): 1387–95. Nov 2010. doi:10.1161/CIRCRESAHA.110.226613. PMID 20947831.
- ↑ "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 99 (16): 10335–40. Aug 2002. doi:10.1073/pnas.162187599. PMID 12149457. Bibcode: 2002PNAS...9910335J.
- ↑ "A brain detoxifying enzyme for organophosphorus nerve poisons". Proceedings of the National Academy of Sciences of the United States of America 102 (17): 6195–200. Apr 2005. doi:10.1073/pnas.0501915102. PMID 15840715. Bibcode: 2005PNAS..102.6195N.
- ↑ "Each lipase has a unique sensitivity profile for organophosphorus inhibitors". Toxicological Sciences 91 (1): 166–72. May 2006. doi:10.1093/toxsci/kfj124. PMID 16449251.
- ↑ "Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages". The Journal of Biological Chemistry 283 (48): 33357–64. Nov 2008. doi:10.1074/jbc.M802686200. PMID 18782767.
Further reading
- "Enzyme annotation with chemical tools". Chemistry & Biology 13 (10): 1013–1014. Oct 2006. doi:10.1016/j.chembiol.2006.10.002. PMID 17052604.
- "An enzyme that regulates ether lipid signaling pathways in cancer annotated by multidimensional profiling". Chemistry & Biology 13 (10): 1041–1050. Oct 2006. doi:10.1016/j.chembiol.2006.08.008. PMID 17052608.
- "Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages". The Journal of Biological Chemistry 283 (48): 33357–33364. Nov 2008. doi:10.1074/jbc.M802686200. PMID 18782767.
- "Investigation of low-dose ritonavir on human peripheral blood mononuclear cells using gene expression whole genome microarrays". Genomics 96 (1): 57–65. Jul 2010. doi:10.1016/j.ygeno.2010.03.011. PMID 20353815.
- "The critical role of neutral cholesterol ester hydrolase 1 in cholesterol removal from human macrophages". Circulation Research 107 (11): 1387–1395. Nov 2010. doi:10.1161/CIRCRESAHA.110.226613. PMID 20947831.
 |  |
