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 NCEH1gene.[1]
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.
↑Igarashi M, Osuga J, Uozaki H, Sekiya M, Nagashima S, Takahashi M, Takase S, Takanashi M, Li Y, Ohta K, Kumagai M, Nishi M, Hosokawa M, Fledelius C, Jacobsen P, Yagyu H, Fukayama M, Nagai R, Kadowaki T, Ohashi K, Ishibashi S (Nov 2010). "The critical role of neutral cholesterol ester hydrolase 1 in cholesterol removal from human macrophages". Circulation Research. 107 (11): 1387–95. doi:10.1161/CIRCRESAHA.110.226613. PMID20947831.
Yilmaz S, Boffito M, Collot-Teixeira S, De Lorenzo F, Waters L, Fletcher C, Back D, Pozniak A, Gazzard B, McGregor JL (Jul 2010). "Investigation of low-dose ritonavir on human peripheral blood mononuclear cells using gene expression whole genome microarrays". Genomics. 96 (1): 57–65. doi:10.1016/j.ygeno.2010.03.011. PMID20353815.
Igarashi M, Osuga J, Uozaki H, Sekiya M, Nagashima S, Takahashi M, Takase S, Takanashi M, Li Y, Ohta K, Kumagai M, Nishi M, Hosokawa M, Fledelius C, Jacobsen P, Yagyu H, Fukayama M, Nagai R, Kadowaki T, Ohashi K, Ishibashi S (Nov 2010). "The critical role of neutral cholesterol ester hydrolase 1 in cholesterol removal from human macrophages". Circulation Research. 107 (11): 1387–1395. doi:10.1161/CIRCRESAHA.110.226613. PMID20947831.