期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 341, 期 1, 页码 254-260出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2005.12.180
关键词
soluble epoxide hydrolase; polymorphisms; cholesterol; isoprenylation
资金
- NIEHS NIH HHS [ES011630] Funding Source: Medline
- NIGMS NIH HHS [GM56708] Funding Source: Medline
Soluble epoxide hydrolase (sEH) is highly expressed in human liver and contains a C-terminal epoxide hydrolase activity and an N-terminal phosphatase activity. Endogenous C-terminal hydrolase substrates include arachidonic acid epoxides, however, data are limited regarding possible endogenous substrates for the N-terminal phosphatase. Possible sEH N-terminal substrates include isoprenoid phosphate precursors of cholesterol biosynthesis and protein isoprenylation. Here, we report the kinetic analysis for a range of sEH isoprenoid substrates. We also provide an analysis of the effects of human sEH polymorphisms on isoprenoid hydrolysis. Interestingly, the Arg287Gln polymorphism recently suggested to be involved in hypercholesterolemia was found to possess a higher isoprenoid phosphatase activity than the wild type sEH. Consistent with the finding of isoprenoid phosphates as substrates for sEH, we identified isoprenoid-derived N-terminal inhibitors with IC50 values ranging from 0.84 ( +/- 0.9) to 55.1 (+/- 30.7) mu M. Finally, we evaluated the effects of the different isoprenoid compounds on the C-terminal hydrolase activity. (c) 2006 Elsevier Inc. All rights reserved.
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