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- Arand, M., et al.
(författare)
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The telltale structures of epoxide hydrolases
- 2003
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Ingår i: Drug metabolism reviews (Softcover ed.). - 0360-2532 .- 1097-9883. ; 35:4, s. 365-383
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Tidskriftsartikel (refereegranskat)abstract
- Traditionally, epoxide hydrolases (EH) have been regarded as xenobiotic-metabolizing enzymes implicated in the detoxification of foreign compounds. They are known to play a key role in the control of potentially genotoxic epoxides that arise during metabolism of many lipophilic compounds. Although this is apparently the main function for the mammalian microsomal epoxide hydrolase (mEH), evidence is now accumulating that the mammalian soluble epoxide hydrolase (sEH), despite its proven role in xenobiotic metabolism, also has a central role in the formation and breakdown of physiological signaling molecules. In addition, a certain class of microbial epoxide hydrolases has recently been identified that is an integral part of a catabolic pathway, allowing the use of specific terpens as sole carbon sources. The recently available x-ray structures of a number of EHs mirror their respective functions: the microbial terpen EH differs in its fold from the canonical α/β hydrolase fold of the xenobiotic-metabolizing mammalian EHs. It appears that the latter fold is the perfect solution for the efficient detoxification of a large variety of structurally different epoxides by a single enzyme, whereas the smaller microbial EH, which has a particularly high turnover number with its prefered substrate, seems to be the better solution for the hydrolysis of one specific substrate. The structure of the sEH also includes an additional catalytic domain that has recently been shown to possess phosphatase activity. Although the physiological substrate for this second active site has not been identified so far, the majority of known phosphatases are involved in signaling processes, suggesting that the sEH phosphatase domain also has a role in the regulation of physiological functions.
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- Jiye, A, et al.
(författare)
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Global analysis of low-molecular-weight compounds in human plasma using GC/TOF-MS
- 2004
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Ingår i: DRUG METABOLISM REVIEWS. - 0360-2532. ; 36, s. 246-246
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We developed a method for analysis of low-molecular-weight compounds (LMWC) in human plasma involving extraction of metabolites by organic solvents, derivatization of extract and final analysis by GC/TOF-MS. The overall strategy for the development of the method was based on using design-of-experimental (DOE), and data evaluation based on multivariate statistical tools like PCA and PLS. The results showed that the extraction efficiency for different solvents varied, and that methanol was important for high reproducibility. More than 300 compounds could be detected in one analysis. Forty five of them were identified, including amino acids, lipids and free fatty acids, organic acids, carbohydrates and so on. The quantitative data of these metabolites showed, with two exceptions, high precision and good linearity between response and concentration. By using this method it is now possible to analyze plasma samples with high throughput to identify metabolic biomarkers for different kinds of diseases.
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