Document Detail


Metabolomic analysis and identification of a role for the orphan human cytochrome P450 2W1 in selective oxidation of lysophospholipids.
MedLine Citation:
PMID:  22591743     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human cytochrome P450 (P450) 2W1 is still considered an "orphan" because its physiological function is not characterized. To identify its substrate specificity, the purified recombinant enzyme was incubated with colorectal cancer extracts for untargeted substrate searches using an LC/MS-based metabolomic and isotopic labeling approach. In addition to previously reported fatty acids, oleyl (18:1) lysophosphatidylcholine (LPC, lysolecithin) was identified as a substrate for P450 2W1. Other human P450 enzymes tested showed little activity with 18:1 LPC. In addition to the LPCs, P450 2W1 acted on a series of other lysophospholipids, including lysophosphatidylinositol, lysophosphatidylserine, lysophosphatidylglycerol, lysophosphatidylethanolamine, and lysophosphatidic acid but not diacylphospholipids. P450 2W1 utilized sn-1 18:1 LPC as a substrate much more efficiently than the sn-2 isomer; we conclude that the sn-1 isomers of lysophospholipids are preferred substrates. Chiral analysis was performed on the 18:1 epoxidation products and showed enantio-selectivity for formation of (9R,10S) over (9S,10R). [corrected]. The kinetics and position specificities of P450 2W1-catalyzed oxygenation of lysophospholipids (16:0 LPC and 18:1 LPC) and fatty acids (C16:0 and C18:1) were also determined. Epoxidation and hydroxylation of 18:1 LPC are considerably more efficient than for the C18:1 free fatty acid.
Authors:
Yi Xiao; F Peter Guengerich
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-16
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-16     Completed Date:  2012-11-23     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1610-7     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
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MeSH Terms
Descriptor/Qualifier:
Colorectal Neoplasms / metabolism
Cytochrome P-450 Enzyme System / metabolism*
Enzymes
Fatty Acids, Nonesterified / metabolism
Humans
Isomerism
Kinetics
Lysophospholipids / chemistry,  metabolism*
Metabolomics*
Oxidation-Reduction
Substrate Specificity
Grant Support
ID/Acronym/Agency:
P30-ES-000267/ES/NIEHS NIH HHS; R37 CA090426/CA/NCI NIH HHS; R37-CA-090426/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Enzymes; 0/Fatty Acids, Nonesterified; 0/Lysophospholipids; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.-/CYP2W1 protein, human
Comments/Corrections
Erratum In:
J Lipid Res. 2013 May;54(5):1521

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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