Document Detail


CYP2U1, a novel human thymus- and brain-specific cytochrome P450, catalyzes omega- and (omega-1)-hydroxylation of fatty acids.
MedLine Citation:
PMID:  14660610     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Long chain fatty acids have recently emerged as critical signaling molecules in neuronal, cardiovascular, and renal processes, yet little is presently known about the precise mechanisms controlling their tissue distribution and bioactivation. We have identified a novel cytochrome P450, CYP2U1, which may play an important role in modulating the arachidonic acid signaling pathway. Northern blot and real-time PCR analysis demonstrated that CYP2U1 transcripts were most abundant in the thymus and the brain (cerebellum), indicating a specific physiological role for CYP2U1 in these tissues. Recombinant human CYP2U1 protein, expressed in baculovirus-infected Sf9 insect cells, was found to metabolize arachidonic acid exclusively to two region-specific products as determined by liquid chromatography-mass spectrometry. These metabolites were identified as 19- and 20-hydroxy-modified arachidonic acids by liquid chromatography-tandem mass spectrometry analysis. In addition to omega/omega-1 hydroxylation of arachidonic acid, CYP2U1 protein also catalyzed the hydroxylation of structurally related long chain fatty acid (docosahexaenoic acid) but not fatty acids such as lauric acid or linoleic acid. This is the first report of the cloning and functional expression of a new human member of P450 family 2, CYP2U1, which metabolizes long chain fatty acids. Based on the ability of CYP2U1 to generate bioactive eicosanoid derivatives, we postulate that CYP2U1 plays an important physiological role in fatty acid signaling processes in both cerebellum and thymus.
Authors:
Samuel S Chuang; Christian Helvig; Mohammed Taimi; Heather A Ramshaw; Andrew H Collop; Ma'an Amad; Jay A White; Martin Petkovich; Glenville Jones; Bozena Korczak
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-12-03
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-17     Completed Date:  2004-04-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6305-14     Citation Subset:  IM    
Affiliation:
Cytochroma, Inc, Markham, Ontario L3R 8E4, Canada.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AY343323
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MeSH Terms
Descriptor/Qualifier:
Alkane 1-Monooxygenase / metabolism*
Amino Acid Sequence
Animals
Arachidonic Acids / metabolism
Baculoviridae
Base Sequence
Blotting, Western
Brain / enzymology*
Catalysis
Cell Line
Chromatography, Liquid
Cytochrome P-450 Enzyme System / biosynthesis*,  chemistry*
DNA, Complementary / metabolism
Expressed Sequence Tags
Fatty Acids / chemistry*
Humans
Hydroxyeicosatetraenoic Acids / chemistry
Immunoblotting
Insects
Mass Spectrometry
Microsomes / metabolism
Mixed Function Oxygenases / biosynthesis*,  chemistry*
Molecular Sequence Data
Multigene Family
Phylogeny
Protein Structure, Tertiary
RNA, Messenger / metabolism
Recombinant Proteins / chemistry,  metabolism
Signal Transduction
Substrate Specificity
Thymus Gland / enzymology*,  metabolism
Time Factors
Tissue Distribution
alpha-Linolenic Acid / chemistry
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/DNA, Complementary; 0/Fatty Acids; 0/Hydroxyeicosatetraenoic Acids; 0/RNA, Messenger; 0/Recombinant Proteins; 463-40-1/alpha-Linolenic Acid; 79551-85-2/19-hydroxy-5,8,11,14-eicosatetraenoic acid; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/CYP2U1 protein, human; EC 1.-/Mixed Function Oxygenases; EC 1.14.15.3/Alkane 1-Monooxygenase

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


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