Source:http://linkedlifedata.com/resource/pubmed/id/11997390
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
28
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pubmed:dateCreated |
2002-7-8
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pubmed:abstractText |
Postabsorptive elimination of the various forms of vitamin E appears to play a key role in regulation of tissue tocopherol concentrations, but mechanisms of tocopherol metabolism have not been elucidated. Here we describe a pathway involving cytochrome P450-mediated omega-hydroxylation of the tocopherol phytyl side chain followed by stepwise removal of two- or three-carbon moieties, ultimately yielding the 3'-carboxychromanol metabolite that is excreted in urine. All key intermediates of gamma-tocopherol metabolism via this pathway were identified in hepatocyte cultures using gas chromatography-mass spectrometry. NADPH-dependent synthesis of the initial gamma- and alpha-tocopherol 13'-hydroxy and -carboxy metabolites was demonstrated in rat and human liver microsomes. Functional analysis of several recombinant human liver P450 enzymes revealed that tocopherol-omega-hydroxylase activity was associated only with CYP4F2, which also catalyzes omega-hydroxylation of leukotriene B(4) and arachidonic acid. Tocopherol-omega-hydroxylase exhibited similar binding affinities but markedly higher catalytic activities for gamma-tocopherol than alpha-tocopherol, suggesting a role for this pathway in the preferential physiological retention of alpha-tocopherol and elimination of gamma-tocopherol. Sesamin potently inhibited tocopherol-omega-hydroxylase activity exhibited by CYP4F2 and rat or human liver microsomes. Since dietary sesamin also results in elevated tocopherol levels in vivo, this pathway appears to represent a functionally significant means of regulating vitamin E status.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases,
http://linkedlifedata.com/resource/pubmed/chemical/Tocopherols,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin E,
http://linkedlifedata.com/resource/pubmed/chemical/cytochrome P-450 omega-hydroxylase
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25290-6
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11997390-Animals,
pubmed-meshheading:11997390-Chromatography, High Pressure Liquid,
pubmed-meshheading:11997390-Cytochrome P-450 Enzyme System,
pubmed-meshheading:11997390-Gas Chromatography-Mass Spectrometry,
pubmed-meshheading:11997390-Humans,
pubmed-meshheading:11997390-Hydroxylation,
pubmed-meshheading:11997390-Microsomes, Liver,
pubmed-meshheading:11997390-Mixed Function Oxygenases,
pubmed-meshheading:11997390-Rats,
pubmed-meshheading:11997390-Substrate Specificity,
pubmed-meshheading:11997390-Tocopherols,
pubmed-meshheading:11997390-Vitamin E
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pubmed:year |
2002
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pubmed:articleTitle |
Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status.
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pubmed:affiliation |
Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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