Source:http://linkedlifedata.com/resource/pubmed/id/15358094
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2004-9-10
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pubmed:abstractText |
The metabolism of 1alpha,25(OH)(2)D(3) (1alpha,3beta) and its A-ring diastereomers, 1beta,25(OH)(2)D(3) (1beta,3beta), 1alpha,25(OH)(2)-3-epi-D(3) (1alpha,3alpha), and 1beta,25(OH)(2)-3-epi-D(3) (1beta,3alpha), was examined to compare the substrate specificity and reaction specificity of CYP24A1 between humans and rats. The ratio between C-23 and C-24 oxidation pathways in human CYP24A1-dependent metabolism of (1alpha,3alpha) and (1beta,3alpha) was 1:1, although the ratio for (1alpha,3beta) and (1beta,3beta) was 1:4. These results indicate that the orientation of the hydroxyl group at the C-3 position determines the ratio between C-23 and C-24 oxidation pathways. A remarkable increase of metabolites in the C-23 oxidation pathway was also observed in rat CYP24A1-dependent metabolism. The binding affinity of human CYP24A1 for A-ring diastereomers was (1alpha,3beta)>(1alpha,3alpha)>(1beta,3beta)>(1beta,3alpha), indicating that both hydroxyl groups at C-1 and C-3 positions significantly affect substrate-binding. The information obtained in this study is quite useful for understanding substrate recognition of CYP24A1 and designing new vitamin D analogs.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcitriol,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/vitamin D 24-hydroxylase
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
321
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
774-82
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pubmed:dateRevised |
2008-8-16
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pubmed:meshHeading |
pubmed-meshheading:15358094-Animals,
pubmed-meshheading:15358094-Calcitriol,
pubmed-meshheading:15358094-Chromatography, High Pressure Liquid,
pubmed-meshheading:15358094-Cytochrome P-450 Enzyme System,
pubmed-meshheading:15358094-Humans,
pubmed-meshheading:15358094-Hydroxylation,
pubmed-meshheading:15358094-Isomerism,
pubmed-meshheading:15358094-Kinetics,
pubmed-meshheading:15358094-Mass Spectrometry,
pubmed-meshheading:15358094-Oxidation-Reduction,
pubmed-meshheading:15358094-Rats,
pubmed-meshheading:15358094-Recombinant Proteins,
pubmed-meshheading:15358094-Species Specificity,
pubmed-meshheading:15358094-Stereoisomerism,
pubmed-meshheading:15358094-Steroid Hydroxylases,
pubmed-meshheading:15358094-Substrate Specificity
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pubmed:year |
2004
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pubmed:articleTitle |
Metabolism of A-ring diastereomers of 1alpha,25-dihydroxyvitamin D3 by CYP24A1.
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pubmed:affiliation |
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa, Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
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pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro,
Research Support, Non-U.S. Gov't
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