Source:http://linkedlifedata.com/resource/pubmed/id/15078099
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
15
|
| pubmed:dateCreated |
2004-4-13
|
| pubmed:abstractText |
Our previous study revealed that human CYP24A1 catalyzes a remarkable metabolism consisting of both C-23 and C-24 hydroxylation pathways that used both 25(OH)D(3) and 1alpha,25(OH)(2)D(3) as substrates, while rat CYP24A1 showed extreme predominance of the C-24 over C-23 hydroxylation pathway [Sakaki, T., Sawada, N., Komai, K., Shiozawa, S., Yamada, S., Yamamoto, K., Ohyama, Y. and Inouye, K. (2000) Eur. J. Biochem. 267, 6158-6165]. In this study, by using the Escherichia coli expression system for human CYP24A1, we identified 25,26,27-trinor-23-ene-D(3) and 25,26,27-trinor-23-ene-1alpha(OH)D(3) as novel metabolites of 25(OH)D(3) and 1alpha,25(OH)(2)D(3), respectively. These metabolites appear to be closely related to the C-23 hydroxylation pathway, because human CYP24A1 produces much more of these metabolites than does rat CYP24A1. We propose that the C(24)-C(25) bond cleavage occurs by a unique reaction mechanism including radical rearrangement. Namely, after hydrogen abstraction of the C-23 position of 1alpha,25(OH)(2)D(3), part of the substrate-radical intermediate is converted into 25,26,27-trinor-23-ene-1alpha(OH)D(3), while a major part of them is converted into 1alpha,23,25(OH)(3)D(3). Because the C(24)-C(25) bond cleavage abolishes the binding affinity of 1alpha,25(OH)D(3) for the vitamin D receptor, this reaction is quite effective for inactivation of 1alpha,25(OH)D(3).
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/24,25-Dihydroxyvitamin D 3,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitriol,
http://linkedlifedata.com/resource/pubmed/chemical/Carbon,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcitriol,
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
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0006-2960
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
20
|
| pubmed:volume |
43
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
4530-7
|
| pubmed:dateRevised |
2008-8-16
|
| pubmed:meshHeading |
pubmed-meshheading:15078099-24,25-Dihydroxyvitamin D 3,
pubmed-meshheading:15078099-Animals,
pubmed-meshheading:15078099-Calcitriol,
pubmed-meshheading:15078099-Carbon,
pubmed-meshheading:15078099-Catalysis,
pubmed-meshheading:15078099-Cattle,
pubmed-meshheading:15078099-Chromatography, High Pressure Liquid,
pubmed-meshheading:15078099-Chromatography, Liquid,
pubmed-meshheading:15078099-Cytochrome P-450 Enzyme System,
pubmed-meshheading:15078099-Escherichia coli,
pubmed-meshheading:15078099-Humans,
pubmed-meshheading:15078099-Hydroxylation,
pubmed-meshheading:15078099-Mass Spectrometry,
pubmed-meshheading:15078099-Protein Binding,
pubmed-meshheading:15078099-Rats,
pubmed-meshheading:15078099-Receptors, Calcitriol,
pubmed-meshheading:15078099-Recombinant Proteins,
pubmed-meshheading:15078099-Steroid Hydroxylases,
pubmed-meshheading:15078099-Substrate Specificity
|
| pubmed:year |
2004
|
| pubmed:articleTitle |
Novel metabolism of 1 alpha,25-dihydroxyvitamin D3 with C24-C25 bond cleavage catalyzed by human CYP24A1.
|
| pubmed:affiliation |
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa, Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|