Source:http://linkedlifedata.com/resource/pubmed/id/19167490
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-2
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pubmed:dateCreated |
2009-3-31
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pubmed:abstractText |
Cytochrome P4507B1 7alpha-hydroxylates dehydroepiandrosterone (DHEA), epiandrosterone (EpiA) and 5alpha-androstane-3beta,17beta-diol (Adiol). 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) interconverts 7alpha- and 7beta-forms. Whether the interconversion proceeds through oxido-reductive steps or epimerase activity was investigated. Experiments using [(3)H]-labelled 7beta-hydroxy-DHEA, 7beta-hydroxy-EpiA and 7beta-hydroxy-Adiol showed the (3)H-label to accumulate in the 7-oxo-DHEA trap but not in 7-oxo-EpiA or 7-oxo-Adiol traps. Computed models of 7-oxygenated steroids docked in the active site of 11beta-HSD1 either in a flipped or turned form relative to cortisone and cortisol. 7-Oxo-steroid reduction in 7alpha- or 7beta-hydroxylated derivatives resulted from either turned or flipped forms. 11beta-HSD1 incubation in H(2)(18)O medium with each 7-hydroxysteroid did not incorporate (18)O in 7-hydroxylated derivatives of EpiA and Adiol independently of the cofactor used. Thus oxido-reductive steps apply for the interconversion of 7alpha- and 7beta-hydroxy-DHEA through 7-oxo-DHEA. Epimerization may proceed on the 7-hydroxylated derivatives of EpiA and Adiol through a mechanism involving the cofactor and Ser(170). The physiopathological importance of this epimerization process is related to 7beta-hydroxy-EpiA production and its effects in triggering the resolution of inflammation.
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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/11-beta-Hydroxysteroid...,
http://linkedlifedata.com/resource/pubmed/chemical/Androstane-3,17-diol,
http://linkedlifedata.com/resource/pubmed/chemical/Androsterone,
http://linkedlifedata.com/resource/pubmed/chemical/CYP7B1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Dehydroepiandrosterone,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Steroids
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1879-1220
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
114
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
57-63
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pubmed:meshHeading |
pubmed-meshheading:19167490-11-beta-Hydroxysteroid Dehydrogenase Type 1,
pubmed-meshheading:19167490-Androstane-3,17-diol,
pubmed-meshheading:19167490-Androsterone,
pubmed-meshheading:19167490-Catalytic Domain,
pubmed-meshheading:19167490-Dehydroepiandrosterone,
pubmed-meshheading:19167490-Humans,
pubmed-meshheading:19167490-Hydroxylation,
pubmed-meshheading:19167490-Molecular Structure,
pubmed-meshheading:19167490-Oxidation-Reduction,
pubmed-meshheading:19167490-Steroid Hydroxylases,
pubmed-meshheading:19167490-Steroids
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pubmed:year |
2009
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pubmed:articleTitle |
Epimerase activity of the human 11beta-hydroxysteroid dehydrogenase type 1 on 7-hydroxylated C19-steroids.
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pubmed:affiliation |
Chaire de Génie Biologique, EA-3199, Biotechnologie, Conservatoire National des Arts et Métiers, 2 rue Conté, 75003 Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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