Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2009-3-31
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1879-1220
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
57-63
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Epimerase activity of the human 11beta-hydroxysteroid dehydrogenase type 1 on 7-hydroxylated C19-steroids.
pubmed:affiliation
Chaire de Génie Biologique, EA-3199, Biotechnologie, Conservatoire National des Arts et Métiers, 2 rue Conté, 75003 Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't