Linked Life Data

11856542

Source:http://linkedlifedata.com/resource/pubmed/id/11856542

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3-4
pubmed:dateCreated
2002-2-21
pubmed:abstractText
Aromatase catalyzes the conversion of androgens to estrogens through three sequential oxygenations. To gain insight into the catalytic function of aromatase and its aromatization mechanism, we studied the inhibition of human placental aromatase by 4 beta,5 beta-epoxyandrostenedione (5) as well as its 19-hydroxy and 19-oxo derivatives (6 and 7, respectively), and we also examined the biochemical aromatization of these steroids. All of the epoxides were weak competitive inhibitors of aromatase with apparent K(i) values ranging from 5.0 microM to 30 microM. The 19-methyl and 19-oxo compounds 5 and 7 inactivated aromatase in a time-dependent manner with k(inact) of 0.048 and 0.110 min(-1), respectively, in the presence of NADPH. In the absence of NADPH, only the former inhibited aromatase with a k(inact) of 0.091 min(-1). However, 19-hydroxy steroid 6 did not cause irreversible inactivation either in the presence or absence of NADPH. Gas chromatography-mass spectrometric analysis of the metabolite produced by a 5-min incubation of the three epoxides with human placental microsomes in the presence of NADPH under air revealed that all three compounds were aromatized to produce estradiol with rates of 8.82, 0.51, and 1.62 pmol/min/mg protein for 5, 6, and 7, respectively. In each case, the aromatization was efficiently prevented by 19-hydroxyandrost-4-en-17-one, a potent aromatase inhibitor. On the basis of the aromatization and inactivation results, it seems likely that the two pathways, aromatization and inactivation, may proceed, in part, through a common intermediate, 19-oxo compound 7, although they may be principally different.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0039-128X
pubmed:author
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
185-93
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Time-dependent aromatase inactivation by 4 beta,5 beta-epoxides of the natural substrate androstenedione and its 19-oxygenated analogs.
pubmed:affiliation
Tohoku Pharmaceutical University, 4-1 Komatsushima-4-chome, Aobaku, Sendai 981-8558, Japan. numazawa@tohoku-pharm.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't