Source:http://linkedlifedata.com/resource/pubmed/id/10362535
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1999-6-28
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pubmed:abstractText |
Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1) plays a crucial role in the last step of the synthesis of estrogens. A detailed kinetic study demonstrated that the enzyme shows about 240 fold higher specificity towards estrone reduction than estradiol oxidation at physiological pH using tri-phosphate cofactors. The kcat/Km values are 96 +/- 10 and 0.4 +/- 0.1 s-1 (microM)-1 respectively for the above two reactions. However, it has been shown that this difference is closely linked to the use of NADPH and NADP cofactors. A binding study using equilibrium dialysis indicated similar KD (equilibrium dissociation constant) of 11 +/- 1 and 4.7 +/- 0.9 microM for estrone and estradiol, respectively. The binding affinity of 17beta-HSD1 to estrone was significantly increased with a KD of 1.6 +/- 0.2 microM in the presence of NADP, the latter used as an analogue of the NADPH. The results of binding studies agree with the steady-state kinetics, which showed that the Km of estrone is 12-fold lower when using NADPH as a cofactor than when using NADH. These results strongly suggest that the cofactor plays a crucial role in the stimulation of the specificity for estrogen reduction.
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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/17-Hydroxysteroid Dehydrogenases,
http://linkedlifedata.com/resource/pubmed/chemical/3 (or 17)-beta-hydroxysteroid...,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Estrone,
http://linkedlifedata.com/resource/pubmed/chemical/NAD,
http://linkedlifedata.com/resource/pubmed/chemical/NADP
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 1999 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
259
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
489-93
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10362535-17-Hydroxysteroid Dehydrogenases,
pubmed-meshheading:10362535-Binding Sites,
pubmed-meshheading:10362535-Enzyme Induction,
pubmed-meshheading:10362535-Estradiol,
pubmed-meshheading:10362535-Estrone,
pubmed-meshheading:10362535-Humans,
pubmed-meshheading:10362535-Hydrogen-Ion Concentration,
pubmed-meshheading:10362535-Kinetics,
pubmed-meshheading:10362535-NAD,
pubmed-meshheading:10362535-NADP,
pubmed-meshheading:10362535-Oxidation-Reduction,
pubmed-meshheading:10362535-Placenta,
pubmed-meshheading:10362535-Protein Binding
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pubmed:year |
1999
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pubmed:articleTitle |
Human estrogenic 17beta-hydroxysteroid dehydrogenase: predominance of estrone reduction and its induction by NADPH.
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pubmed:affiliation |
CHUL Research Center, Laval University, Quebec, Quebec, G1V 4G2, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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