scholarly journals The Crystal Structure of Guinea Pig 11β-Hydroxysteroid Dehydrogenase Type 1 Provides a Model for Enzyme-Lipid Bilayer Interactions

2004 ◽  
Vol 280 (5) ◽  
pp. 3789-3794 ◽  
Author(s):  
Derek Ogg ◽  
Björn Elleby ◽  
Carina Norström ◽  
Karin Stefansson ◽  
Lars Abrahmsén ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Guinea Pig ◽  
Lipid Bilayer ◽  
Hydroxysteroid Dehydrogenase

scholarly journals Comparative Enzymology of 11β-Hydroxysteroid Dehydrogenase Type 1 from Glucocorticoid Resistant (Guinea Pig)VersusSensitive (Human) Species

2002 ◽  
Vol 278 (3) ◽  
pp. 2030-2035 ◽  
Author(s):  
Naeem Shafqat ◽  
Björn Elleby ◽  
Stefan Svensson ◽  
Jawed Shafqat ◽  
Hans Jörnvall ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Hydroxysteroid Dehydrogenase ◽  
Human Species ◽  
Comparative Enzymology

scholarly journals Comparative enzymology of 11β-hydroxysteroid dehydrogenase type 1 from six species

2005 ◽  
Vol 35 (1) ◽  
pp. 89-101 ◽  
Author(s):  
Spyridon Arampatzis ◽  
Bert Kadereit ◽  
Daniela Schuster ◽  
Zoltan Balazs ◽  
Roberto A S Schweizer ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Animal Experiments ◽  
Three Dimensional ◽  
Catalytic Efficiency ◽  
Hydroxysteroid Dehydrogenase ◽  
Binding Pocket ◽  
Substrate Affinity ◽  
Drug Candidates ◽  
Species Specific

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), catalyzing the intracellular activation of cortisone to cortisol, is currently considered a promising target to treat patients with metabolic syndrome; hence, there is considerable interest in the development of selective inhibitors. For preclinical tests of such inhibitors, the characteristics of 11β-HSD1 from the commonly used species have to be known. Therefore, we determined differences in substrate affinity and inhibitor effects for 11β-HSD1 from six species. The differences in catalytic activities with cortisone and 11-dehydrocorticosterone were rather modest. Human, hamster and guinea-pig 11β-HSD1 displayed the highest catalytic efficiency in the oxoreduction of cortisone, while mouse and rat showed intermediate and dog the lowest activity. Murine 11β-HSD1 most efficiently reduced 11-dehydrocorticosterone, while the enzyme from dog showed lower activity than those from the other species. 7-Ketocholesterol (7KC) was stereospecifically converted to 7β-hydroxycholesterol by recombinant 11β-HSD1 from all species analyzed except hamster, which showed a slight preference for the formation of 7α-hydroxycholesterol. Importantly, guinea-pig and canine 11β-HSD1 displayed very low 7-oxoreductase activities. Furthermore, we demonstrate significant species-specific variability in the potency of various 11β-HSD1 inhibitors, including endogenous compounds, natural chemicals and pharmaceutical compounds. The results suggest significant differences in the three-dimensional organization of the hydrophobic substrate-binding pocket of 11β-HSD1, and they emphasize that species-specific variability must be considered in the interpretation of results obtained from different animal experiments. The assessment of such differences, by cell-based test systems, may help to choose the appropriate animal for safety and efficacy studies of novel potential drug candidates.

The role of hepatic 11[b]-hydroxysteroid dehydrogenase type 1 in cholesterol homeostasis

2013 ◽  
pp. 1-1
Author(s):  
Kajal Manwani ◽  
Tak Y Man ◽  
Christopher J Kenyon ◽  
Ruth Andrew ◽  
Karen E Chapman ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Cholesterol Homeostasis

Macrophage-specific 11b-hydroxysteroid dehydrogenase type 1 deficiency promotes angiogenesis but impairs resolution of K/BxN serum induced arthritis

2013 ◽  
pp. 1-1
Author(s):  
Zhenguang Zhang ◽  
Agnes Coutinho ◽  
Patrick Hadoke ◽  
Donald Salter ◽  
Jonathan Seckl ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase

Suppression of 11[beta]-hydroxysteroid dehydrogenase type 1 target gene regulation by hypoxia

2016 ◽  
Author(s):  
Bushra Shammout ◽  
Adewonuola Alase ◽  
Miriam Wittmann ◽  
Paul Stewart ◽  
Ana Tiganescu
Keyword(s):  
Gene Regulation ◽  
Target Gene ◽  
Hydroxysteroid Dehydrogenase
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