Hexose-6-phosphate dehydrogenase determines the reaction direction of 11β-hydroxysteroid dehydrogenase type 1 as an oxoreductase

被引:192
作者
Atanasov, AG [1 ]
Nashev, LG [1 ]
Schweizer, RAS [1 ]
Frick, C [1 ]
Odermatt, A [1 ]
机构
[1] Univ Bern, Dept Clin Res, Div Nephrol & Hypertens, CH-3010 Bern, Switzerland
来源
FEBS LETTERS | 2004年 / 571卷 / 1-3期
关键词
11 beta-hydroxysteroid dehydrogenase; hexose-6-phosphate dehydrogenase; glucocorticoid; cortisol;
D O I
10.1016/j.febslet.2004.06.065
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The impact of hexose-6-phosphate dehydrogenase (H6PDH) on 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 activity was investigated upon coexpression in HEK-293 cells. Confocal microscopy analysis indicated colocalisation of both enzymes at the lumenal side of the endoplasmic reticulum (ER) membrane. Functional analysis in intact cells revealed fivefold stimulation of 11beta-HSD1 oxoreductase activity and sixfold decrease of dehydrogenase activity upon coexpression with H6PDH, without changing kinetic parameters in cell lysates. Thus, H6PDH directly determines the reaction direction of 11beta-HSD1 in intact cells as an oxoreductase without changing intrinsic catalytic properties of 11beta-HSD1 by regenerating NADPH in the ER-lumen. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:129 / 133
页数:5
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