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

  • FEBS Lett. 2004 Jul 30;571(1-3):129-33. doi: 10.1016/j.febslet.2004.06.065.
Atanas G Atanasov  1 ,  Lyubomir G Nashev ,  Roberto A S Schweizer ,  Christoph Frick ,  Alex Odermatt
Affiliations
  • 1. Division of Nephrology and Hypertension, Department of Clinical Research, University of Berne, Freiburgstrasse 15, 3010 Berne, Switzerland.
PMID: 15280030 DOI: 10.1016/j.febslet.2004.06.065
Abstract

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.