Hexose-6-phosphate dehydrogenase determines the reaction direction of 11beta-hydroxysteroid dehydrogenase type 1 as an oxoreductase.
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.
Division of Nephrology and Hypertension, Department of Clinical Research, University of Berne, Freiburgstrasse 15, 3010 Berne, Switzerland.
Atanas G
AG
Atanasov
Lyubomir G
LG
Nashev
Roberto A S
RA
Schweizer
Christoph
C
Frick
Alex
A
Odermatt
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D020121:5' Untranslated Regions / Q000235:genetics; D017667:Adipocytes / Q000201:enzymology; D001483:Base Sequence; D002237:Carbohydrate Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D003348:Cortisone / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007668:Kidney; D007700:Kinetics; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism
D020121:5' Untranslated Regions; D012333:RNA, Messenger; D011994:Recombinant Proteins; D010088:Oxidoreductases; D002237:Carbohydrate Dehydrogenases; C020552:galactose-6-phosphate dehydrogenase; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone