title: 11β-Hydroxysteroid dehydrogenase 1: Regeneration of active glucocorticoids is only part of the story.
abstract: 11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) is an endoplasmic reticulum membrane enzyme with its catalytic site facing the luminal space. It functions primarily as a reductase, driven by the supply of its cosubstrate NADPH by hexose-6-phosphate dehydrogenase (H6PDH). Extensive research has been performed on the role of 11β-HSD1 in the regeneration of active glucocorticoids and its role in inflammation and metabolic disease. Besides its important role in the fine-tuning of glucocorticoid action, 11β-HSD1 is a multi-functional carbonyl reductase converting several 11- and 7-oxosterols into the respective 7-hydroxylated forms. Moreover, 11β-HSD1 has a role in phase I biotransformation reactions and catalyzes the carbonyl reduction of several non-steroidal xenobiotics. Recent observations from experiments using selective inhibitors and studies with transgenic mice indicated a role for 11β-HSD1 in oxysterol metabolism and in bile acid homeostasis, with evidence for glucocorticoid-independent effects on gene expression. This review focuses on the promiscuity of 11β-HSD1 to accept structurally distinct substrates and discusses recent progress mainly on non-glucocorticoid substrates. This article is part of a Special Issue entitled 'Enzyme Promiscuity and Diversity'.
authors.affiliation: Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address: alex.odermatt@unibas.ch.
authors.forename: Alex
authors.initials: A
authors.lastname: Odermatt
authors.affiliation: Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Klusonova
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007653:Ketocholesterols / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D005938:Glucocorticoids; D007653:Ketocholesterols; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C003001:7-ketocholesterol
keywords: 11β-Hydroxysteroid dehydrogenase; Bile acid; Carbonyl reduction; Cholesterol; Glucocorticoid; Metabolism; Xenobiotic