The 11β-hydroxysteroid dehydrogenase type II enzyme: Biochemical consequences of the congenital R337C mutation

Paolo Ferrari, Varuni R. Obeyesekere, Kevin Li, Robert K. Andrews, Zygmunt S. Krozowski

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)


The 11β-hydroxysteroid dehydrogenase type II enzyme (11βHSD2) convert cortisol to cortisone, allowing the non-selective mineralocorticoid receptor to bind aldosterone. When the activity of this enzyme is compromised, as occurs in licorice intoxication or in the congenital syndrome of apparent mineralocorticoid excess (AME), there is marked sodium retention, hypokalemia, and hypertension. The first proof that this enzyme was defective in AME came from the identification of the R337C mutation in a number of siblings with the syndrome. Subsequent expression studies showed that the mutant had a K(m) one order of magnitude higher than the wild-type enzyme while in the cell-free system it was without detectable activity. In the present work we have extended our studies on this mutant and provide evidence that the mutant protein may also partially inhibit the wild-type enzyme in heterozygotes. Furthermore, experiments incorporating the protein synthesis inhibitor cycloheximide show that the mutant enzyme is less stable than the wild-type activity in intact cells. These results suggest that mutations in the 11βHSD2 enzyme may have multiple consequences for the mineralocorticoid target cell.

Original languageEnglish
Pages (from-to)197-200
Number of pages4
Issue number4
Publication statusPublished - 1 Jan 1996
Externally publishedYes


  • 11β-hydroxysteroid dehydrogenase
  • glucocorticoid
  • mineralocorticoid
  • mutation

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