The R337C mutation generates a high km 11β-hydroxysteroid dehydrogenase type II enzyme in a family with apparent mineralocorticoid excess

V. R. Obeyesekere, P. Ferrari, R. K. Andrews, R. C. Wilson, M. I. New, J. W. Funder, Z. S. Krozowski

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Abstract

The 11β-hydroxysteroid dehydrogenase type II enzyme (11βHSD2) inactivates glucocorticoids in the kidney and thus permits aldosterone to occupy the non-selective mineralocorticoid receptor in epithelial tissues. We have recently described a C to T transition in the HSD11B2 gene which results in an arginine to cysteine mutation (R337C) in the 11βHSD2 enzyme in a consanguineous family with three siblings suffering from Apparent Mineralocorticoid Excess (AME). In the present study we have examined the metabolism of cortisol in mammalian cells transfected with plasmids expressing the wild type and mutant enzymes. In whole cells the Km of the normal enzyme was 110nM, while the enzyme containing the R337C mutation displayed a Km of 1010nM. Further experiments revealed that the mutant was totally inactive in cell free preparations, suggesting that it has additional properties which may compromise its activity in whole cells.

Original languageEnglish
Pages (from-to)3381-3383
Number of pages3
JournalJournal of Clinical Endocrinology and Metabolism
Volume80
Issue number11
DOIs
StatePublished - Nov 1995
Externally publishedYes

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