The R337C mutation generates a high Km 11{beta}-hydroxysteroid dehydrogenase type II enzyme in a family with apparent mineralocorticoid excess
- Baker Medical Research Institute, Melbourne (Australia); and others
The 11{beta}-hydroxysteroid dehydrogenase type II enzyme (11{beta}HSD2) inactivates glucocorticoids in the kidney and thus permits aldosterone to occupy the non-selective mineralocortiocid 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 11{beta}HSD2 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. 10 refs., 2 figs.
- OSTI ID:
- 443622
- Journal Information:
- Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 10 Vol. 80; ISSN JCEMAZ; ISSN 0021-972X
- Country of Publication:
- United States
- Language:
- English
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