Kinetic studies on rabbit liver glucocorticoid 5α-reductase

被引:3
作者
Kuhlmann, K [1 ]
Bühler, H [1 ]
Ragosch, V [1 ]
Halis, G [1 ]
Weitzel, HK [1 ]
Hundertmark, S [1 ]
机构
[1] Free Univ Berlin, Klinikum Benjamin Franklin, Frauenklin & Poliklin, Dept Obstet & Gynecol, D-12200 Berlin, Germany
关键词
5-alpha-reductase; glucocorticosteroids; EC; 1.3.99.5; liver; rabbit;
D O I
10.1055/s-2007-978580
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The serum concentration of active glucocorticosteroids depends not only on adrenal synthesis but also on enzymatic activation of 11-dehydro-glucocorticoids in the liver by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). In order to define the respective involvement of other regulative enzymes in the metabolism of 11-dehydro-glucocorticoids in the river, the objective of this study was to evaluate the kinetic behavior of NADPH:delta 4-3-ketosteroid-5alpha-reductase (5 alpha-reductase, EC 1.3.99.5). The interrelations to liver 11 beta-HSD1 will be discussed. The kinetic properties of 5 alpha-reductase of the rabbit liver were measured by a radioenzymatic assay and characterized with respect to protein-, substrate-, cosubstrate-, and pH-dependence. Michaelis-Menten enzyme kinetic parameters (Km and Vmax) were obtained for the formation of 5 alpha-reduced 11-dehydrocorticosterone and corticosterone metabolites. We found that both 11-dehydrocorticosterone (Km 4.2 x 10(-6) mol/l, Vmax 2600 pmol x min(-1) x mg(-1)) and corticosterone (Km 0.5 x 10(-6) mol/l, Vmax 38 pmol x min(-1) x mg(-1)) exhibit a high affinity to 5 alpha-reductase. With respect to cosubstrate-, pH-dependence and finasteride inhibition, it is likely that 5 alpha-dehydrocorticosterone metabolism is primarily controlled by isoenzyme 5 alpha-reductase type 1. This study shows that the deactivation of GCS especially of 11-dehydro-glucocorticoids via 5 alpha-reductase is an important metabolic pathway in the liver. The metabolic activation of GCS by 11 beta-HSD could possibly lead to an excess of GCS in the hepatocytes. Due to 5 alpha-reductase activity this excess can be limited - on the level of CORT as well as of 11-DHC.
引用
收藏
页码:20 / 25
页数:6
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