地塞米松在人类肾脏代谢:烟酰胺腺嘌呤dinucleotide-dependent 11 beta-reduction。
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汉克Diederich年代,B, Oelkers W,巴尔V
地塞米松在人类肾脏代谢:烟酰胺腺嘌呤dinucleotide-dependent 11 beta-reduction。
82年5月,中国性金属底座。1997 (5):1598 - 602。
- PubMed ID
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9141556 (在PubMed]
- 文摘
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最近,两个截然不同的同功酶11 beta-hydroxysteroid-dehydrogenase (11 beta-hsd)已被克隆和几个物种的特征:同工酶11 beta-hsd-i广泛分布,双向的,喜欢是nad (H)和低底物亲和力。同工酶11 beta-hsd-ii似乎完全氧化生理糖皮质激素,使用NAD作为辅被用物,底物亲和力高,只存在于盐皮质激素和胎盘组织目标。合成类固醇氟在位置9中,然而,人类肾脏皮质片正在迅速减少。我们试图找出同工酶负责这个意想不到的还原酶活性。我们研究了11个beta-hsd活动对皮质醇(F) /可的松(E)和地塞米松(D) / 11-dehydro-dexamethasone (DH-D)微粒体准备从人类肾皮质。反应的E, F(不是DH-D D !), glucose-6-phosphate和遗传性葡萄糖- 6 -磷酸脱氢作为NADH / NADPH-regenerating添加系统。氧化的F E: NAD是专门使用辅被用物;亲和力(迈克尔的常数(公里)F = 25.5 nmol / L)和最大速度(Vmax = 22.9 nmol /毫克/分钟)高。减少E F:没有NADH / NADPH-regenerating系统,这个反应非常慢。有了这个系统,E的Km值在摩尔范围(80.6 nmol / L)和Vmax值很低(0.88 nmol /毫克/分钟)。 The reaction was clearly NADH-preferring. For the steroid pair F/E, the quotient Vmax(oxidation)/Vmax(reduction) (=26) demonstrates an equilibrium far on the 11-keto side. Oxidation of D to DH-D: With NAD as the only used cosubstrate, the kinetic analysis is compatible with the existence of two different NAD-dependent isoenzymes: Km for D = 327 nmol/L, Vmax = 53.5 nmol/mg/min and Km for D = 81.2 nmol/L; Vmax = 20.4 nmol/mg/min. Reduction of DH-D to D: The maximum velocity was higher than that of all other reactions tested: Vmax = 226.0 nmol/mg/min. The reaction was exclusively NADH-dependent; the Km value for DH-D was 68.4 nmol/L. For D/DH-D, the ratio Vmax(oxidation)/Vmax(reduction) was 0.24, demonstrating a shift to reductase activity with the reaction equilibrium far on the 11-hydroxy side. The reaction F to E was inhibited by E, DH-D, and D in a concentration-dependent manner. In conclusion, the cosubstrate dependence, the Km value of the oxidation of F and the product inhibition are in good correspondence with data for the cloned human 11beta-HSD-II. The NADH-dependent 11beta-reduction of E and especially of DH-D are inconsistent with the dogma of an unidirectional 11beta-HSD-II. The preference of D for the reductase reaction in human kidney slices is probably caused by the fluor atom in position 9, is catalyzed by 11beta-HSD-II, and leads to an activation of 11-DH-D to D in the human kidney.
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药物 目标 类 生物 药理作用 行动 NADH 皮质类固醇11-beta-dehydrogenase同工酶1 蛋白质 人类 未知的不可用 细节 - 药物酶
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药物 酶 类 生物 药理作用 行动 地塞米松 皮质类固醇11-beta-dehydrogenase同工酶1 蛋白质 人类 未知的底物细节 地塞米松 皮质类固醇11-beta-dehydrogenase同工酶2 蛋白质 人类 未知的底物细节 醋酸地塞米松 皮质类固醇11-beta-dehydrogenase同工酶1 蛋白质 人类 未知的底物细节 醋酸地塞米松 皮质类固醇11-beta-dehydrogenase同工酶2 蛋白质 人类 未知的底物细节 - 药物反应
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反应 细节
