基因组组织人类5 beta-reductase和假基因和酶的底物选择性表达。
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夏博诺,六世
基因组组织人类5 beta-reductase和假基因和酶的底物选择性表达。
Biochim Biophys学报。2001年1月26日,1517 (2):228 - 35。
- PubMed ID
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11342103 (在PubMed]
- 文摘
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5 beta-reductase酶催化的还原4-ene 3-ketosteroids,转换成5 beta-dihydro-3-ketosteroids,因此,可以参与4-cholestene-3-one的新陈代谢,黄体酮,17 -羟孕酮,醛固酮,肾上腺酮、皮质醇,4-androstenedione,睾酮。在这项研究中,我们报告的基因组结构人类5 beta-reductase基因,其组织分布特征的intronless假基因和酶的底物选择性。活跃的基因编码5 beta-reductase包含9个外显子最喜欢aldo-keto还原酶家族的成员,但是覆盖的基因序列,超过42 kb,远远超过这个家庭的其他成员的顺序。有许多大的内含子,特别是内含子3、4和7,跨度约。7 kb,内含1包含超过10 kb。北部污点分析显示三个带大小为1.3,2.2和2.7 kb。1.3和2.7 kb带肝中高度表达,而较弱的2.2和1.3 kb乐队曾被观察到在睾丸和结肠,分别。我们还发现了一个intronless基因有86%与5 beta-reductase cDNA序列同源性。序列包含了许多以来停止密码子,这个基因最有可能是一个假基因。更精确地确定酶的底物选择性,我们建立了一个稳定的细胞系表达人类5 beta-reductase改变胚胎肾细胞(hek - 293)。 The transfected cells efficiently catalyze the transformation of progesterone, androstenedione, 17alpha-hydroxyprogesterone and testosterone. However, they catalyze much less efficiently the transformation of compounds containing an 11beta-hydroxy group, such as aldosterone, corticosterone and cortisol. In addition to its role in cholesterol catabolism, it is well recognized that 5beta-reductase inactivates active androgens. Indeed, 5beta-dihydrotestosterone (5beta-DHT), the product of the reduction of testosterone by 5beta-reductase, is not active while its 5~-isomer (DHT) is the most potent natural androgen. Recent findings show that 5beta-pregnanes are active ligands in the induction of CYP3A through the orphan receptor hPAR. Our results thus open an opportunity for studying the new role of 5beta-reductase in the formation of a new type of active steroids.