3,11,20-trioxo-pregn-4-en-21-al | 95283-12-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3,11,20-trioxo-pregn-4-en-21-al
• 英文别名: 11,21-Dioxoprogesterone；2-[(8S,9S,10R,13S,14S,17S)-10,13-dimethyl-3,11-dioxo-2,6,7,8,9,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoacetaldehyde
• CAS: 95283-12-8
• 化学式: C₂₁H₂₆O₄
• 分子量: 342.435
• InChiKey: GWUQLPRDKICNSB-KJQYFISQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  68.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,11,20-trioxo-pregn-4-en-21-al 、 乙酸酐 在 吡啶 、 溶剂黄146 作用下， 生成 20-Acetoxy-pregn-4,17(20)-dien-3,11,21-trion
  参考文献：
  名称：

  Identification and Synthesis of 4,17-Pregnadien-20-ol-21-al-3,11-dione Acetate¹

  摘要：

  DOI：

  10.1021/ja01576a058
• 作为产物：
  描述：

  11-去氢皮质甾酮 在 copper diacetate 作用下， 生成 3,11,20-trioxo-pregn-4-en-21-al
  参考文献：
  名称：

  Identification and Synthesis of 4,17-Pregnadien-20-ol-21-al-3,11-dione Acetate¹

  摘要：

  DOI：

  10.1021/ja01576a058

文献信息

• Expanded substrate screenings of human and Drosophila type 10 17β-hydroxysteroid dehydrogenases (HSDs) reveal multiple specificities in bile acid and steroid hormone metabolism: characterization of multifunctional 3α/7α/7β/17β/20β/21-HSD
  作者：Naeem SHAFQAT、Hanns-Ulrich MARSCHALL、Charlotta FILLING、Erik NORDLING、Xiao-Qiu WU、Lars BJÖRK、Johan THYBERG、Eva MÅRTENSSON、Samina SALIM、Hans JÖRNVALL、Udo OPPERMANN

  DOI：10.1042/bj20030877

  日期：2003.11.15

  17β-Hydroxysteroid dehydrogenases (17β-HSDs) catalyse the conversion of 17β-OH (-hydroxy)/17-oxo groups of steroids, and are essential in mammalian hormone physiology. At present, eleven 17β-HSD isoforms have been defined in mammals, with different tissue-expression and substrate-conversion patterns. We analysed 17β-HSD type 10 (17β-HSD10) from humans and Drosophila, the latter known to be essential in development. In addition to the known hydroxyacyl-CoA dehydrogenase, and 3α-OH and 17β-OH activities with sex steroids, we here demonstrate novel activities of 17β-HSD10. Both species variants oxidize the 20β-OH and 21-OH groups in C21 steroids, and act as 7β-OH dehydrogenases of ursodeoxycholic or isoursodeoxycholic acid (also known as 7β-hydroxylithocholic acid or 7β-hydroxyisolithocholic acid respectively). Additionally, the human orthologue oxidizes the 7α-OH of chenodeoxycholic acid (5β-cholanic acid, 3α,7α-diol) and cholic acid (5β-cholanic acid). These novel substrate specificities are explained by homology models based on the orthologous rat crystal structure, showing a wide hydrophobic cleft, capable of accommodating steroids in different orientations. These properties suggest that the human enzyme is involved in glucocorticoid and gestagen catabolism, and participates in bile acid isomerization. Confocal microscopy and electron microscopy studies reveal that the human form is localized to mitochondria, whereas Drosophila 17β-HSD10 shows a cytosolic localization pattern, possibly due to an N-terminal sequence difference that in human 17β-HSD10 constitutes a mitochondrial targeting signal, extending into the Rossmann-fold motif.

  17β-羟类固醇脱氢酶（17β-HSDs）催化类固醇中 17β-OH （-羟基）/17-氧代基团的转化，是哺乳动物激素生理过程中必不可少的物质。目前，哺乳动物中已确定有 11 种 17β-HSD 同工酶，它们的组织表达和底物转换模式各不相同。我们分析了人类和果蝇的 17β-HSD 10 型（17β-HSD10），已知后者在发育过程中至关重要。除了已知的羟基乙酰-CoA 脱氢酶、3α-OH 和 17β-OH 与性类固醇的活性之外，我们在此还证明了 17β-HSD10 的新活性。这两种变体都能氧化 C21 类固醇中的 20β-OH 和 21-OH 基团，并作为熊去氧胆酸或异熊去氧胆酸（也分别称为 7β-hydroxylithocholic acid 或 7β-hydroxyisolithocholic acid）的 7β-OH 脱氢酶发挥作用。此外，人类同源物还能氧化去氧胆酸（5β-胆酸，3α，7α-二醇）和胆酸（5β-胆酸）的 7α-OH 。这些新的底物特异性可以用基于同源大鼠晶体结构的同源模型来解释，该结构显示了一个宽阔的疏水裂隙，能够容纳不同方向的类固醇。这些特性表明，人类酶参与了糖皮质激素和孕激素的分解代谢，并参与了胆汁酸异构化。共聚焦显微镜和电子显微镜研究显示，人类的 17β-HSD10 定位于线粒体，而果蝇的 17β-HSD10 则显示出细胞质定位模式，这可能是由于人类 17β-HSD10 的 N 端序列差异造成的。