3-Oxo-5beta-cholanate

• 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-Oxo-5beta-cholanate
• 英文别名: (4R)-4-[(5R,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3-oxo-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pentanoate
• 化学式: C24H37O3-
• 分子量: 373.5
• InChiKey: KIQFUORWRVZTHT-OPTMKGCMSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Oxo-5beta-cholanate 、 氢(+1)阳离子 、 NADH 生成 Isolithocholate 、 nicotinamide adenine dinucleotide
  参考文献：
  名称：

  A biosynthetic pathway for a prominent class of microbiota-derived bile acids

  摘要：

  通过生物信息学和系统发生学搜索，确定了在细菌胆汁酸生物合成途径中参与将二氯苯甲醚（DCA）转化为异二氯苯甲醚（isoDCA）的五种酶。对胆汁酸生物学作用的研究确定了生产者 R. gnavus 和非生产者 Bacteroides 之间的互作关系。 肠道胆汁酸池的浓度为毫摩尔，个体之间的组成差异很大，并且与代谢疾病和癌症有关。虽然这些分子几乎全部来自微生物群，但人们对负责其生物合成的细菌种类和基因知之甚少。在这里，我们报告了肠道中含量第二高的3δ²-羟基（异）-胆酸的生物合成途径，在一些人体内，3δ²-羟基（异）-胆酸的含量超过300 ¼M，而在另一些人体内则没有。我们首次发现gnavus反刍球菌能产生异胆酸，它是一种比以前已知的生产者更丰富的共生菌，异胆酸途径能解毒脱氧胆酸，从而有利于关键菌属Bacteroides的生长。通过揭示一类丰富胆汁酸的生物合成基因，我们的工作为预测和合理改变胆汁酸库的组成奠定了基础。

  DOI：

  10.1038/nchembio.1864
• 作为产物：
  描述：

  (4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate 、 NADP⁺ 生成 3-Oxo-5beta-cholanate 、 氢(+1)阳离子 、 NADPH(4-)
  参考文献：
  名称：

  A biosynthetic pathway for a prominent class of microbiota-derived bile acids

  摘要：

  通过生物信息学和系统发生学搜索，确定了在细菌胆汁酸生物合成途径中参与将二氯苯甲醚（DCA）转化为异二氯苯甲醚（isoDCA）的五种酶。对胆汁酸生物学作用的研究确定了生产者 R. gnavus 和非生产者 Bacteroides 之间的互作关系。 肠道胆汁酸池的浓度为毫摩尔，个体之间的组成差异很大，并且与代谢疾病和癌症有关。虽然这些分子几乎全部来自微生物群，但人们对负责其生物合成的细菌种类和基因知之甚少。在这里，我们报告了肠道中含量第二高的3δ²-羟基（异）-胆酸的生物合成途径，在一些人体内，3δ²-羟基（异）-胆酸的含量超过300 ¼M，而在另一些人体内则没有。我们首次发现gnavus反刍球菌能产生异胆酸，它是一种比以前已知的生产者更丰富的共生菌，异胆酸途径能解毒脱氧胆酸，从而有利于关键菌属Bacteroides的生长。通过揭示一类丰富胆汁酸的生物合成基因，我们的工作为预测和合理改变胆汁酸库的组成奠定了基础。

  DOI：

  10.1038/nchembio.1864

文献信息

• Characterization of NAD-dependent 3α- and 3β-hydroxysteroid dehydrogenase and of NADP-dependent 7β-hydroxysteroid dehydrogenase from Peptostreptococcus productus
  作者：Rudolf Edenharder、Andreas Pfützner、Rainer Hammann

  DOI：10.1016/0005-2760(89)90272-5

  日期：1989.8

  physiological and biochemical data as a strain of Peptostreptococcus roductus, was shown to contain NAD-dependent 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and a NADP-dependent 7 beta-hydroxysteroid dehydrogenase. All enzyme activities could be demonstrated in crude extracts and in membrane fractions. The 3 alpha- and 3 beta-hydroxysteroid dehydrogenases were synthesized constitutively. Specific enzymatic

  人类粪便分离物的特征在于形态学，生理学和生化数据，如Peptostreptococcus roductus菌株，显示含有NAD依赖性的3α-和3β-羟基类固醇脱氢酶和NADP依赖性的7β-羟基类固醇脱氢酶。所有酶活性都可以在粗提物和膜级分中证明。本构地合成了3个α-和3个β-羟基类固醇脱氢酶。当细菌在3-酮胆汁酸存在下生长时，特定的酶活性显着降低，而其他胆汁酸则无效。对于3α（3β）-羟基类固醇脱氢酶，估计最适pH为8.5（9.5）和分子量为95,000（132,000）。3个α-和3个β-羟基类固醇脱氢酶对热敏感（在50摄氏度下约75％的失活10分钟）。7β-羟类固醇脱氢酶已经存在于未诱导的细胞中，但是当细菌在7-酮胆汁酸存在下生长时，比活性可以提高至2.5倍以上。二取代胆汁酸比三取代胆汁酸更有效，熊去氧胆酸作为诱导剂无效。7β-羟基类固醇脱氢酶的最适pH为10.0，分子量约为82,00
• Partial purification and characterization of an NAD-dependent 3 beta-hydroxysteroid dehydrogenase from Clostridium innocuum
  作者：R Edenharder、M Pfützner

  DOI：10.1128/aem.55.6.1656-1659.1989

  日期：1989.6

  In nine strains of Clostridium innocuum, 3 beta-hydroxysteroid-dehydrogenating activities were detected. 3 beta, 7 alpha, 12 alpha-Trihydroxy- and 3 beta-hydroxy-12-keto-5 beta-cholanoic acids were identified as reduction products of the respective 3-keto bile acids by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry. One strain was shown to contain a NAD-dependent 3 beta-hydroxysteroid dehydrogenase. Enzyme production was constitutive in the absence of added bile acids. The specific enzyme activity was significantly reduced by growth medium supplementation with 3-keto bile acids, with trisubstituted acids being more effective than disubstituted ones. A pH optimum of 10.0 to 10.2 was found after partial purification by DEAE-cellulose chromatography. A molecular weight of about 56,000 was established. 3 beta-hydroxysteroid dehydrogenase activity was also found in the membrane fraction after solubilization with Triton X-100, suggesting that the enzyme was originally membrane bound. The enzyme reduced a 3-keto group in unconjugated and conjugated bile acids, lower Km values being demonstrated with disubstituted than with trisubstituted bile acids. Keto functions at C-7 and C-12 further reduced the Km value. The enzyme was found to be partially heat labile (86% inactivation at 50 degrees C for 10 min).

  在九株无芽孢梭菌中检测到了三种3-β-羟基甾体脱氢酶活性。通过气相液相色谱和气相液相色谱-质谱联用技术，确定了3-酮胆汁酸的还原产物为3β,7α,12α-三羟基-和3β-羟基-12-酮-5β-胆酸。其中一株菌株含有一种依赖NAD的3-β-羟基甾体脱氢酶。在未添加胆汁酸的情况下，酶的产生是固有的。生长基质添加3-酮胆汁酸会显著降低特定酶活性，三取代酸比二取代酸更有效。通过DEAE-纤维素色谱部分纯化后，发现最适pH为10.0至10.2，约有56000的分子量。在Triton X-100溶解后，膜部分也发现了3-β-羟基甾体脱氢酶活性，表明该酶最初是与膜结合的。该酶能还原未结合和结合的胆汁酸中的3-酮基团，二取代胆汁酸的Km值低于三取代胆汁酸。C-7和C-12的酮基团进一步降低了Km值。该酶部分热敏感（在50摄氏度下加热10分钟，失活率为86%）。
• 3β-Hydroxysterod Dehydrogenase of Ruminococcus sp. from Human Intestinal Bacteria
  作者：Taiko AKAO、Teruaki AKAO、MASAO HATTORI、Tsuneo NAMBA、Kyoichi KOBASHI

  DOI：10.1093/oxfordjournals.jbchem.a135612

  日期：1986.4

  Ruminococcus sp. PO1-3 obtained from human intestinal flora is able to reduce dehydrocholate as well as 3-ketoglycyrrhetinate. From this bacterium dehydrocholate- and 3-ketoglycyrrhetinate-reducing activities were purified one thousand fold together with 3-ketocholanate-reducing and 3β-hydroxyglycyrrhetinate (glycyrrhetic acid) oxidizing activities by means of Mātrex Red A, Sephadex G-200 and Octyl-Sepharose column chromatography. The purified enzyme catalyzed the reduction of dehydrocholic acid to β-hydroxy-7,12-diketocholanic acid and of 3-ketocholanic acid to 3β-hydroxycholanic acid. Studies on substrate specificity revealed that the enzyme had absolute specificity for the β-configuration of a hydroxyl group at the 3 position of bile acid and steroids having no double bond in the A/B ring. This enzyme was neither β-hydroxysteroid dehydrogenase [EC 1.1.1.51] nor 3β-hydroxy-Δ5-steroid dehydrogenase [EC 1.1.1.145], but a novel type of enzyme, defined as 3β-hydroxysteroid dehydrogenase.

  从人体肠道菌群中分离出的反刍球菌属（Ruminococcus sp.）PO1-3能够还原脱氢胆酸和3-酮甘草亭酸。通过Mātrex Red A、Sephadex G-200和Octyl-Sepharose柱层析法，从这种细菌中分离出还原脱氢胆酸和3-酮甘草亭酸的活性，以及还原3-酮胆酸和氧化3β-羟基甘草亭酸（甘草酸）的活性，纯化倍数高达1000倍。纯化的酶催化脱氢胆酸还原为β-羟基-7,12-二酮胆酸，3-酮胆酸还原为3β-羟基胆酸。对底物特异性的研究表明，该酶对胆酸和类固醇中A/B环无双键的3位羟基的β构型具有绝对特异性。这种酶既不是β-羟基类固醇脱氢酶[EC 1.1.1.51]，也不是3β-羟基-Δ5-类固醇脱氢酶[EC 1.1.1.145]，而是一种新型酶，被定义为3β-羟基类固醇脱氢酶。