Taurochenodeoxycholate anion

• 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: Taurochenodeoxycholate anion
• 英文别名: 2-[[(4R)-4-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonate
• 化学式: C26H44NO6S-
• 分子量: 498.7
• InChiKey: BHTRKEVKTKCXOH-BJLOMENOSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  水 、 Taurochenodeoxycholate anion 生成 Chenodeoxycholate anion 、 牛磺酸
  参考文献：
  名称：

  长双歧杆菌胆汁盐水解酶的生化和遗传学表征。

  摘要：

  从长双歧杆菌SBT2928分离出胆汁盐水解酶（BSH），纯化并鉴定。此外，我们首次描述了双歧杆菌属成员中编码BSH（bsh）的基因的克隆和分析。根据推导的氨基酸序列测定，该酶的天然分子量为125,000-130,000，亚单位分子量为35,024，表明该酶是四聚体。长双歧杆菌BSH的最适pH为5至7，最适温度为40℃。该酶被硫醇酶抑制剂强烈抑制，表明Cys残基可能参与催化反应。长双歧杆菌的BSH可以水解所有六种主要的人胆汁盐和至少两种动物胆汁盐。基于特异性和K（m）值，检测到对甘氨酸缀合的胆汁酸略有偏爱。确定了bsh的核苷酸序列，并将其用于同源性研究，转录本分析以及各种突变体的构建和分析。与其他细菌的BSH和球形芽孢杆菌的青霉素V酰基转移酶（PVA）的同源性很高。基于已经阐明晶体结构的BSH和PVA的相似性，可以将BSH分类为N末端亲核水解酶，而将Cys作为N末端氨基酸。通过定点诱变进行的

  DOI：

  10.1128/aem.66.6.2502-2512.2000
• 作为产物：
  描述：

  chenodeoxycholoyl-CoA(4-) 、 牛磺酸 生成 coenzyme A 、 氢(+1)阳离子 、 Taurochenodeoxycholate anion
  参考文献：
  名称：

  人胆汁酸-CoA：氨基酸N-酰基转移酶在脂肪酸与甘氨酸的缀合中起作用。

  摘要：

  胆汁酸-CoA：氨基酸N-酰基转移酶（BACAT）催化胆汁酸与甘氨酸和牛磺酸的结合，从而排泄到胆汁中。通过使用定点诱变和序列比较，我们已鉴定出Cys-235，Asp-328和His-362构成人BACAT（hBACAT）中的催化三联体，并将BACAT鉴定为I型酰基辅酶A硫酯酶基因家族。因此，我们假设hBACAT也可能将脂肪酰基辅酶A和/或共轭脂肪酸水解为甘氨酸。我们在这里显示重组hBACAT也可以水解长链和非常长链的饱和酰基CoAs（主要是C16：0-C26：0），并且通过质谱法验证了hBACAT还可以将脂肪酸缀合到甘氨酸上。组织表达研究表明，BACAT在肝，胆囊以及近端和远端肠中都有强表达。然而，BACAT还可以在与胆汁酸形成和运输无关的多种组织中表达，这表明在调节长链脂肪酸的细胞内水平方面也起着重要的作用。在人皮肤成纤维细胞中的绿色荧光蛋白定位实验表明，hBACAT酶主要是胞质的。因此

  DOI：

  10.1074/jbc.m300987200

文献信息

• Cloning and sequencing of the 7 alpha-hydroxysteroid dehydrogenase gene from Escherichia coli HB101 and characterization of the expressed enzyme
  作者：T Yoshimoto、H Higashi、A Kanatani、X S Lin、H Nagai、H Oyama、K Kurazono、D Tsuru

  DOI：10.1128/jb.173.7.2173-2179.1991

  日期：1991.4

  The 7 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.159) gene from Escherichia coli HB101 was cloned and expressed in E. coli DH1. The hybrid plasmid pSD1, with a 2.8-kbp insert of chromosomal DNA at the BamHI site of pBR322, was subcloned into pUC19 to construct plasmid pSD3. The entire nucleotide sequence of an inserted PstI-BamHI fragment of plasmid pSD3 was determined by the dideoxy chain-termination method. Within this sequence, the mature enzyme protein-encoding sequence was found to start at a GTG initiation codon and to comprise 765 bp, as judged by comparison with the protein sequence. The deduced amino acid sequence of the enzyme indicated that the molecular weight is 26,778. The transformant of E. coli DH1 harboring pSD3 with a 1.8-kbp fragment showed about 200-fold-higher enzyme activity than the host. The enzyme was purified by a single chromatography step on DEAE-Toyopearl and obtained as crystals, with an activity yield of 39%. The purified enzyme was homogeneous, as judged by sodium dodecyl sulfate gel electrophoresis. The enzyme was most active at pH 8.5 and stable between pH 8 and 9. The enzyme was NAD+ dependent and had a pI of 4.3. The molecular mass was estimated to be 120 kDa by the gel filtration method and 28 kDa by electrophoresis, indicating that the enzyme exists in a tetrameric form.

  大肠杆菌HB101的7α-羟类固醇脱氢酶（EC 1.1.1.159）基因被克隆并在大肠杆菌DH1中表达。将含有2.8-kbp染色体DNA插入到pBR322的BamHI位点的杂交质粒pSD1亚克隆到pUC19中构建出质粒pSD3。通过dideoxy链终止法确定了质粒pSD3的插入PstI-BamHI片段的整个核苷酸序列。在该序列中，成熟酶蛋白编码序列从GTG启动密码子开始，由765个碱基组成，与蛋白质序列比较得出。酶的推导氨基酸序列表明分子量为26,778。携带1.8-kbp片段的大肠杆菌DH1转化体，其酶活性比宿主高约200倍。酶经DEAE-Toyopearl单一色谱步骤纯化，并以晶体形式获得，活性收率为39％。纯化的酶通过十二烷基硫酸钠凝胶电泳判断为均一。该酶在pH 8.5时最活跃，在pH 8和9之间稳定。该酶依赖于NAD+，其等电点为4.3。通过凝胶过滤法估计分子量为120 kDa，通过电泳法估计为28 kDa，表明该酶以四聚体形式存在。
• Hepatic reduction of the secondary bile acid 7-oxolithocholic acid is mediated by 11β-hydroxysteroid dehydrogenase 1
  作者：Alex Odermatt、Thierry Da Cunha、Carlos A. Penno、Charlie Chandsawangbhuwana、Christian Reichert、Armin Wolf、Min Dong、Michael E. Baker

  DOI：10.1042/bj20110022

  日期：2011.6.15

  The oxidized bile acid 7-oxoLCA (7-oxolithocholic acid), formed primarily by gut micro-organisms, is reduced in human liver to CDCA (chenodeoxycholic acid) and, to a lesser extent, UDCA (ursodeoxycholic acid). The enzyme(s) responsible remained unknown. Using human liver microsomes, we observed enhanced 7-oxoLCA reduction in the presence of detergent. The reaction was dependent on NADPH and stimulated by glucose 6-phosphate, suggesting localization of the enzyme in the ER (endoplasmic reticulum) and dependence on NADPH-generating H6PDH (hexose-6-phosphate dehydrogenase). Using recombinant human 11β-HSD1 (11β-hydroxysteroid dehydrogenase 1), we demonstrate efficient conversion of 7-oxoLCA into CDCA and, to a lesser extent, UDCA. Unlike the reversible metabolism of glucocorticoids, 11β-HSD1 mediated solely 7-oxo reduction of 7-oxoLCA and its taurine and glycine conjugates. Furthermore, we investigated the interference of bile acids with 11β-HSD1-dependent interconversion of glucocorticoids. 7-OxoLCA and its conjugates preferentially inhibited cortisone reduction, and CDCA and its conjugates inhibited cortisol oxidation. Three-dimensional modelling provided an explanation for the binding mode and selectivity of the bile acids studied. The results reveal that 11β-HSD1 is responsible for 7-oxoLCA reduction in humans, providing a further link between hepatic glucocorticoid activation and bile acid metabolism. These findings also suggest the need for animal and clinical studies to explore whether inhibition of 11β-HSD1 to reduce cortisol levels would also lead to an accumulation of 7-oxoLCA, thereby potentially affecting bile acid-mediated functions.

  主要由肠道微生物形成的氧化胆汁酸 7-oxoLCA（7-oxolithocholic acid）在人体肝脏中还原成 CDCA（chenodeoxycholic acid），其次是 UDCA（ursodeoxycholic acid）。负责该过程的酶仍然未知。利用人体肝脏微粒体，我们观察到 7-oxoLCA 在去污剂存在的情况下还原能力增强。该反应依赖于 NADPH，并受到 6-磷酸葡萄糖的刺激，这表明该酶定位在 ER（内质网）中，并依赖于 NADPH 生成的 H6PDH（己糖-6-磷酸脱氢酶）。利用重组人 11β-HSD1（11β-羟类固醇脱氢酶 1），我们证明了 7-oxoLCA 向 CDCA 的高效转化，以及 UDCA 的少量转化。与糖皮质激素的可逆代谢不同，11β-HSD1 只介导 7-oxoLCA 及其牛磺酸和甘氨酸共轭物的 7-oxo 还原。此外，我们还研究了胆汁酸对 11β-HSD1 依赖性糖皮质激素相互转化的干扰。7-OxoLCA 及其共轭物优先抑制了可的松的还原，而 CDCA 及其共轭物抑制了可的松的氧化。三维建模解释了所研究胆汁酸的结合模式和选择性。研究结果表明，11β-HSD1 在人体中负责 7-oxoLCA 的还原，这进一步证实了肝脏糖皮质激素激活与胆汁酸代谢之间的联系。这些发现还表明有必要进行动物和临床研究，以探讨抑制 11β-HSD1 以降低皮质醇水平是否也会导致 7-oxoLCA 的积累，从而可能影响胆汁酸介导的功能。
• Carboxyl-Terminal and Arg38 are Essential for Activity of the 7α-Hydroxysteroid Dehydrogenase from Clostridium absonum
  作者：Deshuai Lou、Bochu Wang、Jun Tan、Liancai Zhu

  DOI：10.2174/0929866521666140507160050

  日期：2014.7.18

  7α-hydroxysteroid dehydrogenase (7α-HSDH, EC 1.1.1.159), one of the short-chain dehydrogenase/reductase superfamily, catalyzes the dehydrogenation of C7 hydroxyl group of the steroid skeleton of bile acids. Clostridium absonum 7α-HSDH (Ca 7α-HSDH) was cloned and heterologously expressed in Escherichia coli. The function of carboxyterminal (C-terminal) and Arg38 of Ca 7α-HSDH was investigated through

  短链脱氢酶/还原酶超家族之一7α-羟基类固醇脱氢酶（7α-HSDH，EC 1.1.1.159）催化胆汁酸类固醇骨架C7羟基的脱氢。克隆了无性梭菌7α-HSDH（Ca7α-HSDH），并在大肠杆菌中异源表达。通过截短和定点诱变分别研究了Ca7α-HSDH的羧基末端（C末端）和Arg38的功能。当除去C末端的2个和6个氨基酸时，Ca7α-HSDH的催化效率（k（cat）/ K（m））分别保持19.1％和2.5％。此外，缺失8、14和17个氨基酸后无法检测到活性。用天冬氨酸置换第38位的精氨酸后，NADP（+）或NAD（+）的辅酶均未检测到活性。金属离子Mg（2+）（50 mM），Na（+）（200 mM）和K（+）（500 mM）可以分别最大程度地提高Ca7α-HSDH的活性61.4％，64.7％和105.7％。在4或25°C下孵育108小时后，活性没有明显变化，但在37°C下急剧下降。我们的
• The critical role of His48 in mouse cytosolic sulfotransferase SULT2A8 for the 7α-hydroxyl sulfation of bile acids
  作者：Takehiko Shimohira、Katsuhisa Kurogi、Ming-Cheh Liu、Masahito Suiko、Yoichi Sakakibara

  DOI：10.1080/09168451.2018.1464897

  日期：2018.8.3

  involved in the homeostasis of steroids and bile acids. SULT2A8, a 7α-hydroxyl bile acid-preferring mouse SULT, has been identified as the major enzyme responsible for the mouse-specific 7-O-sulfation of bile acids. Interestingly, SULT2A8 lacks a conservative catalytic His residue at position 99th. The catalytic mechanism underlying the SULT2A8-mediated 7-O-sulfation of bile acids thus remained unclear. In

  已知胞质磺基转移酶（SULT）SULT2A亚家族的成员严重参与类固醇和胆汁酸的稳态。SULT2A8是7α-羟基胆汁酸偏爱的小鼠SULT，已被确定为负责小鼠特异性7-O-胆汁酸硫酸化的主要酶。有趣的是，SULT2A8在第99位缺少保守的催化His残基。因此，尚不清楚SULT2A8介导的胆汁酸7-O-硫酸化的催化机理。在这项研究中，我们进行了突变分析，以便深入了解这个尚未解决的问题。获得的结果表明，两个氨基酸残基His48和Leu99对小鼠SULT2A8而言是唯一的，但对其他SULTs而言则不是，对于其对胆汁酸的7-O硫酸化活性至关重要。
• Miyazawa M.; Shindo M.; Shimada T., Drug Metab Dispos, 2001, 0090-9556, 200-5
  作者：Miyazawa M.、Shindo M.、Shimada T.

  DOI：——

  日期：——