Galangin O7-glucuronide | 463955-75-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: Galangin O7-glucuronide
• 英文别名: (2S,3S,4S,5R,6S)-6-(3,5-dihydroxy-4-oxo-2-phenylchromen-7-yl)oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 463955-75-1
• 化学式: C₂₁H₁₈O₁₁
• 分子量: 446.367
• InChiKey: RNIDRAZXQJUZTQ-JENRNSKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  183
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  高良姜素 、 uridine diphosphoglucuronic acid 在 recombinant human UDP-glucuronosyltransferase 1A₁ 作用下， 反应 1.0h， 生成 Galangin O3-glucuronide 、 Galangin O7-glucuronide
  参考文献：
  名称：

  Regioselective Glucuronidation of Flavonols by Six Human UGT1A Isoforms

  摘要：

  葡萄糖醛酸化是类黄酮生物利用度的主要障碍；了解其区域选择性和反应动力学会大大增强我们建模和预测类黄酮处置的能力。我们的目标是确定四种模型二苯乙烯酮在六种表达的人类UGT1A同工酶（UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10）作用下的区域选择性葡萄糖醛酸化。表征了六种UGT1A介导的四种二苯乙烯酮（均含7-OH基团）的体外反应动力学曲线；确定了动力学参数（Km, Vmax和CLint = Vmax/Km）。UGT1A1和1A3区域选择性地代谢7-OH基团，而UGT1A7, 1A8, 1A9和1A10更倾向于对3-OH基团进行葡萄糖醛酸化。UGT1A1和1A9是最有效的结合酶，其Km值≤1 μM，相对催化效率比≥5.5。UGT1A的葡萄糖醛酸化显示出惊人的强底物抑制作用。特别是，UGT1A1介导的代谢的Ksi值（底物抑制常数）小于5.4 μM。UGT1A同工酶显示出对二苯乙烯酮的3-OH和7-OH的不同位置偏好。3-O-和7-O-葡萄糖醛酸化的区分动力学特性表明（至少）催化域内存在两种不同的结合模式。多种结合模式的存在应提供更好的“专家”知识来建模和预测UGT1A介导的葡萄糖醛酸化。

  DOI：

  10.1007/s11095-011-0418-5

文献信息

• Regioselective Glucuronidation of Flavonols by Six Human UGT1A Isoforms
  作者：Baojian Wu、Beibei Xu、Ming Hu

  DOI：10.1007/s11095-011-0418-5

  日期：2011.8

  Glucuronidation is a major barrier to flavonoid bioavailability; understanding its regiospecificity and reaction kinetics would greatly enhance our ability to model and predict flavonoid disposition. We aimed to determine the regioselective glucuronidation of four model flavonols using six expressed human UGT1A isoforms (UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10). In vitro reaction kinetic profiles of six UGT1A-mediated metabolism of four flavonols (all with 7-OH group) were characterized; kinetic parameters (Km, Vmax and CLint = Vmax/Km) were determined. UGT1A1 and 1A3 regioselectively metabolized the 7-OH group, whereas UGT1A7, 1A8, 1A9 and 1A10 preferred to glucuronidate the 3-OH group. UGT1A1 and 1A9 were the most efficient conjugating enzymes with Km values of ≤1 μM and relative catalytic efficiency ratios of ≥5.5. Glucuronidation by UGT1As displayed surprisingly strong substrate inhibition. In particular, Ksi values (substrate inhibition constant) were less than 5.4 μM for UGT1A1-mediated metabolism. UGT1A isoforms displayed distinct positional preferences between 3-OH and 7-OH of flavonols. Differentiated kinetic properties between 3-O- and 7-O- glucuronidation suggested that (at least) two distinct binding modes within the catalytic domain were possible. The existence of multiple binding modes should provide better “expert” knowledge to model and predict UGT1A-mediated glucuronidation.

  葡萄糖醛酸化是类黄酮生物利用度的主要障碍；了解其区域选择性和反应动力学会大大增强我们建模和预测类黄酮处置的能力。我们的目标是确定四种模型二苯乙烯酮在六种表达的人类UGT1A同工酶（UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10）作用下的区域选择性葡萄糖醛酸化。表征了六种UGT1A介导的四种二苯乙烯酮（均含7-OH基团）的体外反应动力学曲线；确定了动力学参数（Km, Vmax和CLint = Vmax/Km）。UGT1A1和1A3区域选择性地代谢7-OH基团，而UGT1A7, 1A8, 1A9和1A10更倾向于对3-OH基团进行葡萄糖醛酸化。UGT1A1和1A9是最有效的结合酶，其Km值≤1 μM，相对催化效率比≥5.5。UGT1A的葡萄糖醛酸化显示出惊人的强底物抑制作用。特别是，UGT1A1介导的代谢的Ksi值（底物抑制常数）小于5.4 μM。UGT1A同工酶显示出对二苯乙烯酮的3-OH和7-OH的不同位置偏好。3-O-和7-O-葡萄糖醛酸化的区分动力学特性表明（至少）催化域内存在两种不同的结合模式。多种结合模式的存在应提供更好的“专家”知识来建模和预测UGT1A介导的葡萄糖醛酸化。