1,4-dihydroxynonene-glutathione conjugate | 208264-37-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1,4-dihydroxynonene-glutathione conjugate
• 英文别名: gamma-glutamyl-S-[2-hydroxy-1-(2-hydroxyethyl)heptyl]cysteinylglycine；(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-(1,4-dihydroxynonan-3-ylsulfanyl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
• CAS: 208264-37-3
• 化学式: C₁₉H₃₅N₃O₈S
• 分子量: 465.568
• InChiKey: CLEVVMDJDMEQKG-HESLUPGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  31
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  225
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1,4-dihydroxynonene-glutathione conjugate 在 镍 作用下， 生成 nonane-1,4-diol
  参考文献：
  名称：

  Analysis in the Rat of 4-Hydroxynonenal Metabolites Excreted in Bile: Evidence of Enterohepatic Circulation of These Byproducts of Lipid Peroxidation

  摘要：

  4-Hydroxynonenal (HNE) is a cytotoxic product resulting from the lipid peroxidation of membrane polyunsaturated fatty acids. In vitro, metabolism mainly leads to the corresponding alcohol (DHN), carboxylic acid (HNA), and the glutathione conjugate, whereas in vivo, mercapturic acid conjugates of HNE, DHN, HNA, and HNA-lactone and, more recently, dicarboxylic acids and related mercapturate conjugates were identified in urine of rats. In the study presented here, the identity of the HNE biotransformation products in the bile of rats following a single iv administration of [4-H-3]HNE and the potential for enterohepatic recycling of HNE metabolites were investigated. The identity of metabolites was assessed by comparison of their HPLC retention times with those of the corresponding synthesized standards and by mass spectrometry analysis. Five metabolites were present in the bile; two of them corresponded to HNE- and DHN-glutathione conjugates. Two others metabolites were identified as DHN- and HNA-lactone mercapturic acid conjugates. The fifth metabolite was isolated but remained unidentified. As previously observed for urinary elimination, the kinetic excretion of biliary metabolites exhibited a rapid metabolism of HNE in rats. Within 4 h of injection, the bile accounted for 19.5% (+/-2.8%) of the injected radioactivity, whereas only 3% was found in the feces within 48 h [Alary, J., et al. (1995) Chem. Res. Toxicol. 8, 34-39]. The extent of HNE enterohepatic recycling was estimated utilizing a modified version of the linked rat model in three animals. All rat recipients were found to have measurable levels of HNE metabolites in bile, confirming that HNE is likely to undergo enterohepatic recirculation in the rat. The extent of recycling was approximatly 7.7% of the total dose in this model. Two unknown metabolites were present in the bile of recipient rats and not found in the bile of donors rats, suggesting that intestinal microflora and/or intestinal mucosa could biotransform HNE-related compounds before or during the reabsorption process.

  DOI：

  10.1021/tx9900425
• 作为产物：
  描述：

  (E)-4-Hydroxy-2-nonenal 在 sodium tetrahydroborate 作用下， 以 phosphate buffer 为溶剂， 反应 13.0h， 生成 1,4-dihydroxynonene-glutathione conjugate
  参考文献：
  名称：

  Analysis in the Rat of 4-Hydroxynonenal Metabolites Excreted in Bile: Evidence of Enterohepatic Circulation of These Byproducts of Lipid Peroxidation

  摘要：

  4-Hydroxynonenal (HNE) is a cytotoxic product resulting from the lipid peroxidation of membrane polyunsaturated fatty acids. In vitro, metabolism mainly leads to the corresponding alcohol (DHN), carboxylic acid (HNA), and the glutathione conjugate, whereas in vivo, mercapturic acid conjugates of HNE, DHN, HNA, and HNA-lactone and, more recently, dicarboxylic acids and related mercapturate conjugates were identified in urine of rats. In the study presented here, the identity of the HNE biotransformation products in the bile of rats following a single iv administration of [4-H-3]HNE and the potential for enterohepatic recycling of HNE metabolites were investigated. The identity of metabolites was assessed by comparison of their HPLC retention times with those of the corresponding synthesized standards and by mass spectrometry analysis. Five metabolites were present in the bile; two of them corresponded to HNE- and DHN-glutathione conjugates. Two others metabolites were identified as DHN- and HNA-lactone mercapturic acid conjugates. The fifth metabolite was isolated but remained unidentified. As previously observed for urinary elimination, the kinetic excretion of biliary metabolites exhibited a rapid metabolism of HNE in rats. Within 4 h of injection, the bile accounted for 19.5% (+/-2.8%) of the injected radioactivity, whereas only 3% was found in the feces within 48 h [Alary, J., et al. (1995) Chem. Res. Toxicol. 8, 34-39]. The extent of HNE enterohepatic recycling was estimated utilizing a modified version of the linked rat model in three animals. All rat recipients were found to have measurable levels of HNE metabolites in bile, confirming that HNE is likely to undergo enterohepatic recirculation in the rat. The extent of recycling was approximatly 7.7% of the total dose in this model. Two unknown metabolites were present in the bile of recipient rats and not found in the bile of donors rats, suggesting that intestinal microflora and/or intestinal mucosa could biotransform HNE-related compounds before or during the reabsorption process.

  DOI：

  10.1021/tx9900425

文献信息

• Analysis in the Rat of 4-Hydroxynonenal Metabolites Excreted in Bile: Evidence of Enterohepatic Circulation of These Byproducts of Lipid Peroxidation
  作者：Alexia Laurent、Jacques Alary、Laurent Debrauwer、Jean-Pierre Cravedi

  DOI：10.1021/tx9900425

  日期：1999.10.1

  4-Hydroxynonenal (HNE) is a cytotoxic product resulting from the lipid peroxidation of membrane polyunsaturated fatty acids. In vitro, metabolism mainly leads to the corresponding alcohol (DHN), carboxylic acid (HNA), and the glutathione conjugate, whereas in vivo, mercapturic acid conjugates of HNE, DHN, HNA, and HNA-lactone and, more recently, dicarboxylic acids and related mercapturate conjugates were identified in urine of rats. In the study presented here, the identity of the HNE biotransformation products in the bile of rats following a single iv administration of [4-H-3]HNE and the potential for enterohepatic recycling of HNE metabolites were investigated. The identity of metabolites was assessed by comparison of their HPLC retention times with those of the corresponding synthesized standards and by mass spectrometry analysis. Five metabolites were present in the bile; two of them corresponded to HNE- and DHN-glutathione conjugates. Two others metabolites were identified as DHN- and HNA-lactone mercapturic acid conjugates. The fifth metabolite was isolated but remained unidentified. As previously observed for urinary elimination, the kinetic excretion of biliary metabolites exhibited a rapid metabolism of HNE in rats. Within 4 h of injection, the bile accounted for 19.5% (+/-2.8%) of the injected radioactivity, whereas only 3% was found in the feces within 48 h [Alary, J., et al. (1995) Chem. Res. Toxicol. 8, 34-39]. The extent of HNE enterohepatic recycling was estimated utilizing a modified version of the linked rat model in three animals. All rat recipients were found to have measurable levels of HNE metabolites in bile, confirming that HNE is likely to undergo enterohepatic recirculation in the rat. The extent of recycling was approximatly 7.7% of the total dose in this model. Two unknown metabolites were present in the bile of recipient rats and not found in the bile of donors rats, suggesting that intestinal microflora and/or intestinal mucosa could biotransform HNE-related compounds before or during the reabsorption process.