谷胱甘肽 | 70-18-8

• 物质功能分类: 原料药 - 专科用药 - 解毒药
• 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
• 中文名称: 谷胱甘肽
• 中文别名: 三缩氨基酸；还原型谷胱甘肽；5-L-谷氨酰-L-半胱氨酰甘氨酸；谷胱甘肽(还原型)；硫糠质；还原谷胱甘肽；L-还原型谷胱甘肽；谷胱甘肽还原型；麸氨基硫；L-谷胱甘肽；还原型谷胱苷肽；谷光甘肽
• 英文名称: GLUTATHIONE
• 英文别名: GSH；L-glutathione；reduced glutathione；L-GSH；L-glutathione reduced；γ-glutamylcysteinylglycine；glutathione (reduced)；γ-Glu-Cys-Gly；gluthathione；glutatione；γ-L-glutamyl-L-cysteinylglycine；(2S)-2-azaniumyl-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoate
• CAS: 70-18-8
• 化学式: C₁₀H₁₇N₃O₆S
• mdl: MFCD00065939
• 分子量: 307.327
• InChiKey: RWSXRVCMGQZWBV-WDSKDSINSA-N

物化性质

• 熔点：
  192-195 °C (dec.) (lit.)
• 比旋光度：
  -16.5 º (c=2, H2O)
• 沸点：
  754.5±60.0 °C(Predicted)
• 密度：
  1.4482 (rough estimate)
• 溶解度：
  H2O:50 mg/mL
• LogP：
  -1.645 (est)
• 物理描述：
  Solid
• 碰撞截面：
  167.4 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  -4.5
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  160
• 氢给体数：
  6
• 氢受体数：
  8

ADMET

毒理性

• 毒性总结

谷胱甘肽（GSH）参与白三烯的合成，并且是谷胱甘肽过氧化物酶的辅因子。它还作为一种亲水性分子，在肝脏的生物转化过程中被添加到亲脂性毒素和废物中，之后它们才能成为胆汁的一部分。谷胱甘肽也用于解毒甲基乙二醛，这是一种代谢副产品产生的毒素。这种解毒反应由糖氧酸酶系统完成。糖氧酸酶I催化甲基乙二醛和还原型谷胱甘肽转化为S-D-乳酰谷胱甘肽。糖氧酸酶II催化S-D-乳酰谷胱甘肽转化为还原型谷胱甘肽和D-乳酸。GSH在由细胞质、微体和线粒体中的谷胱甘肽S-转移酶酶催化的结合反应和还原反应中作为辅因子而闻名。然而，它能够参与与非酶结合的一些化学物质，据推测它与N-乙酰-p-苯醌亚胺（NAPQI）有相当程度的结合，NAPQI是由对乙酰氨基酚过量中毒形成的活性细胞色素P450的活性代谢物。在这种能力下，谷胱甘肽作为自杀底物与NAPQI结合，并在过程中解毒它，取代了否则会被有毒加合的细胞蛋白巯基团。对于这种过量的首选医疗治疗方法，在文献中一直得到支持的是雾化形式的N-乙酰半胱氨酸的给药，细胞用它来替换消耗的GSSG并允许一个可用的GSH池。

Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II catalyzes the conversion of S-D-Lactoyl Glutathione to Reduced Glutathione and D-lactate. GSH is known as a cofactor in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is capable of participating in non-enzymatic conjugation with some chemicals, as it is hypothesized to do to a significant extent with n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450 reactive metabolite formed by toxic overdose of acetaminophen. Glutathione in this capacity binds to NAPQI as a suicide substrate and in the process detoxifies it, taking the place of cellular protein sulfhydryl groups which would otherwise be toxically adducted. The preferred medical treatment to an overdose of this nature, whose efficacy has been consistently supported in literature, is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and allow a usable GSH pool.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

研究表明，谷胱甘肽口服不具有生物活性，而且口服谷胱甘肽片剂或胶囊实际上被身体吸收的量非常少。

Research suggests that glutathione is not orally bioactive, and that very little of oral glutathione tablets or capsules is actually absorbed by the body.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性数据

奥尔德-小鼠 LD50 5000 mg/kg，IPR-小鼠 LD50 4020 mg/kg，SCU-小鼠 LD50 5000 mg/kg，IVN-大鼠 LD50 > 2000 mg/kg，IMS-小鼠 LD50 4000 mg/kg。

ORL-MUS LD₅₀ 5000 mg/kg, IPR-MUS LD₅₀ 4020 mg/kg, SCU-MUS LD₅₀ 5000 mg/kg, IVN-RBT LD₅₀ > 2000 mg/kg, IMS-MUS LD₅₀ 4000 mg/kg

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

研究表明，谷胱甘肽口服不具有生物活性，而且口服谷胱甘肽片剂或胶囊实际上被身体吸收的量非常少。

Research suggests that glutathione is not orally bioactive, and that very little of oral glutathione tablets or capsules is actually absorbed by the body.

来源:DrugBank

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xi
• 安全说明：
  S24/25
• 危险类别码：
  R68
• WGK Germany：
  2
• 海关编码：
  2930909090
• 危险品运输编号：
  NONH for all modes of transport
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312+P330,P302+P352,P304+P340+P312,P305+P351+P338,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

根据提供的信息,关于谷胱甘肽的一些重要点如下:

1. 谷胱甘肽是体内重要的抗氧化物质和解毒剂。

2. 它主要在肝脏中含量丰富,对保护肝细胞膜、促进肝酶活性有重要作用。

3. 可用于治疗重金属、丙烯腈、氟化物等中毒。

4. 具有抗氧化、清除自由基、解毒等多种生物功能。

5. 通过与有毒物质结合发挥解毒作用。

6. 在细胞代谢中可还原活性氧,保护细胞免受氧化损伤。

7. 可用于延缓衰老、抗癌、增强免疫力等。

8. 制备方法主要有溶剂萃取法、酶法、发酵法和化学合成法。

9. 目前主要从高含量谷胱甘肽的酵母中提取。

10. 质量要求包括纯度≥98%,醋酸根≤12%,水分≤8%等指标。

反应信息

• 作为反应物：
  描述：

  谷胱甘肽 在 扑湿痛 作用下， 以 aq. phosphate buffer 、 乙醇 、 水 为溶剂， 生成 L-胱氨酸
  参考文献：
  名称：

  谷胱甘肽和 N-乙酰基-L-半胱氨酸存在下甲芬那酸过量毒性机制的电化学证据

  摘要：

  In this study, the electrochemical oxidation of mefenamic acid was investigated in the presence of glutathione and N-acetyl-L-cysteine. The results revealed that the mefenamic acid was involved in a catalytic reaction with glutathione and N-acetyl-L-cysteine. This investigation presents some electrochemical evidence for the mechanism of action of these compounds in mefenamic acid poisoning. (c) 2020 The Electrochemical Society ("ECS"). Published on behalf of ECS by IOP Publishing Limited.

  DOI：

  10.1149/1945-7111/ab76b6
• 作为产物：
  描述：

  N⁸-Mono-glutathionylspermidine 在 Trypanosoma brucei trypanothione synthetase 作用下， 以 aq. buffer 为溶剂， 生成 谷胱甘肽
  参考文献：
  名称：

  Dissecting the Catalytic Mechanism of Trypanosoma brucei Trypanothione Synthetase by Kinetic Analysis and Computational Modeling

  摘要：

  In pathogenic trypanosomes, trypanothione synthetase (TryS) catalyzes the synthesis of both glutathionylspermidine (Gsp) and trypanothione (bis(glutathionyl) spermidine (T(SH)(2))). Here we present a thorough kinetic analysis of Trypanosoma brucei TryS in a newly developed phosphate buffer system at pH 7.0 and 37 degrees C, mimicking the physiological environment of the enzyme in the cytosol of bloodstream parasites. Under these conditions, TryS displays K-m values for GSH, ATP, spermidine, and Gsp of 34, 18, 687, and 32 mu M, respectively, as well as K-i values for GSH and T(SH) 2 of 1 mM and 360 mu M, respectively. As Gsp hydrolysis has a K-m value of 5.6 mM, the in vivo amidase activity is probably negligible. To obtain deeper insight in the molecular mechanism of TryS, we have formulated alternative kinetic models, with elementary reaction steps represented by linear kinetic equations. The model parameters were fitted to the extensive matrix of steady-state data obtained for different substrate/product combinations under the in vivo-like conditions. The best model describes the full kinetic profile and is able to predict time course data that were not used for fitting. This system's biology approach to enzyme kinetics led us to conclude that (i) TryS follows a ter-reactant mechanism, (ii) the intermediate Gsp dissociates from the enzyme between the two catalytic steps, and (iii) T(SH)(2) inhibits the enzyme by remaining bound at its product site and, as does the inhibitory GSH, by binding to the activated enzyme complex. The newly detected concerted substrate and product inhibition suggests that TryS activity is tightly regulated.

  DOI：

  10.1074/jbc.m113.483289
• 作为试剂：
  描述：

  dehydrodiconiferyl alcohol 在 谷胱甘肽 、 LigE type beta etherase from Agrobacterium sp. 作用下， 以 aq. phosphate buffer 为溶剂， 生成 、 、
  参考文献：
  名称：

  苯基香豆糖 β-5 木质素模型化合物和农杆菌属 LigE 型醚酶催化的聚合物木质素的醚键裂解。

  摘要：

  一种来自木质素降解农杆菌属的 LigE 型 β-醚酶。发现通过谷胱甘肽在 α 位反应，将苯基香马兰 β-5 木质素二聚体转化为顺式二苯乙烯、烯烃和酮产物，这是醚酶攻击 β-5 单元α位的第一个例子。

  DOI：

  10.1002/cbic.202400132

文献信息

• [EN] HYPERVALENT IODINE CF2CF2X REAGENTS AND THEIR USE<br/>[FR] RÉACTIFS CF2CF2X À BASE D'IODE HYPERVALENT ET LEUR UTILISATION
  申请人：ETH ZUERICH

  公开号：WO2016019475A1

  公开（公告）日：2016-02-11

  A hypervalent iodine of formula (I) or formula (II) wherein R is a nucleophile and a method for their production is described. Such compounds can be used for fluoroethylation of compounds carrying a reactive group. A preferred compound carrying a reactive group is cystein in any environment such as peptide targets.

  一种具有化学式（I）或化学式（II）的高价碘，其中R是亲核试剂，并描述了它们的生产方法。这类化合物可用于对携带反应基团的化合物进行氟乙基化。携带反应基团的优选化合物是半胱氨酸，可存在于任何环境中，如肽靶标。
• Rethinking Cysteine Protective Groups:<i>S</i>-Alkylsulfonyl-<scp>l</scp>-Cysteines for Chemoselective Disulfide Formation
  作者：Olga Schäfer、David Huesmann、Christian Muhl、Matthias Barz

  DOI：10.1002/chem.201604391

  日期：2016.12.12

  The ability to reversibly cross‐link proteins and peptides grants the amino acid cysteine its unique role in nature as well as in peptide chemistry. We report a novel class of S‐alkylsulfonyl‐l‐cysteines and N‐carboxy anhydrides (NCA) thereof for peptide synthesis. The S‐alkylsulfonyl group is stable against amines and thus enables its use under Fmoc chemistry conditions and the controlled polymerization

  可逆性交联蛋白质和多肽的能力使氨基酸半胱氨酸在自然界以及多肽化学中具有独特的作用。我们报告了一类新型的S-烷基磺酰基-L-半胱氨酸和N-羧基酐（NCA）用于肽合成。该小号烷基磺酰基是针对胺稳定的，因此使它的Fmoc化学条件和相应的种NCA屈服良好定义的均聚物以及嵌段共聚物的受控聚合下使用。然而，硫醇会立即与S反应-烷基磺酰基形成不对称的二硫化物。因此，我们引入了第一个反应性半胱氨酸衍生物，以在合成多肽中有效和化学选择性地形成二硫化物，从而绕开了其他保护基团的裂解步骤。
• Of Thiols and Disulfides: Methods for Chemoselective Formation of Asymmetric Disulfides in Synthetic Peptides and Polymers
  作者：Olga Schäfer、Matthias Barz

  DOI：10.1002/chem.201800681

  日期：2018.8.22

  media to form S−C bonds, possibilities for the chemoselective formation of asymmetric disulfides have been less approached. Focusing on bioreversibility in conjugation chemistry, the formation of disulfide bonds is highly desirable for the attachment of thiol‐containing bioactive agents to proteins or in cross‐linking reactions, because disulfide bonds can combine stability in blood with degradability inside

  在蛋白质或肽化学中，硫醇经常被选作化学选择性修饰反应的化学实体。尽管这是解决在水性介质中形成半胱氨酸键的半胱氨酸和高半胱氨酸的成熟方法，但是，化学选择性形成不对称二硫键的可能性却很少。关注共轭化学中的生物可逆性，对于将含硫醇的生物活性剂连接到蛋白质或进行交联反应而言，形成二硫键是非常可取的，因为二硫键可以将血液中的稳定性与细胞内的可降解性结合在一起。在此概念文章中，重点介绍了肽和聚合物材料中掺入的巯基部分的活化基团领域中的最新方法。探索了在材料合成过程中对硫醇具有高反应性的稳定性的有利组合，其重点在于简化和防止副反应以及在二硫化物形成之前进行的其他脱保护和活化步骤。此外，突出了这种化学的应用，并展望了未来的前景。
• [EN] SULFINYLPYRIDINES AND THEIR USE IN THE TREATMENT OF CANCER<br/>[FR] SULFINYLPYRIDINES ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：OBLIQUE THERAPEUTICS AB

  公开号：WO2018146468A1

  公开（公告）日：2018-08-16

  There is provided compounds of formula I (I) or pharmaceutically-acceptable salts thereof, wherein L, R1, R2, R3, R4 and n have meanings provided in the description, which compounds are useful in the treatment of cancers.

  提供了式I（I）的化合物或其药用盐，其中L、R1、R2、R3、R4和n的含义如描述中所提供，这些化合物在治疗癌症方面是有用的。
• Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20150231142A1

  公开（公告）日：2015-08-20

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及含有上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。

表征谱图