L-glutamic acid sodium salt monohydrate | 142-47-2

• 物质功能分类: 生物化工 - 常见氨基酸及蛋白质类
• 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: L-glutamic acid sodium salt monohydrate
• 英文别名: sodium (2S)-2-amino-5-hydroxy-5-oxopentanoate hydrate；L-glutamic acid monosodium salt monohydrate；monosodium glutamate hydrate；monosodium L-glutamate monohydrate；monosodium Glutamate Monohydrate；sodium glutamate monohydrate；Monosodium glutamate monohydrate；sodium;(2S)-2-aminopentanedioate;hydron;hydrate
• CAS: 142-47-2；6106-04-3
• 化学式: C₅H₈NO₄*H₂O*Na
• 分子量: 187.128
• InChiKey: GJBHGUUFMNITCI-QTNFYWBSSA-M

物化性质

• 熔点：
  232°C
• 比旋光度：
  20 -3.5° (10% soln in 5° Bé HCl); D20 +25.16° (10g MSG/100ml 2N HCl)
• 密度：
  d20 (saturated water soln): 1.620
• 溶解度：
  易溶于水；微溶于乙醇(95%)。
• LogP：
  -1.44
• 物理描述：
  Monosodium glutamate appears as white or off-white crystalline powder with a slight peptone-like odor. pH (0.2% solution)7.0. (NTP, 1992)
• 颜色/状态：
  White free flowing crystals or crystalline powder
• 气味：
  Practically odorless
• 味道：
  Meaty taste comes from contaminants in crude glutamates; sweet-saline taste in large concn; no flavor in small quantity
• 沸点：
  225 °C (decomposes)
• 旋光度：
  Specific optical rotation: +24.2 to +25.5 deg at 25 °C/D (concn = 8.0 g in 100 mL 1.0 N hydrochloric acid)
• 分解：
  When heated to decomposition it emits toxic fumes of oxides of /nitrogen and sodium oxide/.

计算性质

• 辛醇/水分配系数(LogP)：
  -5.89
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

ADMET

代谢

谷氨酸在组织中通过氧化脱氨代谢...或者通过丙酮酸的转氨作用产生草酸乙酸...然后通过α-酮戊二酸进入柠檬酸循环...。谷氨酸代谢的量虽然较小，但在生理上重要的途径包括脱羧生成γ-氨基丁酸（GABA）和酰胺化生成谷氨酰胺...。脱羧生成GABA依赖于吡哆醛磷酸，它是谷氨酸脱羧酶的辅酶...，谷氨酸转氨酶也是如此。维生素B6缺乏的大鼠血清谷氨酸水平升高，谷氨酸清除延迟...。/谷氨酸/

Glutamic acid is metabolized in the tissues by oxidative deamination ... or by transamination with pyruvate to yield oxaloacetic acid ... which, via alpha-ketoglutarate, enters the citric acid cycle ... .. Quantitatively minor but physiologically important pathways of glutamate metabolism involve decarboxylation to gamma-aminobutyrate (GABA) and amidation to glutamine ... . Decarboxylation to GABA is dependent on pyridoxal phosphate, a coenzyme of glutamic acid decarboxylase ..., as is glutamate transaminase. Vitamin B6-deficient rats have elevated serum glutamate levels and delayed glutamate clearance ... . /Glutamic acid/

来源:Hazardous Substances Data Bank (HSDB)

代谢

口服给大鼠1克/千克的谷氨酸钠后，仅观察到血浆焦谷氨酸水平的小幅上升。在这些条件下，没有观察到焦谷氨酸或谷氨酸在大脑水平上的增加。

Oral dose of 1 g/kg monosodium glutamate given to rats was followed by only a small rise in plasma pyroglutamate levels. No incr of pyroglutamate or glutamate brain levels was observed under these conditions.

来源:Hazardous Substances Data Bank (HSDB)

代谢

谷氨酸在组织中通过氧化脱氨代谢...或者通过与丙酮酸进行转氨作用产生草酸醋酸...，通过α-酮戊二酸进入柠檬酸循环...。谷氨酸代谢的量虽然较少，但在生理上重要的途径包括脱羧生成γ-氨基丁酸（GABA）和酰胺化生成谷氨酰胺...。脱羧生成GABA依赖于吡哆醛磷酸，它是谷氨酸脱羧酶的辅酶...，谷氨酸转氨酶也是如此。维生素B6缺乏的大鼠血清谷氨酸水平升高，谷氨酸清除延迟...。/谷氨酸/

Glutamic acid is metabolized in the tissues by oxidative deamination ... or by transamination with pyruvate to yield oxaloacetic acid ... which, via alpha-ketoglutarate, enters the citric acid cycle ... .. Quantitatively minor but physiologically important pathways of glutamate metabolism involve decarboxylation to gamma-aminobutyrate (GABA) and amidation to glutamine ... . Decarboxylation to GABA is dependent on pyridoxal phosphate, a coenzyme of glutamic acid decarboxylase ..., as is glutamate transaminase. Vitamin B6-deficient rats have elevated serum glutamate levels and delayed glutamate clearance ... . /Glutamic acid/

来源:Hazardous Substances Data Bank (HSDB)

代谢

口服给大鼠1克/千克的谷氨酸钠后，仅观察到血浆焦谷氨酸水平的小幅上升。在这些条件下，没有观察到焦谷氨酸或谷氨酸在大脑水平上的增加。

Oral dose of 1 g/kg monosodium glutamate given to rats was followed by only a small rise in plasma pyroglutamate levels. No incr of pyroglutamate or glutamate brain levels was observed under these conditions.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

谷氨酸钠（MSG）通过腹膜内给药（持续10天，剂量为4 mg/g体重）显著增加了大鼠肝脏、肾脏和大脑中的丙二醛（MDA）形成。同时给予维生素C、维生素E和槲皮素给接受MSG处理的大鼠，显著减少了由MSG引起的MDA增加。维生素E主要在肝脏减少脂质过氧化，其次是维生素C，然后是槲皮素，而维生素C和槲皮素在保护大脑免受膜损伤方面比维生素E表现出更大的能力。MSG在三个器官中引起的谷胱甘肽（GSH）水平降低与谷胱甘肽-S-转移酶（GST）活性的显著增加相对应。虽然MSG在肝脏中增加了超氧化物歧化酶和过氧化氢酶的活性（p < 0.001），但在肾脏和大脑中显著降低了这些酶的活性。这三种抗氧化剂在改善MSG对三个器官中GSH水平和酶的影响方面是有效的。虽然MSG增加了大鼠肝脏和肾脏中葡萄糖-6-磷酸酶的活性（p < 0.001），但大脑中该酶的活性极低。在接受MSG处理的大鼠中，丙氨酸转氨酶、天冬氨酸转氨酶和γ-谷氨酰转移酶的活性显著增加。测试的抗氧化剂显著保护了免受MSG诱导的肝脏毒性。4 mg/g剂量的MSG显著（p < 0.01）诱导了微核多色红细胞（MNPCEs）的形成。维生素C和槲皮素共同治疗抑制了MSG诱导的MNPCEs的形成（p < 0.001）...

Monosodium glutamate (MSG) administered intraperitoneally /for 10 days/ at a dose of 4 mg/g bw markedly increase malondialdehyde (MDA) formation in the liver, the kidney and brain of rats. Simultaneous administration of VIT C, VIT E and quercetin to MSG-treated rats significantly reduced this increase in MDA induced by MSG. VIT E reduced lipid peroxidation mostly in the liver followed by VIT C and then quercetin, while VIT C and quercetin showed a greater ability to protect the brain from membrane damage than VIT E. The decreased glutathione (GSH) level elicited by MSG in the three organs corresponded with marked increase in the activity of glutathione-S-transferase (GST). While MSG increased (p < 0.001) the activities of superoxide dismutase and catalase in the liver, it decreased significantly the activities of these enzymes in the kidney and the brain. The three antioxidants were effective at ameliorating the effects of MSG on GSH levels and the enzymes in the three organs examined. While MSG increased the activity of glucose-6-phosphatase in the liver and kidneys of rats (p < 0.001), the activity of the enzyme was abysmally low in the brain. There were marked increases in the activities of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase in rats treated with MSG. The antioxidants tested protected against MSG-induced liver toxicity significantly. MSG at a dose of 4 mg/g significantly (p < 0.01) induced the formation of micronucleated polychromatic erythrocytes (MNPCEs). Co-treatment of rats with VIT C and quercetin inhibited the induction of MNPCEs by MSG (p < 0.001) ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

谷氨酸及其铵盐、钙盐、单钠盐和钾盐在1988年由联合粮农组织/世界卫生组织食品添加剂专家委员会（JECFA）进行了评估。委员会注意到，只有在通过灌胃给予极高剂量（>30mg/kg体重）后，肠道和肝脏的代谢才会导致系统性循环中水平的升高。摄入单钠谷氨酸（MSG）与母体乳汁中水平升高无关，谷氨酸不易通过胎盘屏障。人类婴儿对谷氨酸的代谢与成人相似。使用MSG通过饮食给药进行的常规毒性研究，在多个物种中并未发现任何特定的毒性或致癌作用，也没有在生殖和畸胎学研究中发现任何不良结果。注意到在通过注射给药或作为灌胃给予极高剂量的结果，在几个物种中产生了中枢神经系统损伤。比较研究显示，新生小鼠对神经元损伤最为敏感；年龄较大的动物和其他物种（包括灵长类）则较不敏感。即使在饮用水中一次性给予10克MSG的剂量，人类血液中的谷氨酸水平也未达到与新生小鼠下丘脑损伤相关的水平。由于人类研究未能证实MSG与“中国餐馆综合症”或其他特异不耐性有关，JECFA为谷氨酸及其盐类分配了一个“未指定可接受日摄入量（ADI）”。对婴儿没有额外的风险。欧洲委员会的科学委员会（SCF）在1991年得出了类似的评估结论。美国实验生物学联合会（FASEB）和联邦药物管理局（FDA）的后续审查结论并没有排除敏感亚群体的存在，但其他方面则与JECFA和SCF的安全性评估一致。

L-Glutamic acid and its ammonium, calcium, monosodium and potassium salts were evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1988. The Committee noted that intestinal and hepatic metabolism results in elevation of levels in systemic circulation only after extremely high doses given by gavage (>30mg/kg body weight). Ingestion of monosodium glutamate (MSG) was not associated with elevated levels in maternal milk, and glutamate did not readily pass the placental barrier. Human infants metabolized glutamate similarly to adults. Conventional toxicity studies using dietary administration of MSG in several species did not reveal any specific toxic or carcinogenic effects nor were there any adverse outcomes in reproduction and teratology studies. Attention was paid to central nervous system lesions produced in several species after parenteral administration of MSG or as a consequence of very high doses by gavage. Comparative studies indicated that the neonatal mouse was most sensitive to neuronal injury; older animals and other species (including primates) were less so. Blood levels of glutamate associated with lesions of the hypothalamus in the neonatal mouse were not approached in humans even after bolus doses of 10 g MSG in drinking water. Because human studies failed to confirm an involvement of MSG in "Chinese Restaurant Syndrome" or other idiosyncratic intolerance, the JECFA allocated an "acceptable daily intake (ADI) not specified" to glutamic acid and its salts. No additional risk to infants was indicated. The Scientific Committee for Food (SCF) of the European Commission reached a similar evaluation in 1991. The conclusions of a subsequent review by the Federation of American Societies for Experimental Biology (FASEB) and the Federal Drug Administration (FDA) did not discount the existence of a sensitive subpopulation but otherwise concurred with the safety evaluation of JECFA and the SCF.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP 特异性反应/：没有报告去污染措施。不存在解毒剂。支持性措施：如果胸部疼痛持续，进行心电图和心脏评估。提醒患者避免食用含有MSG（味精）的食物。

/SRP Idiosyncratic reaction/: No decontamination measures have been reported. No antidotes exist. Supportive measures: Follow with ECG and cardiac evaluation if chest pain persists. Alert patient to avoid foods with MSG.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人类暴露研究/ ... 在6名健康对照和30名哮喘患者（7名：过敏性哮喘；15名：阿司匹林不耐受的内在性哮喘；8名：阿司匹林不耐受、酒精或食物添加剂不耐受的内在性哮喘）中测试了2.5克的高剂量。两名患者在摄入后6至10小时出现轻度支气管痉挛。讨论了不同的机制。可能涉及胆碱能机制，要么是由于乙酰胆碱合成的刺激，要么是由于反流性食管炎引起的迷走神经反射。然而，似乎需要高迷走神经高反应性才能发生哮喘。结论是，如果摄入高剂量，极少数内在性哮喘患者可能会对单钠谷氨酸不耐受。

/HUMAN EXPOSURE STUDIES/ ... A high dose of 2.5 g was tested in 6 healthy controls and 30 asthmatics (7: allergic asthma; 15: intrinsic asthma with intolerance to aspirin; 8: intrinsic asthma with aspirin intolerance, intolerance to alcohol or to food additives). Two patients presented with a mild bronchospasm, occurring 6 to 10 hours after the ingestion. Different mechanisms are discussed. A cholinergic mechanism might be incriminated, either due to stimulation of the synthesis of acetylcholine, or due to a vagal reflex elicited by a reflux esophagitis. However, a high vagal hyperreactivity seems to be needed for the occurrence of asthma. It is concluded that a very small subset of patients with intrinsic asthma might present with an intolerance to monosodium glutamate if high doses are consumed.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/人体暴露研究/MSG（谷氨酸钠）被广泛认为是导致“中国餐馆综合症”的诱因，其中潮红被认为是反应的一部分。六名受试者通过激光多普勒流速仪监测了在MSG及其环化产物焦谷氨酸挑战期间面部皮肤血流的变化。此外，还审查了在实验室接受MSG挑战的患者的记录。在测试的二十四人中，没有引起潮红，其中十八人曾有过中国餐馆综合症潮红的历史。这些结果表明，如果MSG引起的潮红确实存在，也一定非常罕见。MSG及其环化产物焦谷氨酸可能会引起水肿和相关症状。

/HUMAN EXPOSURE STUDIES/ Monosodium glutamate is widely regarded as the provocative agent in the "Chinese restaurant syndrome," of which flushing is regarded as part of the reaction. Six subjects were monitored by laser Doppler velocimetry for changes in facial cutaneous blood flow during challenge with monosodium glutamate and its cyclization product, pyroglutamate. Additionally, records of patients challenged with monosodium glutamate in the laboratory were reviewed. No flushing was provoked among the twenty four people tested, eighteen of whom gave a positive history of Chinese restaurant syndrome flushing. These results indicate that monosodium glutamate provoked flushing, if it exists at all, must be rare. Monosodium glutamate and its cyclization product, pyroglutamate, may provoke edema and associated symptoms.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

谷氨酸通过一种对氨基酸特异性的主动转运系统从肠道吸收。这一过程是可饱和的，可以被竞争性抑制，并且依赖于钠离子浓度...在肠道吸收过程中，大量谷氨酸发生转氨作用，因此门静脉血液中的丙氨酸水平升高。如果摄入大量的谷氨酸，门静脉谷氨酸水平会上升...这种升高导致肝脏对谷氨酸的代谢增加，从而释放出葡萄糖、乳酸、谷氨酰胺和其他氨基酸进入系统循环...谷氨酸的药代动力学取决于它是自由的还是结合在蛋白质中，以及是否存在其他食物成分。肠道腔内和刷状缘的蛋白质消化产生小肽和氨基酸的混合物；二肽和三肽可能进入吸收细胞，细胞内可能发生水解，释放出更多的氨基酸。氨基酸和肽转运的缺陷是已知的...饮食蛋白中的谷氨酸和分泌到肠道中的内源蛋白一起被消化成自由的氨基酸和小肽，两者都被吸收到粘膜细胞中，其中肽被水解成自由的氨基酸，部分谷氨酸被代谢。过量的谷氨酸和其他氨基酸出现在门静脉血液中。由于肠道粘膜细胞和肝脏中谷氨酸的快速代谢，即使摄入大量饮食蛋白后，系统血浆水平也保持低。/谷氨酸/

Glutamate is absorbed from the gut by an active transport system specific for amino acids. This process is saturable, can be competitively inhibited, and is dependent on sodium ion concentration... . During intestinal absorption, a large proportion of glutamic acid is transaminated and consequently alanine levels in portal blood are elevated. If large amounts of glutamate are ingested, portal glutamate levels increase ... . This elevation results in increased hepatic metabolism of glutamate, leading to release of glucose, lactate, glutamine, and other amino acids, into systemic circulation ... . The pharmacokinetics of glutamate depend on whether it is free or incorporated into protein, and on the presence of other food components. Digestion of protein in the intestinal lumen and at the brush border produces a mixture of small peptides and amino acids; di-and tri-peptides may enter the absorptive cells where intracellular hydrolysis may occur, liberating further amino acids. Defects are known in both amino acid and peptide transport ... .. Glutamic acid in dietary protein, together with endogenous protein secreted into the gut, is digested to free amino acids and small peptides, both of which are absorbed into mucosal cells where peptides are hydrolyzed to free amino acids and some of the glutamate is metabolized. Excess glutamate and other amino acids appear in portal blood. As a consequence of the rapid metabolism of glutamate in intestinal mucosal cells and in the liver, systemic plasma levels are low, even after ingestion of large amounts of dietary protein. /Glutamic acid/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

肠道和肝脏代谢导致仅在通过灌胃给予极高剂量（>30mg/kg体重）后，系统循环中的水平升高。摄入单钠谷氨酸（MSG）与母体乳汁中水平升高无关，且谷氨酸不易通过胎盘屏障。人类婴儿对谷氨酸的代谢方式与成人相似。

... Intestinal and hepatic metabolism results in elevation of levels in systemic circulation only after extremely high doses given by gavage (>30mg/kg body weight). Ingestion of monosodium glutamate (MSG) was not associated with elevated levels in maternal milk, and glutamate did not readily pass the placental barrier. Human infants metabolized glutamate similarly to adults.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服药理上高剂量的谷氨酸会导致血浆水平升高。血浆中谷氨酸的峰值水平既取决于剂量也取决于浓度……当相同剂量（1克/千克体重）的谷氨酸钠（MSG）通过灌胃的方式以水溶液给予新生大鼠时，将浓度从2%增加到10%会导致血浆下曲线面积增加五倍；在 mice中也观察到了类似的结果……相反，当MSG（1.5克/千克体重）以2%至20% w/v的不同浓度通过灌胃给予43天大的小鼠时，无法建立血浆水平与浓度之间的相关性……

Oral administration of pharmacologically high doses of glutamate results in elevated plasma levels. The peak plasma glutamate levels are both dose and concentration dependent ... . When the same dose (1 g/kg b.w.) of monosodium glutamate (MSG) was administered by gavage in aqueous solution to neonatal rats, increasing the concentration from 2% to 10% caused a five-fold increase in the plasma area under curve; similar results were observed in mice ... . Conversely, when MSG (1.5 g/kg b.w.) was administered to 43-day-old mice by gavage at varying concentrations of 2 to 20% w/v, no correlation could be established between plasma levels and concentration ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

以10% w/v溶液形式通过灌胃给予1 g/kg b.w. MSG的标准剂量，导致所有研究物种的血浆谷氨酸含量显著增加。在所有物种中，成年猴子的血浆谷氨酸峰值水平最低（是禁食水平的6倍），而在小鼠中最高（是禁食水平的12-35倍）。观察到新生儿和成年之间的年龄差异；在小鼠和 rats 中，婴儿的血浆峰值水平和曲线下面积高于成年人，而在 guinea pigs 中则观察到相反的情况。

Administration of a standard dose of 1 g/kg b.w. MSG by gavage as a 10% w/v solution resulted in a marked increase of plasma glutamate in all species studied. Peak plasma glutamate levels were lowest in adult monkeys (6 times fasting levels) and highest in mice (12-35 times fasting levels). Age-related differences between neonates and adults were observed; in mice and rats, peak plasma levels and area under curve were higher in infants than in adults while in guinea pigs the converse was observed.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

谷氨酸通过一种对氨基酸特异性的主动运输系统从肠道吸收。这一过程是可饱和的，可以被竞争性抑制，并且依赖于钠离子浓度……在肠道吸收过程中，大量谷氨酸发生转氨作用，因此门脉血液中的丙氨酸水平升高。如果摄入大量的谷氨酸，门脉血液中的谷氨酸水平会升高……这种升高导致肝脏对谷氨酸的代谢增加，进而释放葡萄糖、乳酸、谷氨酰胺和其他氨基酸进入系统循环……谷氨酸的药代动力学取决于它是自由的还是结合在蛋白质中，以及是否存在其他食物成分。肠道腔内和刷状缘的蛋白质消化产生小肽和氨基酸的混合物；二肽和三肽可能进入吸收细胞，在细胞内发生水解，释放更多的氨基酸。已知氨基酸和肽的运输存在缺陷……膳食蛋白质中的谷氨酸以及分泌到肠道中的内源性蛋白质被消化成自由的氨基酸和小肽，这些都被吸收进入粘膜细胞，其中肽被水解成自由的氨基酸，部分谷氨酸被代谢。过量的谷氨酸和其他氨基酸出现在门脉血液中。由于肠道粘膜细胞和肝脏中谷氨酸的快速代谢，即使摄入大量膳食蛋白质后，系统血浆水平仍然较低。/谷氨酸/

Glutamate is absorbed from the gut by an active transport system specific for amino acids. This process is saturable, can be competitively inhibited, and is dependent on sodium ion concentration... . During intestinal absorption, a large proportion of glutamic acid is transaminated and consequently alanine levels in portal blood are elevated. If large amounts of glutamate are ingested, portal glutamate levels increase ... . This elevation results in increased hepatic metabolism of glutamate, leading to release of glucose, lactate, glutamine, and other amino acids, into systemic circulation ... . The pharmacokinetics of glutamate depend on whether it is free or incorporated into protein, and on the presence of other food components. Digestion of protein in the intestinal lumen and a