谷胱甘肽
谷胱甘肽(英语:Glutathione,简称:GSH),又称麸胱甘肽或麸氨基硫,[1]属于三肽,由谷氨酸、半胱氨酸及甘氨酸所构成,其中第一个肽键与普通的肽键不同,是由谷氨酸的γ-羧基与半胱氨酸的氨基组成的,在分子中半胱氨酸巯基是该化合物的主要功能基团。谷胱甘肽是植物、动物、真菌和一些细菌和古菌中的一种抗氧化剂。谷胱甘肽能够防止活性氧、自由基、过氧化物、脂质过氧化物和重金属等来源对重要细胞成分造成的损害。[2] 作为动物细胞中的抗氧化剂,存在于充满水的细胞内部,可以保护DNA免于氧化。谷胱甘肽以两种型态存在于人体,一是还原型态、另一是氧化型态。菠菜含有谷胱甘肽。
谷胱甘肽 | |
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IUPAC名 γ-Glutamylcysteinylglycine | |
别名 | γ-L-Glutamyl-L-cysteinylglycine (2S)-2-Amino-4-({(1R)-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl}carbamoyl)butanoic acid |
缩写 | GSH |
识别 | |
CAS号 | 70-18-8 |
PubChem | 124886 |
ChemSpider | 111188 |
SMILES |
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ChEBI | 16856 |
DrugBank | DB00143 |
KEGG | C00051 |
MeSH | Glutathione |
性质 | |
化学式 | C10H17N3O6S |
摩尔质量 | 307.325 g·mol⁻¹ |
熔点 | 195[1] |
溶解性(水) | 易溶[1] |
溶解性(甲醇, 乙醚) | 不溶[1] |
药理学 | |
ATC代码 | V03AB32(V03) |
若非注明,所有数据均出自标准状态(25 ℃,100 kPa)下。 |
生物合成和储存
编辑谷胱甘肽生物合成涉及两个三磷酸腺苷依赖的步骤:
- 首先,γ-谷氨酰半胱氨酸由 L-谷氨酸和 L-半胱氨酸合成。此转化需要酶谷氨酸-半胱氨酸连接酶 (GCL,谷氨酸半胱氨酸合酶)。此反应是谷胱甘肽合成中的限速步骤。[3]
- 其次,将甘氨酸添加到γ-谷氨酰半胱氨酸的C末端。该缩合反应由谷胱甘肽合成酶催化。
虽然所有动物细胞都能够合成谷胱甘肽,但已证明肝脏中的谷胱甘肽合成至关重要。GCLC基因敲除小鼠由于缺乏肝脏GSH合成而在出生后一个月内死亡。[4][5] 谷胱甘肽中不寻常的γ酰胺键保护它免受肽酶的水解。[6]
储存
编辑谷胱甘肽是动物细胞中最丰富的非蛋白硫醇(含 R-SH 的化合物),含量范围为 0.5 至 10 mmol/L。它存在于细胞质和细胞器中。在健康细胞和组织中,[6]总谷胱甘肽池的 90% 以上为还原形式(GSH),其余为二硫化物氧化形式(GSSG)。[7]80-85% 的细胞GSH存在于细胞质中,10-15% 存在于线粒体中。[8]
人体能够合成谷胱甘肽,但少数真核生物不会合成谷胱甘肽,包括豆科植物、内阿米巴属和贾第鞭毛虫属的部分成员。已知唯一能合成谷胱甘肽的古细菌是盐杆菌纲。某些细菌,如“蓝藻”和假单胞菌,可以生物合成谷胱甘肽。[9][10]
口服谷胱甘肽的全身利用度生物利用度较差,因为三肽是消化道蛋白酶(肽酶)的底物,并且由于细胞膜水平上缺乏谷胱甘肽的特定载体。[11][12]服用半胱氨酸前体药物 N-乙酰半胱氨酸 (NAC) 有助于补充细胞内 GSH 水平。[13]专利化合物 RiboCeine 已被研究作为一种补充剂,可增强谷胱甘肽的产生,从而有助于缓解高血糖。[14][15]
生物学功能
编辑谷胱甘肽以还原(GSH)和氧化(GSSG)状态存在。[16]细胞内还原谷胱甘肽与氧化谷胱甘肽的比率是细胞氧化应激的量度,[17][8]其中 GSSG 与 GSH 比率增加表明氧化应激更大。
在还原状态下,半胱氨酰残基的硫醇基团是一个还原当量的来源。由此生成谷胱甘肽二硫化物 (GSSG)的氧化状态通过NADPH[18]转化为还原状态(GSH)。该转化由谷胱甘肽还原酶催化
作用
编辑抗氧化剂
编辑GSH通过中和(减少)活性氧来保护细胞。[19][6]这种转化可以通过过氧化物的还原来说明:
- 2 GSH + R2O2 → GSSG + 2 ROH (R = 氢,烷基 )
以及自由基:
- GSH + R• → 1/2 GSSG + RH
调节
编辑除了使自由基和活性氧化剂失活外,谷胱甘肽还参与硫醇保护和氧化应激下细胞硫醇蛋白的氧化还原调节,通过蛋白质“S”-谷胱甘肽化,一种氧化还原调节的翻译后硫醇修饰。一般反应涉及从可保护蛋白质 (RSH) 和 GSH 形成不对称二硫化物:[20]
- RSH + GSH + [O] → GSSR + H2O
谷胱甘肽还用于解毒氧化应激产生的有毒代谢物甲基乙二醛和甲醛。该解毒反应由乙二醛酶系统进行。乙二醛酶I (EC 4.4.1.5) 催化甲基乙二醛和还原谷胱甘肽转化为 S-D-乳酰谷胱甘肽。乙二醛酶II (EC 3.1.2.6) 催化 S-D-乳酰谷胱甘肽水解为谷胱甘肽和D-乳酸。
它维持外源性抗氧化剂如维生素C和维生素E处于还原(活性)状态。[21][22][23]
新陈代谢
编辑在其参与的众多代谢过程中,谷胱甘肽是白三烯和前列腺素生物合成所必需的。它在半胱氨酸的储存中发挥作用。谷胱甘肽增强了瓜氨酸作为一氧化氮循环一部分的功能。[24]它是一种辅因子并作用于谷胱甘肽过氧化物酶。[25] 谷胱甘肽用于生成 S-硫烷基谷胱甘肽,它是硫化氢代谢的一部分。[26]
结合
编辑谷胱甘肽促进外来化合物代谢。谷胱甘肽S-转移酶催化其与亲脂性外来化合物结合,促进其排泄或进一步代谢。[27]结合过程以N-乙酰基-p-苯醌亚胺(NAPQI) 的代谢为例。NAPQI 是一种活性代谢物,由细胞色素 P450作用于对乙酰氨基酚(乙酰氨基酚) 而形成。谷胱甘肽与 NAPQI 结合,并将所得复合物排出体外。
在植物中
编辑在植物中,谷胱甘肽参与活性氧压力管理。它是谷胱甘肽-抗坏血酸循环的组成部分,该系统可减少有毒的过氧化氢。[28] 它是植物螯合素、谷胱甘肽低聚物的前体,可以螯合镉等重金属。[29]谷胱甘肽是有效防御植物病原体(例如“丁香假单胞菌”和“芸苔疫霉菌”)所必需的。[30]腺苷酸硫酸还原酶是硫同化途径的一种酶,它使用谷胱甘肽作为电子供体。其他使用谷胱甘肽作为底物的酶是谷氧还蛋白。这些小的氧化还原酶参与了花的发育、水杨酸和植物防御信号传导。[31]
用途
编辑酿酒
编辑葡萄酒的第一个原料形式葡萄浆中的谷胱甘肽含量决定了白葡萄酒生产过程中的褐变或焦糖化效果,因为它可以捕获酶氧化产生的咖啡酰酒石酸醌作为葡萄反应产物。[32]可以通过UPLC-MRM质谱法测定葡萄酒中的该物质的浓度。[33]
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