Glutathione metabolism and its implications for health
Glutathione metabolism and its implications for health
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DOI：
10.1093/jn/134.10.2783s
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发表时间：
2004-03-01
影响因子：
4.2
通讯作者：
Turner, ND
中科院分区：
文献类型：
--
作者：
Wu, GY;Fang, YZ;Turner, ND
谷氨酰胺（γ-谷氨酰-半胱氨酰-甘氨酸; GSH）是最丰富的低分子量硫醇，并且GSH/谷胱甘肽二硫化物是动物细胞中的主要氧化还原对。由谷氨酸、半胱氨酸和甘氨酸合成GSH依次由两种胞质酶γ-谷氨酰半胱氨酸合成酶和GSH合成酶催化。令人信服的证据表明，GSH的合成主要是由γ-谷氨酰半胱氨酸合成酶活性，半胱氨酸的可用性，和GSH反馈抑制调节。动物和人类研究表明，充足的蛋白质营养对维持GSH稳态至关重要。此外，肠内或胃肠外胱氨酸、甲硫氨酸、N-乙酰半胱氨酸和L-2-氧代噻唑烷-4-羧酸盐是组织GSH合成的有效半胱氨酸前体。谷氨酸在抗氧化防御、营养代谢和细胞事件（包括基因表达、DNA和蛋白质合成、细胞增殖和凋亡、信号转导、细胞因子产生和免疫应答以及蛋白质谷胱甘肽化）的调节中起重要作用。谷氨酸缺乏导致氧化应激，氧化应激在衰老和许多疾病（包括恶性营养不良、癫痫、阿尔茨海默病、帕金森病、肝病、囊性纤维化、镰状细胞性贫血、HIV、AIDS、癌症、心脏病发作、中风和糖尿病）的发病机制中起关键作用。谷胱甘肽代谢的营养调节的新知识是至关重要的发展有效的战略，以改善健康和治疗这些疾病。
Glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) is the most abundant low-molecular-weight thiol, and GSH/glutathione disulfide is the major redox couple in animal cells. The synthesis of GSH from glutamate, cysteine, and glycine is catalyzed sequentially by two cytosolic enzymes,,gamma-glutamylcysteine synthetase and GSH synthetase. Compelling evidence shows that GSH synthesis is regulated primarily by gamma-glutamylcysteine synthetase activity, cysteine availability, and GSH feedback inhibition. Animal and human studies demonstrate that adequate protein nutrition is crucial for the maintenance of GSH homeostasis. In addition, enteral or parenteral cystine, methionine, N-acetyl-cysteine, and L-2-oxothiazolidine-4-carboxylate are effective precursors of cysteine for tissue GSH synthesis. Glutathione plays important roles in antioxidant defense, nutrient metabolism, and regulation of cellular events (including gene expression, DNA and protein synthesis, cell proliferation and apoptosis, signal transduction, cytokine production and immune response, and protein glutathionylation). Glutathione deficiency contributes to oxidative stress, which plays a key role in aging and the pathogenesis of many diseases (including kwashiorkor, seizure, Alzheimer's disease, Parkinson's disease, liver disease, cystic fibrosis, sickle cell anemia, HIV, AIDS, cancer, heart attack, stroke, and diabetes). New knowledge of the nutritional regulation of GSH metabolism is critical for the development of effective strategies to improve health and to treat these diseases.