Glutathione synthesis.
Glutathione synthesis.
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DOI：
10.1016/j.bbagen.2012.09.008
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发表时间：
2013-05
影响因子：
3
通讯作者：
Lu, Shelly C.
中科院分区：
文献类型：
--
作者：
Lu, Shelly C.
谷胱甘肽(GSH)作为最丰富的非蛋白硫醇存在于所有哺乳动物组织中，可抵御氧化应激。GSH也是氧化还原信号的关键决定因素，在外源物质的解毒中至关重要，调节细胞增殖、凋亡、免疫功能和纤维化形成。GSH的生物合成在细胞质中以严格调控的方式进行。GSH合成的关键决定因素是含硫氨基酸前体半胱氨酸的可用性和限速酶谷氨酸半胱氨酸连接酶(GCL)的活性，谷氨酸半胱氨酸连接酶(GCL)由催化(GCLC)和修饰物(GCLM)亚基组成。GSH合成的第二个酶是GSH合成酶(GS)。本文综述了GSH的主要功能，并着重介绍了调节GSH生物合成的因素，包括GSH合成失调的病理条件。GCL亚基和GS在多个水平上受到调控，而且往往是以协调的方式进行的。调节这些基因表达的关键转录因子包括通过抗氧化反应元件(ARE)调节的核因子-E2相关因子2(NRF2)、AP-1和核因子-kappaB(NFκB)。越来越多的证据表明，谷胱甘肽合成失调参与了许多病理疾病的发病机制。这些疾病包括糖尿病、肺和肝纤维化、酒精性肝病、淤胆性肝损伤、内毒素血症和耐药肿瘤细胞。GSH是一种关键的抗氧化剂，也可以调节不同的细胞过程。更好地了解它的合成是如何在疾病状态下被调节和失调的，可能会导致这些疾病的治疗方法的改进。
Glutathione (GSH) is present in all mammalian tissues as the most abundant non-protein thiol that defends against oxidative stress. GSH is also a key determinant of redox signaling, vital in detoxification of xenobiotics, regulates cell proliferation, apoptosis, immune function, and fibrogenesis. Biosynthesis of GSH occurs in the cytosol in a tightly regulated manner. Key determinants of GSH synthesis are the availability of the sulfur amino acid precursor, cysteine, and the activity of the rate-limiting enzyme, glutamate cysteine ligase (GCL), which is composed of a catalytic (GCLC) and a modifier (GCLM) subunit. The second enzyme of GSH synthesis is GSH synthetase (GS). This review summarizes key functions of GSH and focuses on factors that regulate the biosynthesis of GSH, including pathological conditions where GSH synthesis is dysregulated. GCL subunits and GS are regulated at multiple levels and often in a coordinated manner. Key transcription factors that regulate the expression of these genes include NF-E2 related factor 2 (Nrf2) via the antioxidant response element (ARE), AP-1, and nuclear factor kappa B (NFκB). There is increasing evidence that dysregulation of GSH synthesis contributes to the pathogenesis of many pathological conditions. These include diabetes mellitus, pulmonary and liver fibrosis, alcoholic liver disease, cholestatic liver injury, endotoxemia and drug-resistant tumor cells. GSH is a key antioxidant that also modulates diverse cellular processes. A better understanding of how its synthesis is regulated and dysregulated in disease states may lead to improvement in the treatment of these disorders.
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影响因子：
5.5
作者：
Cortese-Krott, Miriam M.;Suschek, Christoph V.;Kolb-Bachofen, Victoria
通讯作者：
Kolb-Bachofen, Victoria
影响因子：
4.1
作者：
Cai, JX;Huang, ZZ;Lu, SC
通讯作者：
Lu, SC
影响因子：
4
作者：
Carretero, J;Obrador, E;Estrela, JM
通讯作者：
Estrela, JM
影响因子：
10.6
作者：
Forman, Henry Jay;Zhang, Hongqiao;Rinna, Alessandra
通讯作者：
Rinna, Alessandra
DOI：
10.1016/s0167-4781(00)00238-4
发表时间：
2000-12-15
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Chan, JY;Kwong, M
通讯作者：
Kwong, M