The Incomplete Glutathione Puzzle: Just Guessing at Numbers and Figures?
The Incomplete Glutathione Puzzle: Just Guessing at Numbers and Figures?
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DOI：
10.1089/ars.2017.7123
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发表时间：
2017-11-20
影响因子：
6.6
通讯作者：
Deponte M
中科院分区：
文献类型：
--
作者：
Deponte M
意义：糖代谢就像一个有太多碎片的拼图。它应该包括（i）二硫化物，氢过氧化物，次磺酸和亚硝基硫醇的还原，（ii）醛，异生物质和重金属的解毒，以及（iii）类花生酸，类固醇和铁硫簇的合成。此外，谷胱甘肽影响氧化蛋白质折叠和氧化还原信号。在这里，我试图提供一个概述谷胱甘肽依赖途径的相关性，重点是定量数据。最新进展：细胞内氧化还原测量表明，细胞质，细胞核和线粒体含有非常少的谷胱甘肽二硫化物和氧化的挑战迅速平衡。遗传学方法表明，铁代谢是酵母谷胱甘肽之谜的核心。此外，最近的生化研究提供了新的见解谷胱甘肽转运过程和解偶联机制。关键问题：谷胱甘肽之谜的哪些部分最相关？这是否解释了细胞内还原型谷胱甘肽的高浓度？在高谷胱甘肽浓度下，铁硫簇生物合成、氧化蛋白质折叠或氧化还原信号是如何发生的？这些问题的答案似乎不仅取决于生物体，细胞类型和亚细胞区室，而且还取决于研究人员之间的不同意识形态。未来方向：比较谷胱甘肽依赖途径相关性的一个合理方法是将联合收割机遗传学和定量动力学数据结合起来。然而，仍然有许多缺失的部分，并且对许多代谢物、底物、酶和转运蛋白的隔室特异性库和浓度以及速率常数和酶动力学模式知之甚少。收集这些信息可能需要开发新的工具，但对于解决潜在的动力学竞争和破译解偶联机制以解决谷胱甘肽之谜至关重要。抗氧化剂。氧化还原信号。27，1130-1161。
Significance: Glutathione metabolism is comparable to a jigsaw puzzle with too many pieces. It is supposed to comprise (i) the reduction of disulfides, hydroperoxides, sulfenic acids, and nitrosothiols, (ii) the detoxification of aldehydes, xenobiotics, and heavy metals, and (iii) the synthesis of eicosanoids, steroids, and iron–sulfur clusters. In addition, glutathione affects oxidative protein folding and redox signaling. Here, I try to provide an overview on the relevance of glutathione-dependent pathways with an emphasis on quantitative data. Recent Advances: Intracellular redox measurements reveal that the cytosol, the nucleus, and mitochondria contain very little glutathione disulfide and that oxidative challenges are rapidly counterbalanced. Genetic approaches suggest that iron metabolism is the centerpiece of the glutathione puzzle in yeast. Furthermore, recent biochemical studies provide novel insights on glutathione transport processes and uncoupling mechanisms. Critical Issues: Which parts of the glutathione puzzle are most relevant? Does this explain the high intracellular concentrations of reduced glutathione? How can iron–sulfur cluster biogenesis, oxidative protein folding, or redox signaling occur at high glutathione concentrations? Answers to these questions not only seem to depend on the organism, cell type, and subcellular compartment but also on different ideologies among researchers. Future Directions: A rational approach to compare the relevance of glutathione-dependent pathways is to combine genetic and quantitative kinetic data. However, there are still many missing pieces and too little is known about the compartment-specific repertoire and concentration of numerous metabolites, substrates, enzymes, and transporters as well as rate constants and enzyme kinetic patterns. Gathering this information might require the development of novel tools but is crucial to address potential kinetic competitions and to decipher uncoupling mechanisms to solve the glutathione puzzle. Antioxid. Redox Signal. 27, 1130–1161.
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影响因子：
16.6
作者：
Begas P;Liedgens L;Moseler A;Meyer AJ;Deponte M
通讯作者：
Deponte M
影响因子：
4.8
作者：
Bito, A;Haider, M;Breitenbach, M
通讯作者：
Breitenbach, M
DOI：
10.1073/pnas.87.19.7782
发表时间：
1990-10-01
影响因子：
11.1
作者：
AMES, BN;PROFET, M;GOLD, LS
通讯作者：
GOLD, LS
影响因子：
11.4
作者：
Bandyopadhyay, Sibali;Gama, Filipe;Rouhier, Nicolas
通讯作者：
Rouhier, Nicolas
影响因子：
4.8
作者：
Avval, Farnaz Zahedi;Holmgren, Arne
通讯作者：
Holmgren, Arne