Pócsi István, Prade Rolf A, Penninckx Michel J
Department of Microbiology and Biotechnology, Faculty of Sciences, University of Debrecen, P.O. Box 63, H-4010 Debrecen, Hungary.
Adv Microb Physiol. 2004;49:1-76. doi: 10.1016/S0065-2911(04)49001-8.
Glutathione (GSH; gamma-L-glutamyl-L-cysteinyl-glycine), a non-protein thiol with a very low redox potential (E'0 = 240 mV for thiol-disulfide exchange), is present in high concentration up to 10 mM in yeasts and filamentous fungi. GSH is concerned with basic cellular functions as well as the maintenance of mitochondrial structure, membrane integrity, and in cell differentiation and development. GSH plays key roles in the response to several stress situations in fungi. For example, GSH is an important antioxidant molecule, which reacts non-enzymatically with a series of reactive oxygen species. In addition, the response to oxidative stress also involves GSH biosynthesis enzymes, NADPH-dependent GSH-regenerating reductase, glutathione S-transferase along with peroxide-eliminating glutathione peroxidase and glutaredoxins. Some components of the GSH-dependent antioxidative defence system confer resistance against heat shock and osmotic stress. Formation of protein-SSG mixed disulfides results in protection against desiccation-induced oxidative injuries in lichens. Intracellular GSH and GSH-derived phytochelatins hinder the progression of heavy metal-initiated cell injuries by chelating and sequestering the metal ions themselves and/or by eliminating reactive oxygen species. In fungi, GSH is mobilized to ensure cellular maintenance under sulfur or nitrogen starvation. Moreover, adaptation to carbon deprivation stress results in an increased tolerance to oxidative stress, which involves the induction of GSH-dependent elements of the antioxidant defence system. GSH-dependent detoxification processes concern the elimination of toxic endogenous metabolites, such as excess formaldehyde produced during the growth of the methylotrophic yeasts, by formaldehyde dehydrogenase and methylglyoxal, a by-product of glycolysis, by the glyoxalase pathway. Detoxification of xenobiotics, such as halogenated aromatic and alkylating agents, relies on glutathione S-transferases. In yeast, these enzymes may participate in the elimination of toxic intermediates that accumulate in stationary phase and/or act in a similar fashion as heat shock proteins. GSH S-conjugates may also form in a glutathione S-transferases-independent way, e.g. through chemical reaction between GSH and the antifugal agent Thiram. GSH-dependent detoxification of penicillin side-chain precursors was shown in Penicillium sp. GSH controls aging and autolysis in several fungal species, and possesses an anti-apoptotic feature.
谷胱甘肽（GSH；γ-L-谷氨酰-L-半胱氨酰甘氨酸）是一种氧化还原电位极低（硫醇-二硫键交换的E'0 = 240 mV）的非蛋白质硫醇，在酵母和丝状真菌中以高达10 mM的高浓度存在。谷胱甘肽与基本细胞功能以及线粒体结构的维持、膜完整性以及细胞分化和发育有关。谷胱甘肽在真菌对几种应激情况的反应中起关键作用。例如，谷胱甘肽是一种重要的抗氧化分子，它与一系列活性氧发生非酶反应。此外，对氧化应激的反应还涉及谷胱甘肽生物合成酶、NADPH依赖性谷胱甘肽再生还原酶、谷胱甘肽S-转移酶以及消除过氧化物的谷胱甘肽过氧化物酶和谷氧还蛋白。谷胱甘肽依赖性抗氧化防御系统的一些成分赋予对热休克和渗透胁迫的抗性。蛋白质-SSG混合二硫键的形成可保护地衣免受干燥诱导的氧化损伤。细胞内谷胱甘肽和谷胱甘肽衍生的植物螯合肽通过螯合和隔离金属离子本身和/或通过消除活性氧来阻碍重金属引发的细胞损伤的进展。在真菌中，谷胱甘肽被调动起来以确保在硫或氮饥饿条件下的细胞维持。此外，对碳剥夺胁迫的适应导致对氧化应激的耐受性增加，这涉及诱导抗氧化防御系统中依赖谷胱甘肽的元件。谷胱甘肽依赖性解毒过程涉及消除有毒的内源性代谢物，例如甲基营养型酵母生长过程中产生的过量甲醛，通过甲醛脱氢酶，以及乙二醛，糖酵解的副产物，通过乙二醛酶途径。对外源化合物，如卤代芳烃和烷基化剂的解毒依赖于谷胱甘肽S-转移酶。在酵母中，这些酶可能参与消除在稳定期积累的有毒中间体和/或以与热休克蛋白类似的方式起作用。谷胱甘肽S-共轭物也可能以不依赖谷胱甘肽S-转移酶的方式形成，例如通过谷胱甘肽与抗真菌剂福美双之间的化学反应。在青霉属中显示了谷胱甘肽依赖性对青霉素侧链前体的解毒作用。谷胱甘肽控制几种真菌物种的衰老和自溶，并具有抗凋亡特性。
