关键词: Antioxidants Defence mechanism LMW thiols Oxidative stress Thiol transferases

Mesh : Sulfhydryl Compounds / metabolism Antioxidants / metabolism Transferases / metabolism Oxidation-Reduction Glutathione / metabolism Oxidoreductases / metabolism Disulfides / chemistry

来  源:   DOI:10.1016/j.redox.2024.103094   PDF(Pubmed)

Abstract:
Low-molecular-weight (LMW) thiols are produced in all living cells in different forms and concentrations. Glutathione (GSH), coenzyme A (CoA), bacillithiol (BSH), mycothiol (MSH), ergothioneine (ET) and trypanothione T(SH)2 are the main LMW thiols in eukaryotes and prokaryotes. LMW thiols serve as electron donors for thiol-dependent enzymes in redox-mediated metabolic and signaling processes, protect cellular macromolecules from oxidative and xenobiotic stress, and participate in the reduction of oxidative modifications. The level and function of LMW thiols, their oxidized disulfides and mixed disulfide conjugates in cells and tissues is tightly controlled by dedicated oxidoreductases, such as peroxiredoxins, glutaredoxins, disulfide reductases and LMW thiol transferases. This review provides the first summary of the current knowledge of structural and functional diversity of transferases for LMW thiols, including GSH, BSH, MSH and T(SH)2. Their role in maintaining redox homeostasis in single-cell and multicellular organisms is discussed, focusing in particular on the conjugation of specific thiols to exogenous and endogenous electrophiles, or oxidized protein substrates. Advances in the development of new research tools, analytical methodologies, and genetic models for the analysis of known LMW thiol transferases will expand our knowledge and understanding of their function in cell growth and survival under oxidative stress, nutrient deprivation, and during the detoxification of xenobiotics and harmful metabolites. The antioxidant function of CoA has been recently discovered and the breakthrough in defining the identity and functional characteristics of CoA S-transferase(s) is soon expected.
摘要:
低分子量(LMW)硫醇在所有活细胞中以不同的形式和浓度产生。谷胱甘肽(GSH),辅酶A(CoA),杆菌酯醇(BSH),真菌硫醇(MSH),麦角硫因(ET)和锥替酮T(SH)2是真核生物和原核生物中主要的LMW硫醇。LMW硫醇在氧化还原介导的代谢和信号过程中作为硫醇依赖性酶的电子供体,保护细胞大分子免受氧化和外源性应激,并参与氧化修饰的还原。LMW硫醇的水平和功能,它们在细胞和组织中的氧化二硫化物和混合二硫化物缀合物受到专用氧化还原酶的严格控制,比如过氧化物酶,谷氧还蛋白,二硫化物还原酶和LMW硫醇转移酶。这篇综述提供了LMW硫醇转移酶结构和功能多样性的最新知识的第一个摘要,包括GSH,BSH,MSH和T(SH)2。讨论了它们在维持单细胞和多细胞生物体的氧化还原稳态中的作用,特别关注特定硫醇与外源和内源亲电试剂的缀合,或氧化的蛋白质底物。在开发新的研究工具方面取得的进展,分析方法,和遗传模型分析已知的LMW硫醇转移酶将扩大我们的知识和理解它们在细胞生长和氧化应激下生存的功能,营养剥夺,以及在外源性物质和有害代谢物的解毒过程中。最近已经发现了CoA的抗氧化功能,并且很快预期在定义CoAS-转移酶的身份和功能特征方面的突破。
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