Abstract:
Metabolism within an organism is regulated by various processes, including post-translational modifications (PTMs). These types of chemical modifications alter the molecular, biochemical, and cellular properties of proteins and allow the organism to respond quickly to different environments, energy states, and stresses. Malate dehydrogenase (MDH) is a metabolic enzyme that is conserved in all domains of life and is extensively modified post-translationally. Due to the central role of MDH, its modification can alter metabolic flux, including the Krebs cycle, glycolysis, and lipid and amino acid metabolism. Despite the importance of both MDH and its extensively post-translationally modified landscape, comprehensive characterization of MDH PTMs, and their effects on MDH structure, function, and metabolic flux remains underexplored. Here, we review three types of MDH PTMs - acetylation, ADP-ribosylation, and methylation - and explore what is known in the literature and how these PTMs potentially affect the 3D structure, enzymatic activity, and interactome of MDH. Finally, we briefly discuss the potential involvement of PTMs in the dynamics of metabolons that include MDH.
摘要:
生物体内的代谢受各种过程的调节,包括翻译后修饰(PTM)。这些类型的化学修饰改变了分子,生物化学,和蛋白质的细胞特性,并允许生物体对不同的环境做出快速反应,能量状态,和压力。苹果酸脱氢酶(MDH)是一种代谢酶,在生命的所有领域都是保守的,并且在翻译后被广泛修饰。由于MDH的核心作用,它的修饰可以改变代谢通量,包括克雷布斯周期,糖酵解,和脂质和氨基酸代谢。尽管MDH及其广泛的翻译后修改景观的重要性,MDHPTM的综合表征,以及它们对MDH结构的影响,函数,代谢通量仍未充分开发。这里,我们回顾了三种类型的MDHPTM-乙酰化,ADP-核糖基化,和甲基化-并探索文献中已知的内容以及这些PTM如何潜在影响3D结构,酶活性,和MDH的相互作用。最后,我们简要讨论了PTM在包括MDH在内的代谢物动力学中的潜在参与。