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One-Carbon Metabolism in Health and Disease

机译:健康与疾病中的一种碳代谢

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摘要

One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized. Here we review the fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states. Emphasis is given to recent discoveries enabled by modern genetics, analytical chemistry, and isotope tracing. An emerging theme is the biological importance of mitochondrial 1C reactions, both for producing 1C units that are exported to the cytosol and for making additional products, including glycine and NADPH. Increased clarity regarding differential folate pathway usage in cancer, stem cells, development, and adult physiology is reviewed and highlights new opportunities for selective therapeutic intervention.
机译:由叶酸辅因子介导的单碳(1C)代谢支持多种生理过程。这些包括生物合成(嘌呤和胸苷),氨基酸稳态(甘氨酸,丝氨酸和蛋氨酸),表观遗传维持和氧化还原防御。在真核细胞和跨越器官内,分别为1C代谢反应。在这里,我们审查了哺乳动物1C代谢的基本原理,包括在不同隔间,细胞类型和生物国家中活跃的途径。强调最近发现现代遗传学,分析化学和同位素跟踪的发现。新兴主题是线粒体1C反应的生物重要性,用于生产出口到胞浆溶胶的1C单元,并用于制备额外产品,包括甘氨酸和NADPH。综述了关于癌症,干细胞,发育和成人生理学中的差异叶酸途径使用的清晰度,并突出了选择性治疗干预的新机会。

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