健康与疾病中的一碳代谢
One-Carbon Metabolism in Health and Disease.
作者信息
Ducker Gregory S, Rabinowitz Joshua D
机构信息
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
出版信息
Cell Metab. 2017 Jan 10;25(1):27-42. doi: 10.1016/j.cmet.2016.08.009. Epub 2016 Sep 15.
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.
由叶酸辅因子介导的一碳（1C）代谢支持多种生理过程。这些过程包括生物合成（嘌呤和胸苷）、氨基酸稳态（甘氨酸、丝氨酸和甲硫氨酸）、表观遗传维持和氧化还原防御。在真核细胞内以及跨器官过程中，1C代谢反应都是 compartmentalized 的。在这里，我们综述了哺乳动物1C代谢的基本原理，包括在不同区室、细胞类型和生物学状态下活跃的途径。重点介绍了现代遗传学、分析化学和同位素示踪所带来的最新发现。一个新出现的主题是线粒体1C反应的生物学重要性，这不仅体现在产生输出到细胞质的1C单位，还体现在制造包括甘氨酸和NADPH在内的其他产物。本文综述了在癌症、干细胞、发育和成年生理学中叶酸途径差异使用的更清晰认识，并强调了选择性治疗干预的新机会。 （注：compartmentalized 这个词在文中似乎有误，可能是compartmentalized，意思是“分隔的” ）
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