Fox Jennifer T, Stover Patrick J
Graduate Field of Biochemistry, Molecular and Cellular Biology, Cornell University, Ithaca, New York 14853, USA.
Vitam Horm. 2008;79:1-44. doi: 10.1016/S0083-6729(08)00401-9.
Tetrahydrofolate (THF) polyglutamates are a family of cofactors that carry and chemically activate one-carbon units for biosynthesis. THF-mediated one-carbon metabolism is a metabolic network of interdependent biosynthetic pathways that is compartmentalized in the cytoplasm, mitochondria, and nucleus. One-carbon metabolism in the cytoplasm is required for the synthesis of purines and thymidylate and the remethylation of homocysteine to methionine. One-carbon metabolism in the mitochondria is required for the synthesis of formylated methionyl-tRNA; the catabolism of choline, purines, and histidine; and the interconversion of serine and glycine. Mitochondria are also the primary source of one-carbon units for cytoplasmic metabolism. Increasing evidence indicates that folate-dependent de novo thymidylate biosynthesis occurs in the nucleus of certain cell types. Disruption of folate-mediated one-carbon metabolism is associated with many pathologies and developmental anomalies, yet the biochemical mechanisms and causal metabolic pathways responsible for the initiation and/or progression of folate-associated pathologies have yet to be established. This chapter focuses on our current understanding of mammalian folate-mediated one-carbon metabolism, its cellular compartmentation, and knowledge gaps that limit our understanding of one-carbon metabolism and its regulation.
四氢叶酸（THF）多聚谷氨酸是一类辅因子，它们携带并化学活化用于生物合成的一碳单位。THF介导的一碳代谢是一个相互依存的生物合成途径的代谢网络，该网络在细胞质、线粒体和细胞核中进行区室化分布。细胞质中的一碳代谢对于嘌呤和胸苷酸的合成以及同型半胱氨酸再甲基化生成甲硫氨酸是必需的。线粒体中的一碳代谢对于甲酰化甲硫氨酰 - tRNA的合成、胆碱、嘌呤和组氨酸的分解代谢以及丝氨酸和甘氨酸的相互转化是必需的。线粒体也是细胞质代谢中一碳单位的主要来源。越来越多的证据表明，叶酸依赖性的胸苷酸从头生物合成发生在某些细胞类型的细胞核中。叶酸介导的一碳代谢紊乱与许多病理状况和发育异常有关，但导致叶酸相关病理状况起始和/或进展的生化机制和因果代谢途径尚未明确。本章重点阐述我们目前对哺乳动物叶酸介导的一碳代谢、其细胞区室化以及限制我们对一碳代谢及其调控理解的知识空白的认识。
