MTHFD1L transforms 10-formyl-THF to HCOOH and THF

All C1-tetrahydrofolate (C1-THF) synthases characterised to date are trifunctional, containing the activities of 5,10-methylene-THF dehydrogenase, 5,10-methenyl-THF cyclohydrolase, and 10-formyl-THF synthetase. Mitochondrial monofunctional C1-tetrahydrofolate synthase (MTHFD1L) only possesses 10-formyl-THF synthetase activity and it reversibly ligates formate (HCOOH) to tetrahydrofolate (THF), forming 10-formyltetrahydrofolate (10-formyl-THF) (Prasannan et al. 2003, Walkup & Appling 2005). MTHFD1L is functional as a homodimer and could be a missing reaction in one-carbon folate metabolism linking the metabolism of formate from the cytosol to mitochondria (Pike et al. 2010). Under most conditions, the majority of one-carbon units for cytoplasmic processes are derived from mitochondrial formate.

截至目前，所有已表征的C1-四氢叶酸合酶均为多功能酶，其活性包括5,10-亚甲基四氢叶酸脱氢酶、5,10-亚甲基四氢叶酸环合酶以及10-甲酰四氢叶酸合成酶。线粒体单功能C1-四氢叶酸合酶（MTHFD1L）仅具有10-甲酰四氢叶酸合成酶活性，并能可逆地将甲酸（HCOOH）与四氢叶酸（THF）结合，形成10-甲酰四氢叶酸（10-formyl-THF）（Prasannan等，2003，Walkup & Appling，2005）。MTHFD1L作为同源二聚体具有功能，可能是连接细胞质中甲酸代谢与线粒体代谢的一个缺失反应，该反应涉及一碳单位在四氢叶酸代谢中的作用（Pike等，2010）。在大多数情况下，细胞质中用于代谢过程的一碳单位主要来源于线粒体的甲酸。