One-carbon metabolism

This one-carbon metabolism pathway is centered around folate. Folate has two key carbon-carbon double bonds. Saturating one of them yields dihydrofolate (DHF) and adding an additional molecule of hydrogen across the second yields tetrahydrofolate (THF). Folates serve as donors of single carbons in any one of three oxidation states: 5-methyl-THF (CH3THF; reduced), 5,10 methylene-THF (CH2THF; intermediate) and 10-formyl-THF (CHOTHF; oxidized). The single carbon donor CH3THF is used to convert homocysteine into methionine which can then be used to methylate DNA, the donor CH2THF is used (along with a molecule of hydrogen at the site of one of the double bonds) to convert dUMP (deoxyuridylate) into dTMP (thymidylate) and the donor CHOTHF is used to set up ring closure reactions in de novo purine synthesis. CH3THF is the primary methyl-group donor for processes such as DNA methylation reactions. Purines are used both in RNA synthesis and in DNA synthesis and dTMP is synthesized srtictly for DNA synthesis, be it for DNA repair or DNA replication. The folate pathway is central to any study related to DNA methylation, dTMP synthesis or purine synthesis. Differential methylation (e.g. hypermethylation of tumor suppressors) as well as disturbances in nucleotide synthesis and repair, are associated with several forms of cancer. There are also indications that hypermethylation is involved in the progression of adenomas to cancer. The pathway is also illustrative of the role of a number of B vitamins, including vitamin B12 (cobalamine) which is important for the sythesis of folate (vitamin B9) and of methionine. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP241 CPTAC Assay Portal]

此一碳代谢途径以叶酸为核心。叶酸包含两个关键的碳-碳双键。饱和其中一个双键生成二氢叶酸（DHF），而在第二个双键上添加一个氢分子则生成四氢叶酸（THF）。叶酸可作为单一碳的供体，存在于三种氧化态之一：5-甲基-THF（CH3THF；还原态）、5,10-亚甲基-THF（CH2THF；中间态）和10-甲酰-THF（CHOTHF；氧化态）。单一碳供体CH3THF用于将同型半胱氨酸转化为甲硫氨酸，甲硫氨酸随后可用于甲基化DNA；供体CH2THF（以及一个氢分子，位于其中一个双键的位置）用于将脱氧尿苷酸（dUMP）转化为胸苷酸（dTMP）；供体CHOTHF用于在新嘌呤合成中的环闭合反应。CH3THF是DNA甲基化反应等过程中的主要甲基供体。嘌呤在RNA合成和DNA合成中均有应用，而dTMP的合成则严格用于DNA合成，无论是DNA修复还是DNA复制。叶酸途径是任何与DNA甲基化、dTMP合成或嘌呤合成相关研究的核心。差异甲基化（例如肿瘤抑制基因的高甲基化）以及核苷酸合成和修复的紊乱，与多种癌症形式相关。也有迹象表明，高甲基化与腺瘤向癌症的进展有关。该途径亦揭示了多种B族维生素（包括维生素B12（钴胺素））的作用，维生素B12对叶酸（维生素B9）和甲硫氨酸的合成至关重要。该途径上的蛋白质可通过[https://assays.cancer.gov/available_assays?wp_id=WP241 CPTAC检测门户]进行针对性的检测。