Matthews R G
Fed Proc. 1982 Jul;41(9):2600-4.
Tetrahydrofolate (H4folate) derivatives are chemically analogous to tetrahydropterins and dihydroflavins, and like these compounds can be oxidized readily. The roles of pterin and flavin cofactors in biological oxidoreductions are well documented. However, with the exception of the reaction catalyzed by thymidylate synthase, explicit oxidoreductions of the H4folate cofactor do not occur in enzyme-catalyzed folate-dependent reactions. We have been studying methylenetetrahydrofolate reductase from pig liver. This enzyme catalyzes the reversible conversion of the exocyclic N5,N10-methylene substituent to an N5-methyl group. Our studies suggest that the detailed mechanism of this reduction of an exocyclic group involves the oxidoreduction of the tetrahydropterin ring system in a manner that is not apparent from the overall reaction stoichiometry. We suggest that such latent oxidoreductions of H4folate cofactors may also occur in other H4folate-dependent reactions, such as the reaction catalyzed by methionine synthase.
四氢叶酸（H4叶酸）衍生物在化学结构上类似于四氢蝶呤和二氢黄素，并且像这些化合物一样容易被氧化。蝶呤和黄素辅因子在生物氧化还原反应中的作用已有充分记载。然而，除了胸苷酸合酶催化的反应外，在酶催化的依赖叶酸的反应中，H4叶酸辅因子并没有明确的氧化还原反应发生。我们一直在研究猪肝中的亚甲基四氢叶酸还原酶。该酶催化环外N5,N10-亚甲基取代基可逆地转化为N5-甲基基团。我们的研究表明，这种环外基团还原的详细机制涉及四氢蝶呤环系统的氧化还原，而这从总体反应化学计量中并不明显。我们认为，这种H4叶酸辅因子的潜在氧化还原反应也可能发生在其他依赖H4叶酸的反应中，例如甲硫氨酸合酶催化的反应。
