Inhibition of mammalian thymidylate synthase by 10-formyltetrahydropteroylpolyglutamate.
Inhibition of mammalian thymidylate synthase by 10-formyltetrahydropteroylpolyglutamate.
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10-甲酰四氢蝶酰聚谷氨酸对哺乳动物胸苷酸合酶的抑制作用。
DOI：
10.1016/0003-9861(91)90287-s
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发表时间：
1991
影响因子：
3.9
通讯作者：
Galivan,J
中科院分区：
文献类型：
--
作者：
Balinska,M;Rhee,M;Whiteley,JM;Priest,DG;Galivan,J
10-甲酰叶酸的还原衍生物已被评估为 H35 肝癌细胞的哺乳动物胸苷酸合酶 (EC 2.1.1.45) 的抑制剂。以5,10-亚甲基四氢叶酰七谷氨酸为底物，10-甲酰四氢叶酰单谷氨酸是一种竞争性抑制剂，其尺寸为2.4 μm，对于七谷氨酸衍生物，其尺寸减小至0.1 μm。 10-甲酰二氢叶酰单-和-七谷氨酸的抑制作用比四氢类似物低大约三倍。通过一种新型酶法测定分裂中的肝癌细胞中 10-甲酰四氢叶酸和 10-甲酰二氢叶酸的浓度，结果分别为 5 μ 和不可检测。这些结果表明，分裂细胞内 10-甲酰四氢叶酸的浓度有可能严重抑制或调节胸苷酸生物合成。
Reduced derivatives of 10-formylfolate have been evaluated as inhibitors of mammalian thymidylate synthase (EC 2.1.1.45) from H35 hepatoma cells. With 5,10-methylenetetrahydrofolylheptaglutamate as the substrate, 10-formyltetrahydrofolylmonoglutamate is a competitive inhibitor with akiof 2.4 μm, which is reduced to 0.1 μmfor the heptaglutamate derivative. 10-Formyldihydrofolylmono- and -heptaglutamate are approximately threefold less inhibitory than the tetrahydro analog. The concentrations of 10-formyltetrahydrofolate and 10-formyldihydrofolate were measured in dividing hepatoma cells by a novel enzymatic assay and were found to be 5 μmand undetectable, respectively. These results suggest that the concentration of 10-formyltetrahydrofolate within the dividing cells has the potential to severely inhibit or modulate thymidylate biosynthesis.