INTERACTION OF FORMALDEHYDE AND TETRAHYDROFOLIC ACID AND ITS RELATION TO THE ENZYMIC SYNTHESIS OF SERINE
INTERACTION OF FORMALDEHYDE AND TETRAHYDROFOLIC ACID AND ITS RELATION TO THE ENZYMIC SYNTHESIS OF SERINE
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DOI：
10.1038/1821719a0
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发表时间：
1958-01-01
期刊：
影响因子：
64.8
通讯作者：
BLAKLEY, RL
中科院分区：
文献类型：
--
作者：
BLAKLEY, RL
甘氨酸和甲醛在一种来自肝脏的酶的存在下反应生成丝氨酸需要四氢叶酸(FH，I)作为辅助因子，它被认为是通过与甲醛形成活性络合物而起作用的。1954年，“活性甲醛”的结构首次被假定为N：，N：-亚甲基FH，(Iii)，尽管N：-羟甲基FH，(Ii)也是一种可能的结构“。甲醛与1：2-二胺强烈结合，形成桥联结构。证明N，N‘-二苯乙二胺很容易与甲醛反应生成稳定的环状产物。因此，可以预料的是，FH，也是I：2-二胺，将与甲醛反应生成III，并且该化合物将通过牢固结合的亚甲基桥的存在稳定到氧气中。虽然甲醛与FH反应的产物比FH本身更稳定，但它对氧气非常敏感，因为在水溶液中，当在空气中摇动时，它会迅速失去辅酶活性。这种对氧的敏感性已被分光光度研究所证实。当FH的溶液用磷酸盐缓冲液(pH 7-2)稀释到5×10-*M的浓度时，光谱在几分钟内从FH的光谱(X.298 MP.)对氧化产物的影响。在较短的波长(最终为275MP.)。如果稀释剂含有甲醛，则由于氧化引起的变化率较小，但即使在存在10-×M甲醛的情况下，其变化率也约为不含甲醛时的3%。在这个实验室中，反应混合物的纸色谱没有像其他人报告的那样，产生与FH不同的RP产物的明显分离。这些结果最初被解释为表明II必须是产物的结构，并且它必须容易解离。研究了FH与~(14)C标记的甲醛与氢化蝶呤的结合，结果表明，FH与甲醛结合的分子比例约为FH，N：“-甲酰基FH与甲醛结合的分子比例较少，2-氨基-4-羟基-6-甲基四氢蝶啶与亮氨酸结合的分子比例较少。通过测定甲醛与已知氢化蝶呤的平衡浓度，证实并推广了这些结果。由于四氢蝶啶相当不稳定，四氢喹恶啉与之接近
HE reaction between glycine and formaldehyde to form serine in the presence of an enzyme from liver* requires, as a co-factor, tetrahydrofolic acid (FH, I), which is believed to act by forming a reactive complex with formaldehyde. The structure of the “active formaldehyde” was first postulated as Nº, Nº-methyleneFH,(III) in 1954, although Nºº-hydroxymethylFH,(II) is also a possible structure". Formaldehyde is bound strongly by 1: 2-diamines with the formation of bridged structures. Thus it was demonstrated that N, N'-diphenylethylenediamine reacts readily with formaldehyde to give a stable cyclic productº. It might be expected, therefore, that FH, which is also a I: 2-diamine, would react with formal-dehyde to give III, and that this compound would be stabilized to oxygen by the presence of the firmly bound methylene bridge. Although the product of formaldehyde reaction with FH, was found to be somewhat more stable than FH, itself, it was nevertheless very sensitive to oxygen, for in aqueous solution it rapidly lost coenzyme activity when shaken under air". This sensitivity to oxygen has been confirmed by spectrophotometric studies. When a solution of FH, is diluted with phosphate buffer (pH 7-2) to a concentration of 5 x 10-* M the spectrum changes within a few minutes from that of FH,(X. 298 mp.) to that of oxidized products with?. at shorter wave-lengths (finally 275 mp.). If the diluent contains formaldehyde the rate of change due to oxidation is less, but even in the presence of 10-* M formaldehyde it is about 3 per cent of that occurring in absence of formaldehyde. In this laboratory, paper chromatography of reaction mixtures has yielded no clear separation of a product with Rp different from that of FH, as reported by others*. These results were at first interpreted as indicating that II must, be the structure of the product, and that it must readily dissociate*.*. Investigation of the binding of formaldehyde labelled with carbon-14 by FH, and related hydropteridines indicated that approximately one molecular proportion of formalde-hyde was bound by FH, smaller amounts by Nº"-formylFH, and 2-amino-4-hydroxy-6-methyltetrahydropteridine and a negligible amount by leuco-vorin. These results have been confirmed and extended by determination of the formaldehyde concentration in equilibrium with known concentrations of hydropteridines. Since tetrahydropteridine is rather unstable, tetrahydroquinoxaline, a close