Della Ragione F, Pegg A E
Biochem J. 1983 Feb 15;210(2):429-35. doi: 10.1042/bj2100429.
The effects of a number of nucleosides related to 5'-methylthioadenosine on the activities of S-adenosylhomocysteine hydrolase, 5'-methylthioadenosine phosphorylase, spermidine synthase and spermine synthase were investigated. Both 5'-methylthioadenosine and 5'-isobutylthioadenosine gave rise to an enzyme-activated irreversible inhibition of S-adenosylhomocysteine hydrolase, but 5'-methylthiotubercidin (5'-methylthio-7-deaza-adenosine), 5'-deoxy-5'-chloroformycin, 5'-ethylthio-2-fluoro-adenosine and 1,N6-etheno-5'-methylthioadenosine were totally ineffective in producing this inactivation. Of the nucleosides tested, only 5'-methylthioadenosine, 5'-methylthiotubercidin and 5'-isobutylthioadenosine were inhibitory towards the aminopropyltransferases responsible for the synthesis of spermine and spermidine. 5'-Methylthiotubercidin, 5'-deoxy-5'-chloroformycin and 5'-isobutylthioadenosine were inhibitors of the degradation of 5'-methylthioadenosine by 5'-methylthioadenosine phosphorylase, but only 5'-isobutylthioadenosine was also a substrate for this enzyme. These results suggest that the effects of 5'-isobutylthioadenosine of the cell may result from the combination of inhibitory actions on polyamine synthesis, 5'-methylthioadenosine degradation and S-adenosylhomocysteine degradation. The resulting increased concentrations of S-adenosylhomocysteine could bring about inhibition of methyltransferase reactions. A new convenient method for the assay of S-adenosylhomocysteine hydrolase in the direction of synthesis is described.
研究了一系列与5'-甲硫基腺苷相关的核苷对S-腺苷同型半胱氨酸水解酶、5'-甲硫基腺苷磷酸化酶、亚精胺合成酶和精胺合成酶活性的影响。5'-甲硫基腺苷和5'-异丁硫基腺苷均可引起S-腺苷同型半胱氨酸水解酶的酶激活不可逆抑制，但5'-甲硫基杀结核菌素（5'-甲硫基-7-脱氮腺苷）、5'-脱氧-5'-氯甲酸霉素、5'-乙硫基-2-氟腺苷和1,N6-乙烯基-5'-甲硫基腺苷在产生这种失活方面完全无效。在所测试的核苷中，只有5'-甲硫基腺苷、5'-甲硫基杀结核菌素和5'-异丁硫基腺苷对负责精胺和亚精胺合成的氨基丙基转移酶有抑制作用。5'-甲硫基杀结核菌素、5'-脱氧-5'-氯甲酸霉素和5'-异丁硫基腺苷是5'-甲硫基腺苷磷酸化酶降解5'-甲硫基腺苷的抑制剂，但只有5'-异丁硫基腺苷也是该酶的底物。这些结果表明，5'-异丁硫基腺苷对细胞的作用可能是由于对多胺合成、5'-甲硫基腺苷降解和S-腺苷同型半胱氨酸降解的抑制作用共同导致的。由此导致的S-腺苷同型半胱氨酸浓度升高可能会抑制甲基转移酶反应。描述了一种新的方便的合成方向上测定S-腺苷同型半胱氨酸水解酶的方法。
