Christa L, Thuillier L, Munier A, Perignon J L
Biochim Biophys Acta. 1984 Feb 17;803(1-2):7-10. doi: 10.1016/0167-4889(84)90048-x.
5'-Deoxy-5'-methylthioadenosine, a by-product of polyamine metabolism, is a potent inhibitor of cell proliferation. MTA phosphorylase cleaves MTA into adenine and 5'-methylthioribose-1-P. We studied MTA inhibition and salvage into purine compounds and methionine in concanavalin A-stimulated rat T lymphocytes and in Raji cells. When de novo purine synthesis was inhibited by azaserine (20 microM), low concentrations of MTA, (less than or equal to 20 microM), were able to completely restore cell proliferation in both types of cells. When cells were cultured in a methionine-free medium, MTA (15 microM) completely fulfilled the methionine requirement of Raji cells but only 50% of that of rat T lymphocytes. MTA displayed a dose-dependent inhibition of the proliferation of both types of cells, but in the case of MTA salvage into purines or methionine, the curves were shifted to higher MTA concentrations. In vitro studies by Backlund et al. (Backlund, P.S., Chang, C.P. and Smith, R.A. (1982) J. Biol. Chem. 257, 4196-4202) on rat liver homogenates, suggested that the last step of MTA salvage into methionine may be the transamination of 2-keto-4-methylthiobutyrate to methionine. We present evidence that this is a step physiologically efficient in intact cells.
5'-脱氧-5'-甲硫基腺苷是多胺代谢的副产物，是一种有效的细胞增殖抑制剂。MTA磷酸化酶将MTA裂解为腺嘌呤和5'-甲硫基核糖-1-磷酸。我们研究了刀豆球蛋白A刺激的大鼠T淋巴细胞和Raji细胞中MTA对嘌呤化合物和蛋氨酸的抑制作用及补救作用。当氮杂丝氨酸（20微摩尔）抑制嘌呤从头合成时，低浓度的MTA（小于或等于20微摩尔）能够完全恢复两种细胞类型的细胞增殖。当细胞在无蛋氨酸培养基中培养时，MTA（15微摩尔）完全满足Raji细胞的蛋氨酸需求，但仅满足大鼠T淋巴细胞蛋氨酸需求的50%。MTA对两种细胞类型的增殖均表现出剂量依赖性抑制，但在MTA补救合成嘌呤或蛋氨酸的情况下，曲线向更高的MTA浓度偏移。Backlund等人（Backlund, P.S., Chang, C.P.和Smith, R.A. (1982) J. Biol. Chem. 257, 4196 - 4202）对大鼠肝脏匀浆的体外研究表明，MTA补救合成蛋氨酸的最后一步可能是2-酮-4-甲硫基丁酸转氨生成蛋氨酸。我们提供的证据表明，这一步在完整细胞中具有生理效率。
