Rodaway S, Marcus A
J Biol Chem. 1980 Sep 25;255(18):8402-4.
The cytostatic effect of 6-azauridine on cell growth is generally regarded to be a consequence of the inhibition of de novo pyrimidine biosynthesis by the metabolite, 6-azauridine 5'-monophosphate. We show here that wheat embryonic axes further metabolize 6-azauridine to the 5'-triphosphate and incorporate the analogue into RNA, thus offering an alternative mechanism for growth inhibition. At a level of 6-azauridine required to maximally inhibit UTP biosynthesis, the ratio of 6-azaUTP to UTP is about 2:1 and substitution of 6-azauridine for uridine in new RNA is on the order of 1 in 18. The new metabolites of 6-azauridine are identified by high pressure and thin layer chromatography coupled with enzyme treatments.
6-氮杂尿苷对细胞生长的细胞抑制作用通常被认为是其代谢产物6-氮杂尿苷5'-单磷酸抑制嘧啶从头生物合成的结果。我们在此表明，小麦胚轴会将6-氮杂尿苷进一步代谢为5'-三磷酸，并将该类似物掺入RNA中，从而为生长抑制提供了另一种机制。在最大程度抑制UTP生物合成所需的6-氮杂尿苷水平下，6-氮杂UTP与UTP的比例约为2:1，新RNA中6-氮杂尿苷取代尿苷的比例约为1/18。通过高压和薄层色谱结合酶处理鉴定了6-氮杂尿苷的新代谢产物。
