利巴韦林和viramidine腺苷激酶的磷酸化和胞质5核苷酸酶II:对利巴韦林在红细胞代谢。
文章的细节
-
引用
复制到剪贴板 -
吴生理改变,拉尔森G,沃克H,垫片JH,香港Z
利巴韦林和viramidine腺苷激酶的磷酸化和胞质5核苷酸酶II:对利巴韦林在红细胞代谢。
Antimicrob代理Chemother。2005年6月,49 (6):2164 - 71。
- PubMed ID
-
15917509 (在PubMed]
- 文摘
-
许多模拟核苷药物,如利巴韦林、viramidine被激活或代谢体内到5的磷酸化。在这个报告中,我们确定了稳态动力学参数为5的利巴韦林-monophosphorylation viramidine腺苷酸激酶。利巴韦林的明显公里540 microM, k (cat)是1.8最低为1。其催化效率为3.3 x 10(3)最低为1。microM-1 1200倍低于腺苷。与利巴韦林普遍认为是完全由腺苷酸激酶磷酸化,胞质5 '二核苷酸酶被发现在体外促进利巴韦林磷酸化。反应的最佳刺激生理浓度的ATP或2,3-bisphosphoglycerate。3-bisphosphoglycerate磷酸盐+ ATP和2,利巴韦林的明显公里88 microM, k (cat)是4.0最低为1。这些发现表明,胞质5 '二核苷酸酶可能参与利巴韦林体内磷酸化。像利巴韦林,viramidine被发现磷酸化通过腺苷酸激酶或胞质5核苷酸酶II,虽然低得多的活动。 The catalytic efficiency for viramidine phosphorylation is 10- to 330-fold lower than that of ribavirin, suggesting that other nucleoside kinase(s) may be involved in viramidine phosphorylation in vivo. Both ribavirin and viramidine are not phosphorylated by deoxycytidine kinase and uridine-cytidine kinase. The coincidence of presence of high concentrated 2,3-bisphosphoglycerate in erythrocytes suggests that cytosolic 5'-nucleotidase II could play an important role in phosphorylating ribavirin and contribute to anabolism of ribavirin triphosphate in erythrocytes. Elucidation of ribavirin and viramidine phosphorylation mechanism should shed light on their in vivo metabolism, especially the ribavirin-induced hemolytic anemia in erythrocytes.