Arnér E S, Eriksson S
Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Sweden.
Pharmacol Ther. 1995;67(2):155-86. doi: 10.1016/0163-7258(95)00015-9.
The mammalian deoxyribonucleoside kinases are deoxycytidine kinase, thymidine kinase 1 and 2 and deoxyguanosine kinase. These enzymes phosphorylate deoxyribonucleosides and thereby provide an alternative to de novo synthesis of DNA precursors. Their activities are essential for the activation of several chemotherapeutically important nucleoside analogues. In recent years, these enzymes have been thoroughly characterised with regard to structure, substrate specificity and patterns of expression. In this review, these results are reviewed and furthermore, the physiologic metabolic role of the anabolic enzymes is discussed in relation to catabolic pathways. The significance of this information for the development of therapeutic protocols and choice of animal model systems is discussed. Finally, alternative pathways for nucleoside analogue phosphorylation are surveyed, such as the phosphotransfer capacity of 5'-nucleotidase.
哺乳动物的脱氧核糖核苷激酶包括脱氧胞苷激酶、胸苷激酶1和2以及脱氧鸟苷激酶。这些酶使脱氧核糖核苷磷酸化，从而为DNA前体的从头合成提供了一种替代途径。它们的活性对于激活几种具有重要化疗意义的核苷类似物至关重要。近年来，这些酶在结构、底物特异性和表达模式方面已得到充分表征。在本综述中，对这些结果进行了回顾，此外，还讨论了合成代谢酶与分解代谢途径相关的生理代谢作用。讨论了这些信息对于治疗方案开发和动物模型系统选择的意义。最后，对核苷类似物磷酸化的替代途径进行了综述，例如5'-核苷酸酶的磷酸转移能力。
