Sugita Y, Yamauchi H, Omine M, Maekawa T
Third Department of Internal Medicine, Gunma University School of Medicine, Japan.
Int J Hematol. 1996 Oct;64(3-4):203-12. doi: 10.1016/0925-5710(96)00501-4.
The biochemical basis underlying the pathogenesis of megaloblastic anemia due to vitamin B12 deficiency was examined. Megaloblastic bone marrow cells show a marked imbalance in the deoxynucleoside triphosphate pools. If cellular dUTP concentration is elevated due to metabolic block in a similar way to dCTP, ensuing uracil misincorporation into DNA would result in deranged DNA composition and impaired cell function. Therefore, dUTP-degrading activity was measured in blood cells from various diseases. dUTPase (dUTP nucleotidohydrolase) activity of bone marrow cells was, on average, 4.4 times higher in 8 patients with untreated megaloblastic anemia than that of other normoblastic conditions. Such elevated dUTPase may help lower cellular dUTP levels in megaloblastic anemia. However, it is not clear whether the observed increase of dUTPase in megaloblastic cells is sufficient to suppress uracil misincorporation below the harmful level.
对维生素B12缺乏所致巨幼细胞贫血发病机制的生化基础进行了研究。巨幼细胞骨髓细胞的脱氧核苷三磷酸池存在明显失衡。如果细胞dUTP浓度因代谢阻滞而以与dCTP类似的方式升高，随后尿嘧啶错误掺入DNA会导致DNA组成紊乱和细胞功能受损。因此，对各种疾病患者血细胞中的dUTP降解活性进行了测定。8例未经治疗的巨幼细胞贫血患者骨髓细胞的dUTPase（dUTP核苷酸水解酶）活性平均比其他正常成红细胞情况高4.4倍。这种升高的dUTPase可能有助于降低巨幼细胞贫血中的细胞dUTP水平。然而，尚不清楚在巨幼细胞中观察到的dUTPase增加是否足以将尿嘧啶错误掺入抑制到有害水平以下。
