Hamada A, Fukushima S, Saneyoshi M, Kawaguchi T, Nakano M
Department of Pharmacy, Kumamoto University Hospital, Japan.
Biol Pharm Bull. 1995 Jan;18(1):172-5. doi: 10.1248/bpb.18.172.
This study examined the inhibitory effect of acyclopyrimidinenucleosides on 5'-deoxy-5-fluorouridine (5'-DFUR) phosphorolysis in intestinal tissue derived from rabbit, rat, mouse, and human. 5-Bromoacyclouridine, 5-fluoroacyclouridine, acyclouridine, and 5-nitroacyclouridine showed little or only moderate effect, but acyclothymidine [5-methyl-1-(2'-hydroxyethoxymethyl)uracil] showed strong inhibitory effect on 5'-DFUR phosphorolysis in intestinal tissue homogenates derived from human. In the absence of inhibitor (acyclothymidine), the Vmax of 5'-DFUR phosphorolysis was 2.66 mumol/min and the Km was 0.57 mM in human intestinal homogenates. The Vmax was unaltered by increased inhibitor concentration. The maximal inhibitory effect of acyclothymidine on 5'-DFUR phosphorolysis in rat homogenates was over 90%. The Ki/Km was 0.63 in human, 2.14 in rabbit, 1.09 x 10(-2) in rat, and 1.71 x 10(-2) in mouse. These data show that acyclothymidine is a competitive inhibitor of 5'-DFUR phosphorolysis, and that it can inhibit not only uridine phosphorylase but also thymidine phosphorylase.
本研究检测了无环嘧啶核苷对兔、大鼠、小鼠和人肠道组织中5'-脱氧-5-氟尿苷（5'-DFUR）磷酸解作用的抑制效果。5-溴无环尿苷、5-氟无环尿苷、无环尿苷和5-硝基无环尿苷显示出很小或仅中等程度的作用，但无环胸苷[5-甲基-1-(2'-羟基乙氧基甲基)尿嘧啶]对人肠道组织匀浆中的5'-DFUR磷酸解作用显示出很强的抑制效果。在不存在抑制剂（无环胸苷）的情况下，人肠道匀浆中5'-DFUR磷酸解作用的Vmax为2.66 μmol/min，Km为0.57 mM。增加抑制剂浓度时Vmax未改变。无环胸苷对大鼠匀浆中5'-DFUR磷酸解作用的最大抑制效果超过90%。人、兔、大鼠和小鼠的Ki/Km分别为0.63、2.14、1.09×10⁻²和1.71×10⁻²。这些数据表明无环胸苷是5'-DFUR磷酸解作用的竞争性抑制剂，并且它不仅可以抑制尿苷磷酸化酶，还可以抑制胸苷磷酸化酶。
