Inhibition of 5'-Deoxy-5-fluorouridine Phosphorolysis by Acyclopyrimidinenucleosides in Intestinal Tissue Homogenates

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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 V_<max> of 5'-DFUR phosphorolysis was 2.66 μmol/min and the K_m was 0.57 mM in human intestinal homogenates. The V_<max> was unaltered by increased inhibitor concentration. The maximal inhibitory effect of acyclothymidine on 5'-DFUR phosphorolysis in rat homogenates was over 90%. The K_i/K_m was 0.63 in human, 2.14 in rabbit, 1.09×10^<-2> in rat, and 1.71×10^<-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.
社団法人日本薬学会の論文
1995-01-15