Studies of Fluorinated Pyrimidines. XVIII. The Degradation of 5-Fluoro-2′-deoxyuridine and Related Compounds by Nucleoside Phosphorylase

Abstract

The degradation of 5-fluoro-2 ′-deoxyuridine and a variety of other nucleosides to the corresponding pyrimidine bases by the high-speed (105,000 × g) supernatant fraction of Ehrlich ascites cells has been investigated. Both 5-fluoro-2′-deoxyuridine and 5-fluorouridine were degraded rapidly by this preparation at pH optima of 6.4 and 7.4, respectively. A number of other pyrimidine nucleosides, in particular 2 ′-deoxyuridine and the 5-halogen-substituted derivatives of 2′-deoxyuridine, were also degraded to the free bases at varying rates under the same conditions. 3 ′-Monoacetyl-5-fluoro-2′-deoxyuridine and 3′,5′-diacetyl-5-fluoro-2′-deoxyuridine were not degraded by the high-speed supernatant fraction of Ehrlich ascites cells or of human, rat, or mouse liver. However, powerful deacetylase activity was found in a particulate fraction from liver; only very weak deacetylase activity was present in Ehrlich ascites cells. The phosphorylase activity of Ehrlich ascites cells towards 5-fluoro-2 ′-deoxyuridine was inhibited by several compounds, in particular by 5-fluorouridine and uridine. Uridine was found to be a competitive inhibitor of the reaction. © 1963, American Chemical Society. All rights reserved.