High uridine catabolic activity in cultured human melanoma cells.

Abstract

Uridine (Urd) Phosphorylase catalyzes the reversible reaction, Urd + Pi ⇋ uracil + ribose 1-phosphate. In cancer chemotherapy, Urd Phosphorylase has a potential role in the action of some antipyrimidine drugs. One of the possible means for the conversion of 5-fluorouracil to active nucleotide forms involves Urd Phosphorylase and Urd kinase1. The catabolic activity of Urd Phosphorylase is required for the activity of 5′-deoxy-5-fluoro-uridine which cannot be phosphorylated by kinases and must first be cleaved to 5-fluorouracil2,3. Urd Phosphorylase may also be an important enzyme in the salvage pathway synthesis of normal pyrimidine nucleotides. In the anabolic direction Urd Phosphorylase, together with Urd kinase, may provide for salvage of uracil. Conversely, the degradative activity of Urd Phosphorylase could reduce the availability of Urd for nucleotide synthesis. The action of inhibitors of de novo pyrimidine nucleotide synthesis may be compromised by Urd4,5. Urd Phosphorylase activity has not been adequately investigated as a factor in the salvage pathway synthesis of pyrimidine nucleotides. In the present study we compared several human and murine cell lines and different human tumors with respect to Urd Phosphorylase and Urd kinase activities to assess in these cells and tissues the potential metabolism of Urd. The data show that human melanoma cells contain high levels of Urd Phosphorylase which may determine the cellular capacity for Urd degradation.