Uracil salvage pathway in PC12 cells

The salvage anabolism of uracil to pyrimidine ribonucleosides and ribonucle otides was investigated in PC12 cells. Pyrimidine base phosphoribosyl trans ferase is absent in PC12 cells. As a consequence any uracil or cytosine sal vage must be a 5-phosphoribosyl l-pyrophosphate-independent process. When P C12 cell extracts were incubated with ribose I-phosphate, ATP and uracil th ey can readily catalyze the synthesis of uracil nucleotides, through a salv age pathway in which the ribose moiety of ribose I-phosphate is transferred to uracil via uridine phosphorylase (acting anabolically), with subsequent uridine phosphorylation. This pathway is similar to that previously descri bed by us in rat liver and brain extracts (Cappiello et al., Biochim. Bioph ys. Acta 1425 (1998) 273, Mascia et al., Biochim. Biophys. Acta 1472 (1999) 93). We show using intact PC12 cells that they can readily take up uracil from the external medium. The analysis of intracellular metabolites reveals that uracil taken up is salvaged into uracil nucleotides, with uridine as an intermediate. We propose that the ribose l-phosphate-dependent uracil sa lvage shown by our in vitro studies, using tissues or cellular extracts, mi ght also be operative in intact cells. Our results must be taken into consi deration for the comprehension of novel chemotherapeutics' influence on pyr imidine neuronal metabolism. (C) 2000 Elsevier Science B.V. All rights rese rved.