The relationship between purines, pyrimidines, nucleosides, and glutamine for fibroblast cell proliferation

Previous studies indicate that glutamine is a critical requirement for cell proliferation in vitro. We recently showed that depletion of glutamine from the culture medium supporting growing cells significantly reduced the proportion of cells undergoing DNA synthesis. Similarly glutamine depletion significantly reduced the stimulatory response of quiescent cells to 10% serum. This study shows that the inhibitory effects of depletion of glutamine--in either of these two situations--can be overcome by the addition of adenine or adenosine. Adenine was the only nitrogen base and adenosine was the only nucleoside for which this effect was observed. Such effects could, however, also be achieved by addition of the purine metabolites hypoxantine and inosine. Furthermore, it was found that glutamine (or adenine/adenosine) is only required during a limited interval coinciding with the late part of the G1-phase and the beginning of S-phase. These data suggest the possibility that glutamine exerts its main regulatory effects on cell proliferation by acting as a precursor for adenine and adenosine.