Control of pteridine biosynthesis in the natural killer-like cell line YT

The natural killer-like cell line YT constitutively expresses GTP-cyclohydrolase activity whereas 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase are absent. The product, dihydroneopterin triphosphate, is dephosphorylated and oxidized causing neopterin to accumulate in the cells. The activities of the H4biopterin synthesizing enzymes are not controlled by IFN-gamma or the synergistic action of both IFN-gamma and IL-2 as has been shown for monocytes/macrophages (Huber C. et al. (1984) J. Exp. Med. 160, 310) and CD4+ T cells, respectively (Ziegler I. et al. (1990) J. Biol. Chem. 265, 17026). Sepiapterin reductase specifically is induced by incubation of the cells with sepiapterin, leaving GTP-cyclohydrolase, 6-pyruvoyltetrahydropterin synthase and other enzymes related to pteridine metabolism (dihydropteridine reductase, dihydrofolate reductase) unaffected. The data indicate that H4biopterin synthesis is individually regulated in the diverse cellular components of the immune system.