Nucleotide catabolism and nucleoside cycles in human thymocytes. Role of orthophosphate

The catabolism of GTP and ATP in intact human thymocytes was studied, and the effect of intracellular Pi concentrations on various catabolic reactions was evaluated. Induction of nucleotide catabolism was performed with either NaN3 or deoxyglucose. NaN3 induced an increase in intracellular Pi, whereas deoxyglucose induced a decrease in Pi in human thymocytes. At elevated Pi concentrations, an intracellular accumulation of GMP, IMP and AMP was observed, and the entry of these nucleotides into the nucleoside cycles was diminished. In contrast, at lowered Pi concentrations, there was no accumulation of nucleoside monophosphates, but the production of purine bases and nucleosides was increased as a result of enhanced nucleotide entry into the nucleoside cycles. The dephosphorylation of nucleotides thus seems to be regulated by intracellular Pi concentrations. ATP catabolism proceeded mainly via adenylate deamination at both elevated and lowered Pi concentrations. Guanylate formed during GTP catabolism was mainly dephosphorylated, but significant amounts of GMP were also deaminated to yield IMP.