Evidence for distinct catabolic pathways for deoxy-GTP and GTP in purine-nucleoside phosphorylase-deficient mouse T...

The catabolism of deoxy-GTP and GTP was compared in purine-nucleoside phosphorylase-deficient mouse T lymphoblasts. It was found that guanine ribonucleotides and deoxyribonucleotides are degraded by distinct pathways in cells cultured under both physiological and induced catabolic conditions. In T lymphoblasts, cultured under physiological conditions, 50% of the GMP formed during GTP catabolism was dephosphorylated and 50% was deaminated, whereas in the presence of the catabolic inducer deoxyglucose 90% of the GMP formed was dephosphorylated and only 10% was deaminated. These results indicate that GTP catabolism in lymphoblasts proceeds by alternative pathways, either via GMP dephosphorylation or via GMP reductive deamination, and physiological conditions determine with pathway will be used. In contrast, deoxy-GTP catabolism proceeds exclusively via deoxy-GMP dephosphorylation under both physiological and induced catabolic conditions. The lack of deoxy-GMP deamination may contribute to the accumulation of cytotoxic levels of deoxyguanosine found in purine-nucleoside phosphorylase-deficient patients.