inosinic-acid and ribose-1-phosphate

A variant clone of cultured chinese hamster lung fibroblasts (V79), selected for resistance to 8-azaguanine (V79 azagrst), although lacking hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8), is able to convert hypoxanthine into IMP via purine-nucleoside phosphorylase (EC 2.4.2.1) and nucleoside kinase. In addition to the phosphoribosylation pathway, we also present evidence for the occurrence of a kinase-mediated pathway of recovery of hypoxanthine in the wild-type cells. The lower rate of formation of IMP in the V79 azagrst cells, apparently correlated with the phosphorylation of the nucleoside, suggests possible differences in the catalytic and/or regulatory properties of nucleoside kinase in the two cell lines. This fact might be of particular relevance in evaluating the mechanisms of resistance to purine analogs displayed by several cell types.

Topics: Animals; Azaguanine; Cell Line; Cricetinae; Cricetulus; Drug Resistance; Hypoxanthine; Hypoxanthine Phosphoribosyltransferase; Hypoxanthines; Inosine Monophosphate; Lung; Pentosephosphates; Phosphoribosyl Pyrophosphate; Phosphotransferases; Purine-Nucleoside Phosphorylase; Ribosemonophosphates

1. Intact human red cells do not attack exogenous IMP. The nucleotide is readily broken down by the soluble erythrocyte fraction to inosine, hypoxanthine and ribose 1-phosphate, with a pH optimum of approx. 6.2. 2. Ribose 1-phosphate can be actively reutilized, in the presence of ATP and hypoxanthine, to give IMP, at pH 7.4. The velocity of the IMP salvage synthesis dramatically increases at more alkaline pH values. 3. The two curves relating the velocities of IMP breakdown and of IMP synthesis as a function of hydrogen ion concentration intersect at pH 7.4. 4. The observations might be relevant in the process of purine transport by red cells.

Topics: Carbon Radioisotopes; Erythrocytes; Humans; Inosine Monophosphate; Inosine Nucleotides; Kinetics; Pentosephosphates; Phosphates; Ribosemonophosphates