The metabolism of the erythrocyte. XVIII. Inhibition of nucleotide synthesis in human erythrocytes by adenosine

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Abstract
Incubation of human erythrocytes with glucose and 1.5 mM adenine for 12 h doubles the intracellular level of ATP because of synthesis of the nucleotide from the purine. The effect of the nucleosides inosine, guanosine, and adenosine on the synthesis of nucleotide labile phosphate during the incubation was studied. Inosine and guanosine had no effect, but adenosine, in concentrations between 10 and 20 mM, inhibited the increase in labile phosphate and the incorporation of adenine-8-14C into ATP. The adenosine has no effect on the slight incorporation of adenine-8-14C into, or the intracellular concentration of, ADP or AMP. The inhibition is not due to the formation of ammonia and (or) inosine resulting from the deamination of adenosine, nor is it due to the change of pH produced by the ammonia. Adenosine must be present to produce its inhibitory effect and the inhibition can be reversed by removal of the nucleoside, either by washing the cells or through the action of the erythrocyte adenosine deaminase. It thus appears that adenosine produces its effect when it is present in concentrations too great to be completely deaminated. A small proportion (0.5%) of the added adenosine is incorporated into the cellular nucleotides, more than half into IMP, resulting in a marked increase in the concentration of this nucleotide. It is suggested that adenosine acts by inhibition of the synthesis of either 5-phosphoribosyl-1-pyrophosphate or adenylic acid.
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