SYNERGISTIC ACTION OF ADP AND 2,3-BISPHOSPHOGLYCERATE ON THE MODULATION OF CYTOSOLIC 5'-NUCLEOTIDASE

Cytosolic 5'-nucleotidase, acting preferentiallly on IMP, GMP and thei r deoxyderivatives, can also behave as a phosphotransferase, operating a transfer of phosphate from a nucleoside monophosphate donor to a nu cleoside acceptor which, besides a natural nucleoside, can be also an analog. The enzyme activity is stimulated by ADP, ATP and 2,3-bisphosp hoglycerate (BPG). The concentration of effector required to attain ha lf maximal activation (A(0.5)) for the bisphosphorylated compound is i n the millimolar range, so that BPG seems to act as a physiological ac tivator of 5'-nucleotidase only in erythrocytes. However, the combinat ion of BPG and ADP brings about a significant increase of their respec tive affinity for the enzyme, lowering their A(0.5) values approx. 4-t imes. The observation that BPG favors the phosphotransferase more than the hydrolase activity of 5'-nucleotidase stands for a key role of th is metabolite in the regulation of the processes of activation of puri ne pro-drugs, in which this enzyme is involved.