Synergistic action of ADP and 2,3-bisphosphoglycerate on the modulation of cytosolic 5'-nucleotidase.
Cytosolic 5'-nucleotidase, acting preferentially on IMP, GMP and their deoxyderivatives, can also behave as a phosphotransferase, operating a transfer of phosphate from a nucleoside monophosphate donor to a nucleoside acceptor which, besides a natural nucleoside, can be also an analog. The enzyme activity is stimulated by ADP, ATP and 2,3-bisphosphoglycerate (BPG). The concentration of effector required to attain half maximal activation (A0.5) for the bisphosphorylated compound is in the millimolar range, so that BPG seems to act as a physiological activator of 5'-nucleotidase only in erythrocytes. However, the combination of BPG and ADP brings about a significant increase of their respective affinity for the enzyme, lowering their A0.5 values approx. 4-times. The observation that BPG favors the phosphotransferase more than the hydrolase activity of 5'-nucleotidase stands for a key role of this metabolite in the regulation of the processes of activation of purine pro-drugs, in which this enzyme is involved.
Pesi
R
R
Istituto di Chimica Biologica, Sassari, Italy.
Baiocchi
C
C
Tozzi
M G
MG
Camici
M
M
D019794:2,3-Diphosphoglycerate; D015720:5'-Nucleotidase / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D003600:Cytosol / Q000201:enzymology; D004163:Diphosphoglyceric Acids / Q000494:pharmacology*; D004357:Drug Synergism; D007700:Kinetics; D013950:Thymus Gland / Q000201:enzymology*; D014638:Vanadates / Q000494:pharmacology
D004163:Diphosphoglyceric Acids; D019794:2,3-Diphosphoglycerate; D014638:Vanadates; D000244:Adenosine Diphosphate; D015720:5'-Nucleotidase