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Inhibition of imp specific cytosolic 5' nucleotidase and adenosine formation in rat polymorphonuclear leukocytes by 5' deoxy 5' isobutylthio derivatives of adenosine and inosine

Inhibition of imp specific cytosolic 5' nucleotidase and adenosine formation in rat polymorphonuclear leukocytes by 5' deoxy 5' isobutylthio derivatives of adenosine and inosine

Biochemical Journal 262(1): 203-208

1. The partially purified IMP-specific cytosolic 5'-nucleotidases from rat liver, polymorphonuclear leucocytes and heart were inhibited by 50% by 2-6 mM-5'-deoxy-5'-isobutylthioadenosine (IBTA) or 7-10 mM-5'-deoxy-5'-isobutylthioinosine (IBTI). IBTA and IBTI inhibited the rat liver and polymorphonuclear-leucocyte enzymes non-competitively. IBTA, but not IBTI, also inhibited the ecto-5'-nucleotidase of polymorphonuclear leucocytes. IBTI was, by contrast, a more potent inhibitor than IBTA of the AMP-specific soluble 5'-nucleotidase from pigeon heart. 2. During 2-deoxyglucose-induced ATP-catabolism in rat polymorphonuclear leucocytes, adenosine formation was inhibited by approx. 80% by 3 mM-IBTA and by approx. 70% by 7 mM-IBTI. 3. The results show that 5'-modified nucleosides are inhibitors of cytosolic 5'-nucleotidases and that they penetrate to inhibit their target enzymes in intact cells. Such inhibitors may be useful of clarify the mechanisms of adenosine formation and to prevent mononucleotide hydrolysis during ATP breakdown.

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Accession: 007464596

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PMID: 2554883

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