Effects of deoxyadenosine triphosphate and 9-beta-D-arabinofuranosyl-adenine 5'-triphosphate on human ribonucleotide reductase from Molt-4F cells and the concept of "self-potentiation".
Deoxyadenosine triphosphate (dATP) acted as a noncompetitive inhibitor with respect to the specific nucleoside triphosphate activator for the reduction of all four common ribonucleoside diphosphates catalyzed by the reductase derived from human Molt-4F (T-type lymphoblast) cells. The inhibition constant of dATP for different ribonucleotide reduction reactions was different, indicating that the binding of the nucleoside triphosphate activator or substrate could modify the binding affinity of dATP to the enzyme. dATP also acted as a noncompetitive inhibitor with respect to cytidine diphosphate (CDP) for reductase-catalyzed CDP reduction. 9-beta-D-Arabinofuranosyl-adenine 5'-triphosphate acted as a competitive inhibitor with respect to either adenosine triphosphate or guanosine triphosphate for CDP or for adenosine diphosphate reduction, respectively. The inhibition constant was 15 microM for CDP reduction and 4 microM for adenosine diphosphate reduction. 1-beta-D-Arabinofuranosyladenine 5'-triphosphate could not substitute for adenosine triphosphate or guanosine triphosphate as the activator for CDP or adenosine diphosphate reduction, respectively. The effects of 9-beta-D-arabinofuranosylcytosine 5'-triphosphate and 5-iodo-2'-deoxyuridine 5'-triphosphate on ribonucleotide reductase were also included for comparison. The "self-potentiation" mechanism of the action of 9-beta-D-arabinofuranosyladenine and 5-iodo-2'-deoxyuridine is discussed.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001088:Arabinonucleotides / Q000494:pharmacology*; D002460:Cell Line; D003565:Cytidine Diphosphate / Q000378:metabolism; D003838:Deoxyadenine Nucleotides / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000201:enzymology*; D011485:Protein Binding; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology*
D001088:Arabinonucleotides; D003838:Deoxyadenine Nucleotides; D004791:Enzyme Inhibitors; D001084:Vidarabine Phosphate; C000101:ara-ATP; D000244:Adenosine Diphosphate; D003565:Cytidine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D012264:Ribonucleotide Reductases; C026600:2'-deoxyadenosine triphosphate