Regulation of deoxyadenosine and nucleoside analog phosphorylation by human placental adenosine kinase.
The enzymes responsible for phosphorylation of adenosine and nucleoside analogs are important in the pathogenesis of adenosine deaminase deficiency and for the activation of specific anticancer and antiviral drugs. We examined the role of adenosine kinase in catalyzing these reactions using an enzyme purified 4000-fold (2.1 umol/min/mg) from human placenta. The Km values of adenosine and ATP are 135 uM and 4 uM, respectively. Adenosine kinase phosphorylates adenine arabinoside with an apparent Km value of 1 mM using adenosine kinase assay conditions. The Km values for 6-methylmercaptopurine riboside and 5-iodotubercidin, substrates for adenosine kinase, are estimated to be 4.5 uM and 2.6 nM, respectively. These data indicate that dadenosine phosphorylation by adenosine kinase is primarily regulated by its Km, and the concentrations of Mg2+, ADP and AMP. The high Km values for phosphorylation of dadenosine and adenine arabinoside suggest that adenosine kinase may be less likely to phosphorylate these nucleosides in vivo than other enzymes with lower Km values. Adenosine kinase appears to be important for adenosine analog phosphorylation where the Michaelis constant is in the low micromolar range.
D000241:Adenosine / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D003839:Deoxyadenosines / Q000378:metabolism*; D005260:Female; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009705:Nucleosides / Q000494:pharmacology; D010770:Phosphotransferases / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D013379:Substrate Specificity; D014740:Vidarabine / Q000378:metabolism
D003839:Deoxyadenosines; D009705:Nucleosides; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D000248:Adenosine Kinase; D014740:Vidarabine; D000241:Adenosine