Abstract
The phosphorylation of dadenosine and nucleoside analogs is important in adenosine deaminase deficiency and for specific anticancer and antiviral drugs. We examined the regulation of nucleoside phosphorylation by adenosine kinase purified 4000-fold (2.1 μmol/min/mg). The Km values of dadenosine and ATP were 135 μM and 4 μM, respectively. Potassium and magnesium are absolute requirements for dadenosine phosphorylation and 150 mM potassium and 5 mM MgCl2 are critical for linear kinetics. At 0.4 mM MgCl2 in excess of ATP levels, the Km for dadenosine increased 10-fold. ADP is a competitive inhibitor with a Ki of 13 μM with variable MgATP2-, while it is a mixed inhibitor with a Ki and Ki' of 600 μM and 92 μM, respectively, when dadenosine is variable. AMP is a mixed inhibitor with Ki and Ki' of 180 μM and 20 μM, respectively, with variable dadenosine. Adenosine kinase phosphdrylates adenine arabinoside (ara-A) with an apparent Km value of 1 mM. The Km values for 6-methylmercapto-purine riboside and 5-iodotubercidin were estimated to be 7 μM and 3 nM, respectively. These data indicate that dadenosine phosphorylation is regulated by its Km, and levels of Mg, ADP, and AMP. The high Km values for phosphorylation of dadenosine and ara-A suggest that adenosine kinase may have a limited role for phosphorylation of these nucleosides in vivo.
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Hurley, M., Lin, B. & Fox, I. REGULATION OF DEOXYADENOSINE AND NUCLEOSIDE ANALOG PHOSPHORYLATION BY HUMAN ADENOSINE KINASE: 89. Pediatr Res 19, 758 (1985). https://doi.org/10.1203/00006450-198507000-00109
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DOI: https://doi.org/10.1203/00006450-198507000-00109