9-Beta-D-arabinofuranosyladenine 5'-monophosphate (araAMP) is converted directly to its antivirally active 5'-triphosphate form by 5-phosphoribosyl-1-pyrophosphate (PRPP) synthetase.
The antiherpetic agent 9-beta-D-arabinofuranosyladenine (araA) needs to be phosphorylated to its 5'-triphosphate to be effective as an inhibitor of herpes simplex virus replication. Adenosine kinase and deoxycytidine kinase are assumed to convert araA to its 5'-monophosphate. We now found that araAMP is converted to its 5'-triphosphate through a direct pyrophosphate transfer from 5-phosphoribosyl-1-pyrophosphate (PRPP) by PRPP synthetase. The efficiency of phosphorylation of araAMP to araATP is about 5% of that of AMP, as estimated from their Vmax/Km ratios for PRPP synthetase. AraATP is converted to araAMP by PRPP synthetase at a 4-fold higher Km but similar Vmax as ATP.
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
J
J
Balzarini
E
E
De Clercq
D007700:Kinetics; D012268:Ribose-Phosphate Pyrophosphokinase / Q000378:metabolism*; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives* / Q000378:metabolism*
D001084:Vidarabine Phosphate; C000101:ara-ATP; D012268:Ribose-Phosphate Pyrophosphokinase