Metabolism of 1-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)cytosine (HPMPC) in Human Embryonic Lung Cells

Abstract

The acyclic nucleotide analogue HPMPC is in human embryonic lung cells, cultured in vitro, transformed to its mono- and diphosphates (HPMPCp and HPMPCpp) and HPMPCp-choline; the synthesis of HPMPCp is catalysed by pyrimidine nucleoside monophosphate kinase (EC 2.7.4.14); HPMPCp-choline (analogue of CDP-choline) is formed from HPMPCpp and choline phosphate in the presence of CTP:phosphorylcholine cytidylyltransferase (EC 2.7.7.15). These metabolites persist for a long time in the cellular pool even after HPMPC has been removed from the medium; on the other hand, they efflux to the medium. Neither HPMPC, nor any of its metabolites interfere with intracellular CDP-choline level.