Modelling the effects of inhibitors of guanine nucleotide synthesis: implications for studies of cellular differentiation pathways.
Mizoribine induces the differentiation of promyelocytes by an unknown mechanism that relies on compromised guanine nucleotide synthesis. I have found that mizoribine also perturbs adenosine nucleotide levels in HL-60 promyelocytes, particularly ATP. To reconcile these observations with the known actions of mizoribine I have adapted an existing model of human purine metabolism composed as an S-system familiar from Biochemical Systems Theory. Mizoribine's actions were then simulated and compared with experimental data.
Thomas
Geraint M H
GM
Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK. g.thomas@ucl.ac.uk
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D006150:Guanine Nucleotides / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D012263:Ribonucleosides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006150:Guanine Nucleotides; D012263:Ribonucleosides; C010052:mizoribine; D006160:Guanosine Triphosphate