Guanosine metabolism and regulation of fruiting body construction in dictyostelium discoideum.
A cell aggregate of Dictyostelium discoideum either constructs a fruiting body directly or transforms into a migrating slug and fruits later on in some other locale. In the presence of formycin B, an inosine analog, and in an environment that otherwise favors fruiting, aggregates having reached a relatively late (17 hr) stage of fruit construction abandon that program and transform into migrating slugs. They then revert to the fruiting mode and construct normal fruiting bodies without further interference [Brackenbury et al. (1974) J. Mol. Biol. 90, 529-539]. The data presented here suggest that formycin B exerts its morphogenetic effect by interfering competitively with the metabolism of guanosine. Thus: see article. The recovery from formycin B is thought to result from the ensuing accumulation of guanosine and reversal of the inhibition. In support of this are the following: (1) Formycin B does cause, in vivo, an accumulation of guanosine. Exogenoug guanosine reverses the effect of formycin B, depending on their relative concentrations. (2) Guanosine is phosphorylitically cleaved to guanine and ribose-1-P by purine ribonucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyl transferase, EC 2.4.2.1), present in D. discoideum extracts, and formycin B is a competitive inhibitor or this reaction with a very high affinity for the enzyme. (3) Four other analogs, also competitive inhibitors of this enzyme, produce precisely the same morphogenetic deviation. The concentrations required are consistent with the relative K1 values.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004023:Dictyostelium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D005573:Formycins / Q000494:pharmacology*; D006151:Guanosine / Q000378:metabolism*; D009235:Myxomycetes / Q000378:metabolism*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors
D000903:Antibiotics, Antineoplastic; D005573:Formycins; D006151:Guanosine; D011683:Purine-Nucleoside Phosphorylase