Abstract
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.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bacon C. W., Sussman A. S., Paul A. G. Identification of a self-inhibitor from spores of Dictyostelium discoideum. J Bacteriol. 1973 Feb;113(2):1061–1063. doi: 10.1128/jb.113.2.1061-1063.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brackenbury R. W., Schindler J., Alexander S., Sussman M. A choice of morphogenetic pathways in Dictyostelium discoideum induced by the adenosine analog formycin B. J Mol Biol. 1974 Dec 15;90(3):529–539. doi: 10.1016/0022-2836(74)90233-2. [DOI] [PubMed] [Google Scholar]
- Ellingson J. S., Telser A., Sussman M. Regulation of functionally related enzymes during alternative developmental programs. Biochim Biophys Acta. 1971 Aug 19;244(2):388–395. doi: 10.1016/0304-4165(71)90241-8. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Newell P. C., Telser A., Sussman M. Alternative developmental pathways determined by environmental conditions in the cellular slime mold Dictyostelium discoideum. J Bacteriol. 1969 Nov;100(2):763–768. doi: 10.1128/jb.100.2.763-768.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sheen M. R., Kim B. K., Parks R. E., Jr Purine nucleoside phosphorylase from human erythrocytes. 3. Inhibition by the inosine analog formycin B of the isolated enzyme and of nucleoside metabolism in intact erythrocytes and sarcoma 180 cells. Mol Pharmacol. 1968 May;4(3):293–299. [PubMed] [Google Scholar]