The effects of exogenous glucose, uracil, and inorganic phosphate on differentiation in Dictyostelium discoideum.

The cellular slime mold was exposed to exogenous glucose, uracil, and inorganic phosphate for either 900 or 90 min to determine their effects on the cellular levels of glucose 6-phosphate (glucose-6-P), UDP-glucose, glycogen, trehalose, and cellulose. Glucose, and phosphate to a lesser extent, increase the levels of glucose-6-P and trehalose, whereas glycogen levels are increased only by glucose. Uracil inhibits glucose-6-P and trehalose accumulation, and this inhibition is reversed by glucose or phosphate. Uracil, especially in the presence of glucose, stimulates the accumulation of UDP-glucose and cellulose. In an attempt to understand the dynamics of the biochemical mechanisms underlying these experimental observations, fluxes of the same metabolites were imposed on a kinetic model of this system. The effects of glucose, uracil, and phosphate either singly or in various combinations on the accumulation of glycogen and trehalose can be predicted quantitatively by applying the appropriate external flux(es) of these additives to the model; the predicted effects on glucose-6-P levels are qualitatively consistent with the observations, but are greater in magnitude, suggesting compartmentation of glucose-6-P. Matching the observed and simulated results requires a lower level of additive in the simulated system than in the actual experiment, which is consistent with earlier studies on the cellular permeability of these metabolites.It is concluded that the complex of flux changes induced in the model by the perturbing metabolites may also occur in vivo, and that endogenous glucose availability is a critical variable controlling the rate and cessation of differentiation as well as the relative amounts of the saccharide end products of differentiation.