Cooperative behaviour in monomeric enzymes. Change of negative to positive cooperativity by effect of a ligand.
Three steady-state models were analysed to see if they could reproduce the following kinetic characteristics in a monomeric enzyme with two substrates: a) kinetic cooperativity with respect to the first substrate but not to the second; b) modulation of the kinetic cooperativity for the first substrate by the concentration of the second; c) change in the sign of the kinetic cooperativity at very low concentrations of the second substrate. A slow transition model previously proposed for vertebrate "glucokinase" (hexokinase D), model I, (Olavarría et al., 1982) was able to reproduce characteristics a and b, but never c. The "mnemonical" model (Ricard et al., 1974), model II, also reproduced characteristics a and b, and failed to reproduce c. Thus when observations were performed at concentrations of the first substrate around K0.5 it was possible to observe a decrease in the Hill coefficient (h) relative to the decrease in the concentration of the second substrate, but values lower than 1.0 were never obtained. At extremely high substrate concentrations, the second substrated did not affect the cooperativity of the enzyme for the first substrate. Model III was similar to Model I, but it was considered that only the enzyme conformer with the higher affinity for the first substrate was catalytically active. With this model it was possible to change positive cooperativity into negative if the second substrated altered the frequency of the conformational transition.
D001665:Binding Sites; D005941:Glucokinase / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands / Q000378:metabolism; D008956:Models, Chemical
D008024:Ligands; D005941:Glucokinase