Homotropic Cooperativity

The separation between allosteric effectors and cooperativity lies in the molecule doing the affecting. If the effector molecule acts at another site and the effector is not the substrate, the effect is deemed allosteric and heterotropic. If the effector molecule is the substrate itself, the effect is called cooperative and/or homotropic. 

Figure 8.15. Bis for the model of Section 8.8, with parameters given in Eq. (8.8.10), and m = 10. The curves from left to right correspond to increasing values of Xg = 0,5,10,15,..., 40. Note the transition from the noncooperative BI for = 0 to a highly (positive and homotropic) cooperative curve for...

The symmetry model (fig. 2.4) of allostery can describe the cooperative binding of substrate to enzyme (homotropic effect), as well as the influence of effector molecules on the activity of enzymes (heterotropic effect). 

Homotropic allosteric enzymes generally are multisubunit proteins and, as noted earlier, the same binding site on each subunit functions as both the active site and the regulatory site. Most commonly, the substrate acts as a positive modulator (an activator), because the subunits act cooperatively the binding of one molecule... 

The enzyme from B. stearothermophilus is an a4 tetramer of subunit Mr 33 900. Early kinetic studies indicated that the enzyme acts in a manner that is qualitatively consistent with an MWC two-state model. The enzyme acts as a A system i.e., both states have the same value of kcal but different affinities for the principle substrate. In the absence of ligands, the enzyme exists in the T state that binds fructose 6-phosphate more poorly than does the R state. In the absence of ADP, the binding of fructose 6-phosphate is highly cooperative, and h = 3.8. The positive homotropic interactions are lowered on the addition of the allosteric effector ADP, with h dropping to 1.4 at 0.8-mM ADP.52 ADP thus binds preferentially to the R state. The allosteric inhibitor phosphoenolpyruvate binds preferentially to the T... 

Cupp-Vickery J, Anderson R, Hatziris Z. Crystal structures of ligand complexes of P450eryL exhibiting homotropic cooperativity. Proc Natl Acad Sci USA 2000 97 3050-3055. 

Figures 5.11A and B show the characteristic sigmoid curves obtained as a result of interaction between the substrate site, the stimulating modulator site, and the inhibitory modulator site for K and M classes of enzymes. The curves in the absence of modulators are homotropic effects caused by cooperative binding of the substrate. Heterotropic modulators, which can be either positive or negative in their actions, are molecules other than the substrate.

Homotropic this is where the sites are identical, and each sites is allosteric to the others. This is like the cooperative interactions seen in oxygen binding by haemoglobin - four (essentially) identical oxygen binding sites interacting with each other allosterically. 

Figure 2.12 Plot of F1/2 for Hb as a function of imidazole concentration that illustrates the influence of homotropic effector equilibrium reaction 14 on the ease of reduetion and level of cooperativity (inset). Parameters obtained by spectroelectrochemistry max is defined in Figure 2.4. Conditions Pt mesh electrode [heme] = 0.1-0.23 mM [Ru(NH3)6Cl3] = 0.30-1.1 mM [NaN03] = 200mM [MOPS] = 50 mM at pH 7.1 20 °C. Figure adapted from ref. 11 and used with permission.

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