Homotropic effects

In the Monod-Wyman-Changeux model for allosteric regulation, what values of L and relative affinities of R and T for A will lead activator A to exhibit positive homotropic effects (That is, under what conditions will the binding of A enhance further A-binding, in the same manner that S-binding shows positive coop-... 

It was pointed out in Section 6.8 that the term allosteric as coined by MCJ and MWC has been used with three different meanings. In Chapter 6 we discussed the allosteric effect in hemoglobin (Hb). There, the two allosteric sites were identical this has been referred to as the homotropic effect. When the two sites bind different ligands, the heterotropic effect, the induced fit by one ligand can either enhance or diminish the binding affinity of the second ligand (see the example in Section 4.5). 

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). 

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.

The Model of Monod, Wyman, and Changeux (MWC Model) for Homotropic Effects... 

The MWC model of the previous section accounts only for homotropic effects, as occur, for example, with 02 binding to hemoglobin, but heterotropic effects are frequently observed with regulatory enzymes. To incorporate these effects into the MWC model, we must introduce the binding... 

Relationship between the initial velocity (v) and the substrate concentration [S] for an allosteric enzyme that shows a homotropic effect. The substrate functions as a positive modulator. The profile is sigmoidal, and during the steep part of the profile, small changes in [S] can cause large changes in v. Ko.i represents the substrate concentration corresponding to half-maximal velocity. 

Hemoglobin binding of oxygen is a classic example of the homotropic effect. Hemoglobin also shows heterotropic effects with specific molecules in its environment. These effects are intimately related to the function of hemoglobin as a carrier not only of oxygen but of H+ and CO2 (Chapters 1 and 28). The heterotropic modulators are H+, CO2, and... 

A homotropic effect occurs when the binding of one substrate molecule perturbs the rate of catalysis of a second molecule of the same substrate. It is possible for the homotropic effect to be either positive, that is, to give rise to an increased rate of catalysis (homotropic activation, positive cooperativity, or autoactivation), or a negative, that is, causing a decreased rate of catalysis (homotropic inactivation, negative cooperativity, or substrate inhibition). These circumstances cannot be adequately modeled by the simple Michaelis-Menten equation, and neither do direct plots of v... 

Let us first define two terms. Homotropic effects are allosteric interactions that occur when several identical molecules are bound to a protein. The binding of substrate molecules to different sites on an enzyme, such as the binding of aspartate to ATGase, is an example of a homotropic effect. Heterotropic effects are allosteric interactions that occur when different substances (such as inhibitor and substrate) are bound to the protein. In the ATGase reaction, inhibition by GTP and activation by ATP are both heterotropic effects. 

Recall What is a homotropic effect What is a heterotropic effect ... 

Homotropic effect refers to allosteric effects produced by enzyme s own substrate and heterotropic effects are due to metabohtes that are not stmcturaUy related to enzyme s substrates. Positive effects are related to enzyme activation and negative effects to enzyme inhibition. Thus, fmctose-diphosphate is a positive allosteric effector of pymvate kinase. 

Allosteric Effect The binding of a guest at one binding site that is influenced by the binding of a second guest, either the same species (homotropic effect) or a different kind of guest (heterotropic effect), bound elsewhere within the host. 

A biscalix[4]arene host 17 can be applied to homotropic negative cooperativity on alkali metal binding (Figure 1.6). A homotropic positive effect was observed in a multi-binding system 18 which incorporated a porphyrin core and four crown ether moieties (Scheme 1.7). ° An oligopyrrole host 19 for Ag+ ions also shows a homotropic effect on the metal binding (Scheme 1.8). ... 

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