Allosteric enzymes homotropic effects

FIGURE 6-29 Substrate-activity curves for representative allosteric enzymes. Three examples of complex responses of allosteric enzymes to their modulators, (a) The sigmoid curve of a homotropic enzyme, in which the substrate also serves as a positive (stimulatory) modulator, or activator. Note the resemblance to the oxygen-saturation curve of hemoglobin (see Fig. 5-12). (b) The effects of a positive modulator (+) and a negative modulator (—) on an allosteric enzyme in which K0 5 is altered without a change in Zmax. The central curve shows the substrate-activity relationship without a modulator, (c) A less common type of modulation, in which Vmax is altered and /C0.sis nearly constant. 

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. 

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. 

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. 

Homotropic effectors When the substrate itself serves as an effector, the effect is said to be homotropic. Most often, an allosteric substrate functions as a positive effector. In such a case, the presence of a substrate molecule at one site on the enzyme enhances the catalytic properties of the other substrate... 

The allosteric kinetic effects of ATCase are shown in Figure 7-6. The interaction of substrates with the enzyme is cooperative (an example of homotropic cooperativity), as indicated by the sigmoidal shapes of the v versus [S] plots, CTP being an inhibitor and ATP an activator. These modulators compete for the same regulatory site and modulate the affinity of the enzyme for its... 

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