Heterotropic responses

When binding of a substrate molecule at an enzyme active site promotes substrate binding at other sites, this is called positive homotropic behavior (one of the allosteric interactions). When this co-operative phenomenon is caused by a compound other than the substrate, the behavior is designated as a positive heterotropic response. Equation (6) explains some of the profile of rate constant vs. detergent concentration. Thus, Piszkiewicz claims that micelle-catalyzed reactions can be conceived as models of allosteric enzymes. A major factor which causes the different kinetic behavior [i.e. (4) vs. (5)] will be the hydrophobic nature of substrate. If a substrate molecule does not perturb the micellar structure extensively, the classical formulation of (4) is derived. On the other hand, the allosteric kinetics of (5) will be found if a hydrophobic substrate molecule can induce micellization. 

Enzyme activity can also be affected by binding of substrate and nonsubstrate Mgands, which can act as activators or inhibitors, at a site other than the active site. These enzymes are called allosteric. These responses can be homotropic or heterotropic. Homotropic responses refer to the allosteric modulation of enzyme activity strictly by substrate molecules heterotropic responses refer to the allosteric modulation of enzyme activity by nonsubstrate molecules or combinations of substrate and nonsubstrate molecules. The allosteric modulation can be positive (activation) or negative (inhibition). Many allosteric enzymes also display cooperativity, making a clear differentiation between allosterism and cooperativity somewhat difficult. 

An allosteric situation where is constant but the apparent changes in response to effectors is termed a V system. In a V system, all v versus S plots are hyperbolic rather than sigmoid (Figure 15.12). The positive heterotropic effector A activates by raising whereas 1, the negative heterotropic effec-... 

What selective advantage does possession of multiple hemoglobin genes provide In fish that possess two types of hemoglobin, one responsive and the other unresponsive to heterotropic ligands, such polymorphism offers a clear advantage. One of the hemoglobins assures the... 

Unlike the midpoint slope (//1/2) of an ideal Nernstian plot, the slope of a non-Nernstian response cannot be interpreted as the number of electrons involved in the oxidation/reduction process. For the Hbs, the n parameter is influenced by site-site heterogeneity and allosteric effects.The n parameter is an indicator of the level of cooperativity that is operative high n values indicate a high level of cooperativity, while low n values indicate reduced cooperativity. The sensitivity of the n parameter to heterotropic effectors may be seen in Figure 2.11. The trend illustrated is consistent with the two-state (R and T) model for Hb. Maximum cooperativity is indicated by the highest values for max (defined in Figure 2.4) as illustrated for Hb o the absence of a heterotropic effector. The T-state is stabilised by heterotropic effectors (data points 1-4), which results in an increase in ease of reduction (increase in 1/2) and a decrease in cooperativity (decrease in max) due to a diminished ease of T R shift as a result of T-state stabilisation. R-state stabilisation occurs in HbCPA and horse Hb (data points 6-9), which is characterised by an increase in ease of oxidation (lower Eijf) and reduced cooperativity as illustrated by diminished max values. 

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