Heterotropic effector

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-... 

Heterotropic effectors The effector may be different from the substrate, in which case the effect is said to be heterotropic. For example, consider the feedback inhibition shown in Figure 5.17. The enzyme that converts A to B has an allosteric site that binds the end-product, E. If the concentration of E increases (for example, because it is not used as rapidly as it is synthesized), the initial enzyme in the pathway is inhibited. Feedback inhibition provides the cell with a product it needs by regulating the flow of substrate molecules through the pathway that synthesizes that product. [Note Heterotropic effectors are commonly encountered, for example, the glycolytic enzyme phosphofructokinases allosterically inhibited by citrate, which is not a substrate for the enzyme (see p. 97).]... 

Fig. 9-10 Behavior of an MWC allosteric enzyme in the presence of positive and negative heterotropic effectors. The activator term, y, in Eq. (9.62) causes the curve to become more hyperbolic, whereas the inhibitor term (j3) renders it more sigmoidal. The curves were constructed using Eq. (9.62) with L = 1,000 and n - 4.

The product of this reaction, oxaloacetate, can either enter the gluconeogenic pathway (Chap. 11) by way of malate or condense with acetyl-CoA to yield citrate. Pyruvate carboxylase is an allosteric enzyme, and it is activated by the heterotropic effector, acetyl-CoA. Thus, pyruvate in the mitochondria is the substrate for either pyruvate dehydrogenase or pyruvate carboxylase, the activities of which, in turn, are controlled by reactants associated with the citric acid cycle. The interplay among pyruvate dehydrogenase, pyruvate carboxylase, pyruvate, and the citric acid cycle is shown in Fig. 12-9. 

E. Eisenstein, D.W. Markby, and H.K. Schachman. 1990. Heterotropic effectors promote a global conformational change in aspartate transcarbamoylase Biochemistry 29 3724-3731. (PubMed)... 

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. 

Many of the enzymes that display such behaviour also respond to heterotropic effectors [32] i.e. substances that are not obviously related to the substrates an example is the regulation of aspartate transcarbamylase [31] by CTP (inhibitor) and ATP (activator), neither nucleotide being a substrate for this enzyme. 

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