Control of Enzyme Catalytic Activity by Effectors

The enzymatic activity is increased/decreased in the presence of an activator/inhibitor, which is the simplest form of controlling catalytic activity of enzymes. Enzyme activa-tion/inhibition is the kinetic effect. Their combined effects may give rise in various forms of metabolic regulations and provoke different explanations, some of which are considered here. 

1 Biochemical oscillation. The availability or dynamic flux of substrates/cofactors may also cause fluctuation in the operational enzyme activities. For example, the coordinated regulation by the coupled effect of metabolites acting as activators and inhibitors gives rise to the periodic response (cyclic fluctuation) of the product or measurable intermediates known as oscillatory effect (Chance et al, 1973). Biochemical oscillation or biorhythmicity is also observed in the signal transduction systems (Myer and Stryer, 1988 Berridge, 1990). The necessary conditions for oscillations can be stated as  

3 Feedback control. The binding of metaboUtes, i.e. substrates/products or effectors to enzymes is an important mode of regulation. Feedback inhibition (negative feedback control) is an important example, in which the first committed step in a biosynthetic pathway is inhibited by the ultimate end product of the pathway (Stadtman, 1966). Table 11.14 summarizes different modes of negative feedback controls that have been evolved to accommodate the regulation of divergent metabolic pathways. 

Some effectors may act as antagonists to feedback inhibition such as reversal of the inhibitory effect of CTP on apartate transcarbamylase by ATP. In some cases, enzymes are activated by metabolites in the precursor substrate activation when an enzyme catalyzing a key metabolic step is activated by a precursor metabolite. For example, Saknibekka typhimurium phosphoenolpymvate carboxylase is activated by fructose-l,6-iiJiphosphate. 

According to the synunetry model (Monad et al, 1965), an oligomeric allosteric enzyme binds activator A and substrate S to its relax state (R state) and inhibitor I to only the tight state (T state). The fractional satmation for substrate Ys, i.e. the fraction of substrate binding sites occupied is expressed by 

---