Activators and Inhibitors

Regulation of enzyme activity is achieved in a variety of ways, ranging from controls over the amount of enzyme protein produced by the cell to more rapid, reversible interactions of the enzyme with metabolic inhibitors and activators. Chapter 15 is devoted to discussions of enzyme regulation. Because most enzymes are proteins, we can anticipate that the functional attributes of enzymes are due to the remarkable versatility found in protein structures. 

Toxin (Enzyme Inhibition) Biosensors Enzyme affectors (inhibitors and activators) that influence the rate of biocatalytic reactions can also be measured. Sensing probes for organophosphate and carbamate pesticides, for the respiratory... 

In addition to their active sites, these enzymes often have multiple sites for a variety of activators and inhibitors (e.g., AMP, ATP, citrate, fructose-2,6-bisphosphate [F2.6-BP]). Cooperative enzymes are sometimes referred to as allosteric enzymes because of the shape changes that are induced or stabilized by binding substrates, inhibitors, and activators. 

Allosteric inhibitors and activators of rate-limiting enzymes... 

Natural Product Inhibitors and Activators of Histone Deacetylases... 

Figure 10.1 Inhibitors and activators of sirtuins. Inhibitors. 1, sirtinol 2, splitomicin 3, cambinol 4, H R-73 5, EX-527 6, AGK-2 7, tenovin-6 8, nicotinamide. Activators 9, resveratrol 10, SRT-1720 11, isonicotinamide.

Legler has considered two mechanisms for the ion-pair formation between basic inhibitor and active-site carboxyl group162 ... 

Even though most enzyme thermistors have been used for determining substrates, a few applications to the determination of inhibitors and activators, as well as enzyme activities, have also been reported. The enzymes employed for this purpose are usually isolated previously, though some are used in their original tissues and microorganisms [157]. 

C. T. Supuran, D. Vullo, G. Manole, A. Casini, A. Scozzafava (2004). Designing of novel carbonic anhydrase inhibitors and activators. Curr. Med. Chem. Cardiovasc. Hematol. Agents 2 49-68. 

Regulation of Enzyme Activity by Binding of Inhibitor and Activator Proteins... 

Enzyme-specific inhibitor and activator proteins can be considered as a type of effector molecules. 

TCA cycle enzyme synthesizing a-ketoglu-tarate, its products, inhibitors, and activators... 

Most, if not all, milks contain sufficient amounts of lipase to cause rancidity. However, in practice, lipolysis does not occur in milk because the substrate (triglycerides) and enzymes are well partitioned and a multiplicity of factors affect enzyme activity. Unlike most enzymatic reactions, lipolysis takes place at an oil-water interface. This rather unique situation gives rise to variables not ordinarily encountered in enzyme reactions. Factors such as the amount of surface area available, the permeability of the emulsion, the type of glyceride employed, the physical state of the substrate (complete solid, complete liquid, or liquid-solid), and the degree of agitation of the reaction medium must be taken into account for the results to be meaningful. Other variables common to all enzymatic reactions—such as pH, temperature, the presence of inhibitors and activators, the concentration of the enzyme and substrate, light, and the duration of the incubation period—will affect the activity and the subsequent interpretation of the results. 

Binding of a substance to an allosteric site sometimes has the effect of increasing the activity of an enzyme rather than inhibiting it. This may occur because the activator stabilizes the conformation that binds substrate best (Fig. 9-12). The quantitative treatment of such activation is similar to that of inhibition allosteric inhibitors and activators are often considered together and are referred to as modifiers or... 

According to the MWC model, in the presence of inhibitor and activator at normalized concentrations P and y an enzyme will still follow Eq. 9-65, but the allosteric constant L will be replaced by an apparent allosteric constant L (Eq. 9-70).86 Figure 9-14 shows plots of Y vs. log a for two different values of L for a tetramer with a specific value assumed for c. In both... 

The effects of inhibitors and activators on RNases Ti, N1 Ui, U2, and T2 are summarized in Table IV (5, 7, 8), showing the characteristics of each RNase. Ribonuclease Ti is strongly inhibited by 10 3M Zn2+ RNases and T2 are inhibited about half but RNases N and U2 are not inhibited. Ribonuclease T, is also strongly inhibited by 10 3M Ag+, while all other RNases are inhibited about half. But 10 3 M Cu2+ strongly inhibits RNase T2 and only about half inhibits the other RNases. All five RNases are not inhibited by 10 2 M ethylenediaminetetraacetate (EDTA) and 10-3 M ICH2COOH. No metallic cofactor is required for their action. 

The metabolic roles and regulation of glucose-6-P phosphohydrolase activity have been considered in detail in reviews by Cahill et al. (6) and Ashmore and Weber (7). More recently, possible metabolically important roles for phosphotransferase activities of this enzyme in liver, kidney, and intestine have been described in reviews by the present author (9, 10)—who also considered a variety of regulatory features based on interaction of substrates, inhibitors, and activators with the multifunctional enzyme—and by Cohn et al. (11). 

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