Inhibition, Activation, and Deactivation

Reactant molecules cause the substrate inhibition and activation discussed in Section 

These effects and deactivation can also be caused by other molecules and by changes in environmental conditions. 

Reversible inhibition ceases when the inhibiting molecule is removed from the system. The molecules can be eliminated from the feed in a flow system or from a batch reaction by a separation process such as dialysis. Two kinds of reversible inhibition are distinguished. Competitive inhibition occurs when an inhibitor molecule occupies a site before it is occupied by a substrate molecule. The assumed mechanism is 

Noncompetitive inhibition occurs when the inhibiting molecule is adsorbed after the substrate molecule has been absorbed. The assumed mechanism is 

The two forms of inhibition can occur together. Their combined effects are modeled by changing the denominator of the rate equation. For an irreversible first-order reaction, a suitable rate equation is 

Reactant molecules cause the substrate inhibition and activation discussed in Section 12.1.1. These eflects and deactivation can also be caused by other molecules and by changes in environmental conditions. 

Some enzymes require cofactors to activate catalysis. Typical cofactors are metal atoms, ammonia, and small organic molecules that associate with the enzyme and help to structure the catalytic site. To conduct an enz5anatic reaction, the necessary cofactors must be suppUed along with the substrate and the enzyme. In cell metabolism, a variety of these cofactors act in conjunction with inhibitors to control the metabolic rate. 

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The biocatalyst a-chymotrypsin s ability to hydrolyze 20 is inhibited in the presence of copolymer 19a loaded with 0.2 mol% of the triphenyl carbinol units. 47b Photoirradiation of 19a results in heterolytic bond cleavage and the formation of the cationic copolymer 19b. In this polymer structure, the biocatalyzed hydrolysis of 20 is activated (V = 1.0 pM min-1). The polymer-induced photostimulated activation and deactivation of a-chymotrypsin in the different membrane environments correlates with the permeability and transport properties of the substrate 20 through the different structures of the polymer membranes.1471 Flow dialysis experiments showed that the polymer states 17a, 18a, and 19a are nonpermeable to 20, and hence the biocata-lytic functions of the immobilized enzyme are blocked. The polymer structures 17b,... 

Its primary action is inhibiting the release of GH from the pituitary gland. Somatostatin al.so suppresses the release of both insulin and glucagon. It causes a decrease in both cAMP levels and adenylate cyclase activity. It also inhibits calcium ion influx into the pituitary cells and suppresses glucose-induced pancreatic insulin secretion by activating and deactivating potassium ion and calcium ion permeability, respcc-tively. The chemistry. SARs, and potential clinical applications have been reviewed.--- ... 

Enzymatic reactions frequently undergo a phenomenon referred to as substrate inhibition. Here, the reaction rate reaches a maximum and subsequently falls as shown in Eigure 11-lb. Enzymatic reactions can also exhibit substrate activation as depicted by the sigmoidal type rate dependence in Eigure 11-lc. Biochemical reactions are limited by mass transfer where a substrate has to cross cell walls. Enzymatic reactions that depend on temperature are modeled with the Arrhenius equation. Most enzymes deactivate rapidly at temperatures of 50°C-100°C, and deactivation is an irreversible process. 

TBTs also cause inhibition of the P450 of monooxygenases. In fish and in the common whelk, TBT causes conversion of P450s to the inactive P420 form (Pent et al. 1998, Mensink 1997). In fish, inactivation was also found with TPT, and was related to the inhibition of ethoxy resorufin deethylase activity (EROD) activity. In these studies, organotin compounds were found both as substrates and deactivators of the hemeprotein (cf. the interaction of organophosphates with B-type esterases). 

The results for PtSn-BM and PtSn-OM catalysts (Figure 6.15) indicate that the addition of tin substantially improves their stability, almost inhibiting the deactivation processes. In the case of PtSn-OM, no deactivation is observed and only a slight loss in the conversion level is observed in the case of PtSn-BM. Nevertheless, in the latter case, catalyst regeneration in air at 773 K allows the original catalytic phase to be obtained, since it recovers its initial activity and selectivity. 

The potency of zebularine is about 10-fold lower than for the azacytosines [73]. Zebularine also inhibits cytidine deaminase [75] which is involved in nucleoside catabolism and deactivates also for example azacitidine and its desoxy analog [76]. Thus, it increases the concentrations of nucleoside triphosphates for incorporation into DNA, the efficacy of DNA methylation and ultimately the anticancer activity of for example azacitidine [77, 78[. Zebularine is metabolized by aldehyde oxidase and ithasbeen shovm that its activity can be increases if an inhibitor of that enzyme, for example raloxifene is given in combination [79]. One big question about all epigenetic drugs is the origin of the observed selectivity towards cancer cells. For zebularine, it has been shown that much less activation towards triphosphate metabolites that can be incorporated into DNA occurs in normal muscle tissue as compared to cancer tissue [80]. 

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