Kinetic characteristics of the inhibition

Table VII. Kinetic Characteristics of the Inhibition of Ferroxidase by the Strongest Metal Ion Inhibitors ...

Several of the problems associated with whole cell bioprocesses are related to the highly effective metabolic control of microbial cells. Because cells are so well regulated, substrate or product inhibition often limits the concentration of desired product that can be achieved. This problem is often difficult to solve because of a poor understanding of the kinetic characteristics of the metabolic pathway leading to the desired product. 

Two additional characteristics of the inhibition of mineral absorption by phenolic acids were observed. The inhibition of both P0 absorption (27) and K+ absorption (31, 32) was reversed when the phenolic acid was removed from the absorption solution. Harper Balke (32) found this reversibility to be dependent upon pH the lower the pH, the less the reversal. Also, kinetic plots of the inhibition of mineral absorption showed that the phenolic acids did not competitively inhibit either P0 (26, 28) or K+ (31) absorption. Rather, ferulic acid inhibited PO -absorption in a noncompetitive (26) or uncompetitive (28) manner and jr-hydroxybenzoic acid inhibited K+ absorption in an uncompetitive manner (31). 

As can be seen, the kinetics of the oxidation of the PP/FGG nanocomposites has features characteristic of the inhibited oxidation of PP the parabolic law of oxidation holds, with the parameter b being approximately the same for all the samples. A significant increase in the induction period is observed at the content of FGG 1.6-3.6 wt % x=140 min for pure PP and x = 152, 310, 390 min at 0.8, 1.6, 3.6 wt% of FGG content respectively. This means that FGG is a very effective inhibitor of the oxidation of PP/FGG nanocomposites. However, at low FGG content (0.8%), the induction period is almost the same as that for pure PP. It makes sense that, under these conditions, carbon particles manifest their ability to initiate the oxidation of PP, as was observed previously in the oxidation of graphite-PP composites [12] and in the oxidation fullerene-PP nanocomposites [16]. 

The kinetic and equilibrium parameters of L-malate, succinate, citrate, and a-oxoglutarate uptake have been determined in mitochondria isolated from respiratory-competent cells grown under conditions of aerobic derepression, aerobic and anaerobic catabolite repression, and inhibition of mitochondrial protein synthesis, and also in mitochondria prepared from a respiratory-deficient cytoplasmic petite strain. The activity and kinetic characteristics of the systems were similar in all cases. It may be concluded that the protein components of these transport systems are coded entirely by nuclear DNA and are synthesized on the cytoplasmic ribosomes. 

In a experiment where the quinone pool was reduced even in presence of O2, by inhibiting the respiratory activity upon addition of KCN ( 210 M), TNBT induces, within 5 min, carotenoTd band shift kinetics characteristics of an inhibited ATP-ase (IG). 

Several kinetic characteristics of mushroom tyrosinase will be examined in this experiment. A spectrophotometric assay of tyrosinase activity will be introduced and applied to the evaluation of substrate specificity, Ku of the natural substrate, 3,4-dihydroxyphenylalanine (L-dopa), and inhibition characteristics. 

Interaction of CarbE with nerve agents follows a kinetic of first order characterized by inhibition of CarbE at the active site serine residue described by a bimolecular rate constant, ki (Maxwell and Brecht, 2001). For noncharged nerve agents (e.g. sarin and soman) the ki of rat serum CarbE was found to be >10 M min whereas cationic substrates (e.g. VX) are converted with poor reactivity (ki < 10" M min ). This specificity is explained by the electrostatic characteristics of the large active site containing only a few cation-II bonding and anionic residues (Maxwell and Brecht, 2001 Satoh and Hosokawa, 2006). 

In general, these molecules base their recognition on a specialized binding site and, similarly to enzymes, they catalyse a large variety of reactions, displaying a similar specificity, stereo specificity, kinetics and competitive inhibition, than their enzyme counterparts [453]. However, the rate of accelerations obtained by transition state stabilization still remains lower than that obtained with enzymes, i.e., 10 -10 fold [454]. In search of improved efficiency and since no stable transition state analogues can reproduce all the characteristics of the transition state analogues, new and more sophisticated alternatives have been developed to elicit catalytic antibodies [455]. These include... 

However, I5g measurements do not provide information about the biochemical characteristics of the enzyme-inhibitor interaction and what specific feature of the interaction may have changed and so caused the resistance. Also, I5g measurements need to be done with pooled tissues of several to many insects, depending on their size. To study the frequency of the resistant target site in a population, measurements must be done in individual insects. This can and has been done in house flies (58. 6J.), an armyworm (59), and plant hoppers and leaf hoppers (62.). Detailed inhibition kinetics studies will reveal if a mutation has occurred (58). A mutation causing the enzyme to have decreased affinity for the inhibitor is most clearly reflected in Kinverse relationship between and kj, kj is smaller in resistant insects with insensitive AChE. This is illustrated in Table 2. 

The inhibition of catalase by cyanide shows none of the characteristics of the azide or hydroxylamine inhibition as is to be expected if cyanide combines with the ferric form. At low peroxide concentrations about 10-3 M the equilibrium constant for the formation of the cyan-catalase complex (Ki) determined from kinetic data using the expression... 

The kinetics of each process are determined by the slower processes (3a) and (3b). These lead to an olefin-type surface intermediate (or its precursor) via a dehydration step requiring two sites for its completion, one to accommodate the olefin-related species and one a water molecule. The requirement for a second, vacant site is characteristic of the model, leading in the case of increasing alcohol pressure to autoinhibition due to decreasing availability of vacant sites. With additional assumptions of (i) Langmuir-type adsorption isotherms for both alcohol and oxygen adsorption, and (ii) the absence of inhibition by product, rate expression (42a) was deduced for acetone formation from alcohol. 

Because of the experimental manifestation of time-dependency and requirement for CYP catalysis, mechanism-based CYP inactivation is often referred to as time-dependent, metabolism-dependent, or preincubation-dependent inhibition. A detailed description of the kinetic characteristics of this type of inhibition has been published (Silverman, 1988) and a simplified kinetic equation is presented in Table 5.1. In cases where CYP activity can be recovered by dialysis, the term quasi-irreversible inhibition has been proposed (Ma et al., 2000). In addition, a time-dependency of CYP inhibition can result from the formation of potent yet reversible metabolites (Ma et al., 2000 Zhao et al., 2002 Zhout et al., 2005). Formation of a metabolite-intermediate (MI) complex has been described as another cause for time-dependent CYP inhibition by many quasi-irreversible inhibitors in this situation the metabolite or intermediate coordinates with the heme-ion thus decreasing the rate of catalysis. 

---