Degree of inhibition

Figure 2 Stability of /3-poly(L-malate) measured by its activity to inhibit purified DNA polymerase a of P. polyceph-alum. The relative degree of inhibition is shown (100 rel. units refer to complete inhibition). The DNA polymerase assay was carried out in the presence of 5 /tg/ml /S-poly(L-malate) as described [4]. The polymer was preincubated for 7 days at 4°C in the following buffer solutions (50 mM) KCl/HCl (—A—). Citrate (—V—). 2-(A/-Morpholino)-ethanesulfonic acid, sodium salt (—O—). Sodium phosphate (— —). N-(2-Hydroxyethyl)piperazine-N -(2-ethanesul-fonic acid), sodium salt (— — ). N,N-b s (2-Hydroxyethyl)-glycine, sodium salt (—T—). Tris/HCl (— —). 3-(Cyclo-hexylamino)-l-propanesulfonic acid, sodium salt (— —).

EDTA concentration and the degree of inhibition (Shimomura et al., 1961). In a 30 mM sodium phosphate buffer containing 60 mM NaCl, pH 7.0, inhibition by EDTA is very strong (84%) even at an EDTA concentration as low as 25 pM, but the inhibition does not increase beyond 90% even at an EDTA concentration of 5 mM. The inhibition is completely reversed by the addition of a sufficient amount of Ca2+ to bind EDTA. 

Reversible metabolic inhibition caused by an inhibitor binding to an enzyme site different from the substrate. The degree of inhibition is independent of the substrate concentration. 

Electrophoretic methods of separation of LD Tsoenzymes have become routine in clinical laboratories. Efforts are now being made to standardize the methodologies used for LD isoenzymes, particularly by Rosalki (38). The preferred methods are based on electrophoresis on a solid medium, so that the several bands may be scanned instrumentally. Differential isoenzyme inhibition with urea or other inhibitors is based on the fact that the heart LD isoenzyme is more resistant to inhibition than other isoenzymes. However, the analyst then has the problem of allocating the observed degree of inhibition between the different isoenzymes of a given sample, a problem that has not been resolved satisfactorily thus far. Hence, differential inhibition is not as reliable for isoenzyme separation as is electrophoresis. 

Effect of PG inhibitor concentration on PG activity Various amounts of inhibitor were added in the assay mixture and the degree of inhibition of polygalacturonase activity was measured which showed a linear relationship between inhibitor concentration and percent inhibition... 

In the process of passivation, metals usually are found only in one of the two extreme states, active or passive. The transition between these states occurs suddenly and discontinuously. The intermediate state in region BC can only be realized with special experimental precautions. It is in this sense that passivation differs from the inhibition of electrochemical reactions observed during adsorption of a number of surface-active substances, where the degree of inhibition varies smoothly with the concentration of added material. 

The short time periods (10 min to 4 hr) over which absorption was measured (Table 1) helps support the hypothesis that certain allelochemicals inhibit mineral absorption directly. Under acidic conditions (pH 4.0) salicylic acid inhibited K+ absorption within 1 min (32). The degree of inhibition remained constant over time when salicylic acid inhibited 1C " absorption (32) and when vanillic acid inhibited P0 absorption (28). Thus, at least phenolic acids appear to inhibit absorption rapidly and consistently. 

The hallmark of slow binding inhibition is that the degree of inhibition at a fixed concentration of compound will vary over time, as equilibrium is slowly established between the free and enzyme-bound forms of the compound. Often the establishment of enzyme-inhibitor equilibrium is manifested over the time course of the enzyme activity assay, and this leads to a curvature of the reaction progress curve over a time scale where the uninhibited reaction progress curve is linear. We saw... 

A single enzyme, inositol monophosphatase, leads to loss of the remaining phosphate and the regeneration of free inositol. This enzyme exhibits similar affinities for all five of the equatorial inositol monophosphate hydroxyls. Inositol 2-phosphate, which is not produced in this degra-dative pathway, is a poor substrate, a property that is probably attributable to its axial configuration. The enzyme is inhibited by Li+ in an uncompetitive manner i.e. the degree of inhibition is a function of substrate concentration. The putative link between the ability of Li+ to interfere with phosphoinositide turnover and its therapeutic efficacy in the treatment of bipolar disorders is discussed in Box 20-1 and Chapter 55. It should be noted that unlike most other tissues, brain can synthesize inositol de novo by the action of inositol monophosphate synthase, which cyclizes glucose 6-phosphate to form I(3)P. The enzyme has been localized immunohistochemically to the brain vasculature. 

Although it is often classified as a SNRI, sibutramine (26) is metabolized in vivo to produce metabolites that have varying degrees of inhibition of NE, 5-HT and DA reuptake [83,84]. It has been approved for the control of obesity in the U.S. and many other countries. 

This degree of inhibition correlated with maximal efficacy in preclinical models. Once daily dosing is supported by a half-life of 8-14 h. Using l4C-labeled compound oral bioavailability was found to be 87% [39]. 

As discussed above, the degree of inhibition is indicated by the ratio of k3/k and defines an inhibitor constant (Kj) [Eq. (3.19)], whose value reports the dissociation of the enzyme-inhibitor complex (El) [Eq. (3.20)]. Deriving the equation for competitive inhibition under steady-state conditions leads to Eq. (3.21). Reciprocal plots of 1/v versus 1/5 (Lineweaver-Burk plots) as a function of various inhibitor concentrations readily reveal competitive inhibition and define their characteristic properties (Fig. 3.5). Notice that Vmax does not change. Irrespective of how much competitive inhibitor is present, its effect can be overcome by adding a sufficient amount of substrate, i.e., substrate can be added until Vmax is reached. Also notice that K i does change with inhibitor concentration therefore the Km that is measured in the presence of inhibitor is an apparent Km- The true KM can only be obtained in the absence of inhibitor. 

The extent or degree of inhibition brought about by inhibitor binding can be calculated if K, is known or can be determined experimentally. The Michaelis-Menten equation can be rewritten to include a correction factor 1 + ([I] -f- K ). For the sake of clarity, let the correction factor be represented by < > which will always have a value greater than 1. For Km to increase in the presence of a competitive inhibitor, the correction must be (t>Km, and it follows that Km = K [u. To reduce the Vmax the correction must be Vmax 4 4>, thus = Vmax 4- 4>... 

Page demonstrated in 1992 in a critical analysis [73] that bicyclic /3-lac-tam antibiotics do not exhibit exceptional chemical reactivity. He concluded that neither kinetic nor ground-state effects indicate a significant degree of inhibition of amide resonance in penicillins and cephalosporins [72] [74], Indeed, in comparison to normal amides, the /3-lactam N-atom does not exhibit any enhanced ability to donate its electron pair to either protons or metal ions [75] [76],... 

For example, experimental data might reveal that a novel enzyme inhibitor causes a concentration-dependent increase in Km, with no effect on and with Lineweaver-Burk plots indicative of competitive inhibition. Flowever, even at very high inhibitor concentrations and very low substrate concentrations, it is observed that the degree of inhibition levels off when some 60% of activity still remains. Furthermore, it has been confirmed that only one enzyme is present, and all appropriate blank rates have been accounted for. It is clear that full competitive inhibition cannot account for such observations because complete inhibition can be attained at infinitely high concentrations of a full competitive inhibitor. Thus, it is likely that the inhibitor binds to the enzyme at an allosteric site. 

Binding of a reversible inhibitor to an enzyme is rapidly reversible and thus bound and unbound enzymes are in equilibrium. Binding of the inhibitor can be to the active site, or to a cofactor, or to some other site on the protein leading to allosteric inhibition of enzyme activity. The degree of inhibition caused by a reversible inhibitor is not time-dependent the final level of inhibition is reached almost instantaneously, on addition of inhibitor to an enzyme or enzyme-substrate mixture. 

Salt concentrations of up to 2% have been shown to be ineffective in preventing the growth of Morganella morganii and Klebsiella pneumonia. Higher concentrations of salt (3.5 to 5.5%) could inhibit the histamine production of some histamine-forming bacteria. In one study, the degree of inhibition of bacteria stored for five weeks at 5°C showed a linear relationship with the concentration of salt. 

The acid hydrolysis of alkyl nitrites (Scheme 53) is inhibited by the presence of /I-cyclodextrin (CD) owing to the formation of 1 1 inclusion complexes that are unre-active or much less reactive than the RONO not complexed. The degree of inhibition... 

---