Inhibition constant

Inhibitors are characterized by inhibition constants which are defined as the ratio of the rate constant for transfer to inhibitor to the propagation constant for the monomer in analogy with Eq. (6.87) for chain transfer constants. For styrene at 50°C the inhibition constant of p-benzoquinone is 518, and that for O2 is 1.5 X 10. The Polymer Handbook (Ref. 3) is an excellent source for these and most other rate constants discussed in this chapter. 

Unlike aniracetam, pramiracetam does not appear to interact with dopaminergic, serotonergic, or adrenergic neurotransmission (72). The agent inhibits prolylendopeptidase in certain brain areas, but its inhibition constant, iC, is only 11 ]lM (69). The absence or weak activity of this compound with various neuronal systems appears to make it less likely to be of significant therapeutic value than other members of this class of agents. 

An adjacent tnfluoromethyl group sharply increases the electrophilic character of the carbonyl carbon Compounds that readily form hydrates and hemiacetals show a time-dependent reversible mhibition of the en yme acetylcholinesterase (equation 2), in which the tight complex makes inhibition only partially reversible [75] In comparison with a nonfluormated analogue, several aliphatic ketones flanked by CFj and CF2 groups, are exceptionally potent reversible inhibitors of acetylcholinesterase, as documented by companson of inhibition constants shown in equation 3 [16 ... 

The pH dependence of HIV-1 protease has been assessed by measuring the apparent inhibition constant for a synthetic substrate analog (b). The data are consistent with the catalytic involvement of ionizable groups with pK values of 3.3 and 5.3. Maximal enzymatic activity occurs in the pH range between these two values. On the basis of the accumulated kinetic and structural data on HIV-1 protease, these pK values have been ascribed to the... 

Cheng, Y. C., andPrasoff, W. H. (1973). Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 percent inhibition (150) of an enzymatic reaction. Biochem. Pharmacol. 22 3099—3108. 

Substrate and product inhibitions analyses involved considerations of competitive, uncompetitive, non-competitive and mixed inhibition models. The kinetic studies of the enantiomeric hydrolysis reaction in the membrane reactor included inhibition effects by substrate (ibuprofen ester) and product (2-ethoxyethanol) while varying substrate concentration (5-50 mmol-I ). The initial reaction rate obtained from experimental data was used in the primary (Hanes-Woolf plot) and secondary plots (1/Vmax versus inhibitor concentration), which gave estimates of substrate inhibition (K[s) and product inhibition constants (A jp). The inhibitor constant (K[s or K[v) is a measure of enzyme-inhibitor affinity. It is the dissociation constant of the enzyme-inhibitor complex. 

In the case of dmg interactions involving metabolic inhibition, little increase in the substrate concentration is expected when the inhibition constant (K ) determined in in vitro studies using human liver samples is larger than the inhibitor concentration in vivo. Various approaches have been adopted using mathematical models in attempts to quantitatively predict in vivo dmg interactions from in vitro data [5]. 

Common inhibitors include stable radicals (Section 5.3.1), oxygen (5.3.2), certain monomers (5.3.3), phenols (5.3.4), quinones (5.3.5), phenothiazine (5.3.6), nitro and nitroso-compounds (5.3.7) and certain transition metal salts (5.3.8). Some inhibition constants (kjkp) are provided in Table 5.6. Absolute rate constants (kj) for the reactions of these species with simple carbon-centered radicals arc summarized in Tabic 5.7. 

Tabic 5.6 Inhibition constants (kr/kv,60 °C, bulk) for Various Inhibitors with Some Common Monomers"... 

The temperature dependence of enz5anatic reactions is modeled with an Arrhenius form for the main rate constant k . The practical range of operating temperatures is usually small, but the activation energies can be quite large. Temperature dependence of the inhibition constants can usually be ignored. 

Results of inhibition studies with nojirimycin and its analogs published up to 1988, and additional data from the author s laboratory, are summarized in Table VI. It should be noted that the inhibition constants are given in pM instead of mM (as in Tables II - V). Data for glycosylamines are included, in order to facilitate an estimation of the effects caused by the different positions of the basic group in the two types of basic sugar derivative. Not included are the data of Reese and coworkers and of Grover and Cushley on nojirimycin, because these authors were apparently unaware of the slow and only partial dissociation of the nojirimycin hydrogensulfite adduct which had been used instead of free nojirimycin. 

Inhibition of D-Glycosida es by Glycon-related Polyhydroxypyrrolidines, Expressed by the Inhibition Constants K in iiM (Adapted from Ref. 97)... 

Double reciprocal plots distinguish between competitive and noncompetitive inhibitors and simpbfy evaluation of inhibition constants Aj. v, is determined at several substrate concentrations both in the presence and in the absence of inhibitor. For classic competitive inhibition, the lines that connect the experimental data points meet at they axis (Figure 8-9). Since they intercept is equal to IIV, this pattern indicates that wben 1/[S] approaches 0, Vj is independent of the presence of inhibitor. Note, however, that the intercept on the X axis does vary with inhibitor concentration—and that since is smaller than HK, (the apparent... 

In the first group of studies, involving kinetic inhibition studies, comparisons of the uilibrium (K ), phosphorylation (IC), and inhibition constant (K.) for the inhibition of electric eel and human erythrocyte AChE by ANTX-A(S) and DFP were done (Table II). From Table II it is seen that ANTX- A(S) has a higher affinity for human erythrocyte AChE (K =0.253 fiM) than electric eel AChE (K j=3.67 aM). AN DC-A(S) also shows greater affinity for AChE than DFP (K =300 fiM). And finally the bimolecular rate constant, Kj, which indicates the overall rate of reaction, shows AChE is more sensitive toward inhibition by ANTX-A(S) (Kj=1.36 pM- min- ) than DFP (K, = 0.033 /iM- min ). These studies add information to the comparative activity of ANTX-A(S) and other irreversible AChE inhibitors but do not show the site of inhibition. 

K. = inhibition constant in units of toxin concentration which... 

Table III. Inhibition Constants for Derivative Brevetoxins Derived from the Cheng-Pmsotf Equation ...

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