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Enzyme inhibition, inhibitors

Enzyme inhibitors inhibit the action of enzymes either reversibly or irreversibly. Since enzymes are such pervasive, powerful biological catalysts, inhibitors can act as potent drugs. Broadly categorized, enzyme inhibitors may be either irreversible or reversible. [Pg.484]

In the case of competitive inhibition, the equilibrium between the enzyme, E, the inhibitor, 1, and the enzyme-inhibitor complex, El, is described by the equilibrium constant Ki. [Pg.662]

The esters of monofluorophosphoric acid are of great interest because of their cholinesterase inhibiting activity which causes them to be highly toxic nerve gases and also gives them medical activity (see Enzyme inhibitors). The most studied is the bis(l-methylethyl)ester of phosphorofluoridic acid also known as diisopropyl phosphorofluoridate [155-91 DFP (5), and as the ophthalmic ointment or solution Isoflurophate USP. It is used as a... [Pg.227]

He/minthosporium (15). The mode of action is considered to be inhibition of the enzyme NADPH-cytochrome C reductase, which results in the generation of free radicals and/or peroxide derivatives of flavin which oxidize adjacent unsaturated fatty acids to dismpt membrane integrity (16) (see Enzyme inhibitors). [Pg.105]

One approach to combating antibiotic resistance caused by P-lactamase is to inhibit the enzyme (see Enzyme inhibition). Effective combinations of enzyme inhibitors with P-lactam antibiotics such as penicillins or cephalosporins, result in a synergistic response, lowering the minimal inhibitory concentration (MIC) by a factor of four or more for each component. However, inhibition of P-lactamases alone is not sufficient. Pharmacokinetics, stability, ability to penetrate bacteria, cost, and other factors are also important in determining whether an inhibitor is suitable for therapeutic use. Almost any class of P-lactam is capable of producing P-lactamase inhibitors. Several reviews have been pubUshed on P-lactamase inhibitors, detection, and properties (8—15). [Pg.45]

Reversible inhibition is characterized by an equiUbrium between enzyme and inhibitor. Many reversible inhibitors are substrate analogues, and bear a close relationship to the normal substrate. When the inhibitor and the substrate compete for the same site on the enzyme, the inhibition is called competitive inhibition. In addition to the reaction described in equation 1, the competing reaction described in equation 3 proceeds when a competitive inhibitor I is added to the reaction solution. [Pg.288]

Like a noncompetitive inhibitor, an uncompetitive inhibitor does not compete with the substrate since it binds to the enzyme—substrate complex but not to the free enzyme. Uncompetitive inhibition... [Pg.320]

Enzyme inhibitors are classified in several ways. The inhibitor may interact either reversibly or irreversibly with the enzyme. Reversible inhibitors interact with the enzyme through noncovalent association/dissociation reactions. In contrast, irreversible inhibitors usually cause stable, covalent alterations in the enzyme. That is, the consequence of irreversible inhibition is a decrease in the concentration of active enzyme. The kinetics observed are consistent with this interpretation, as we shall see later. [Pg.443]

If the inhibitor combines irreversibly with the enzyme—for example, by covalent attachment—the kinetic pattern seen is like that of noncompetitive inhibition, because the net effect is a loss of active enzyme. Usually, this type of inhibition can be distinguished from the noncompetitive, reversible inhibition case since the reaction of I with E (and/or ES) is not instantaneous. Instead, there is a time-dependent decrease in enzymatic activity as E + I El proceeds, and the rate of this inactivation can be followed. Also, unlike reversible inhibitions, dilution or dialysis of the enzyme inhibitor solution does not dissociate the El complex and restore enzyme activity. [Pg.447]

An important tool for elucidating the steps in the pathway was the use of metabolie inhibitors. Adding an enzyme inhibitor to a cell-free extract caused an accumulation of intermediates in the pathway prior to the point of inhibition (Figure 18.12). Each inhibitor was specific for a particular site in the sequence of metabolic events. As the arsenal of inhibitors was expanded, the individual steps in metabolism were revealed. [Pg.579]

Inhibitors. Many common enzyme inhibitors show little or no effect on the activity of Cypridina luciferase in the luminescence reaction (Tsuji et al., 1974). However, EDTA strongly inhibits the bioluminescence reaction, showing a peculiar relationship between the... [Pg.63]

Nucleophilic addition reactions to A -monoprotected a-amino aldehydes 1 (Table 20) represent the beginning of the worldwide interest in peptide isosteres for the preparation of certain specific enzyme inhibitors (e.g., aspartylproteinase inhibition). Some examples of this reaction type show a relatively low diastereofacial selectivity, especially when the reactions are per-... [Pg.86]

Generally inhibitors are competitive or non-competitive with substrates. In competitive inhibition, the interaction of the enzyme with the substrate and competitive inhibitor instead of the substrate can be analysed with the sequence of reactions taking place as a result, a complex of the enzyme-inhibitor (El) is formed. The reaction sets at equilibrium and the final step shows the product is formed. The enzyme must get free, but the enzyme attached to the inhibitor does not have any chance to dissociate from the El complex. The El formed is not available for conversion of substrate free enzymes are responsible for that conversion. The presence of inhibitor can cause the reaction rate to be slower than the ordinary reaction, in the absence of the inhibitor. The sequence of reaction mechanisms is ... [Pg.106]

In such inhibition, the inhibitor and die substrate can simultaneously bind to the enzyme. The nature of the enzyme-inhibitor-substrate binding has resulted in a ternary complex defined as EIS. The Ks and Kt are identical to the corresponding dissociation constants. It is also assumed that the EIS does not react further and is unable to deliver any product P. The rate equation for non-competitive inhibition, unvAX, is influenced ... [Pg.107]

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. [Pg.131]

In non-competitive inhibition, the substrate (S) and inhibitor (I) have equal potential to bind to the free enzyme (E). The inhibitor forms a ternary complex with enzyme-substrate (ES) whereas the substrate will form another ternary complex with enzyme-inhibitor (El). Since the non-competitive inhibitor had no effect on the binding of substrate to the enzyme, the Km value remained consistent (or unchanged). There are two different ways for the formation of ESI ternary complex this complex would not form the product and therefore was decreased. Non-competitive inhibitor had no effect on substrate binding or the enzyme-substrate affinity, therefore the apparent rate constant (K ) was unchanged.5 A possible reason for product inhibition was because of the nature of 2-ethoxyethanol,... [Pg.134]

ACE inhibitors inhibit the degradation of bradykinin and potentiate the effects of bradykinin by about 50-100-fold. The prevention of bradykinin degradation by ACE inhibitors is particularly protective for the heart. Increased bradykinin levels prevent postischemic reperfusion arrhythmia, delays manifestations of cardiac ischemia, prevents platelet aggregation, and probably also reduces the degree of arteriosclerosis and the development of cardiac hypertrophy. The role of bradykinin and bradykinin-induced NO release for the improvement of cardiac functions by converting enzyme inhibitors has been demonstrated convincingly with use of a specific bradykinin receptor antagonist and inhibitors of NO-synthase. [Pg.10]

Substrate Inhibitor Inhibited enzyme Possible clinical outcome... [Pg.448]

Carbonic anhydrase is an enzyme that produces free hydrogen ions, which are then exchanged for sodium ions in the kidney tubules. Carbonic anhydrase inhibitors inhibit the action of the enzyme carbonic anhydrase This effect results in the excretion of sodium, potassium, bicarbonate, and water. Carbonic anhydrase inhibitors also decrease the production of aqueous humor in the eye, which in turn decreases intraocular pressure (IOP) (ie, the pressure within the eye). [Pg.446]

Figure 4.5 Illustration ofthe concepts of potency that is, it is potent but not very effective. Inhibitor and effectiveness for two enzyme inhibitors. B shows less affinityfortheenzyme (high /<,), but Inhibitor A has a strong affinity for the enzyme it is a much more effective inhibitor when (low ff ), but even when it is maximally bound to maximally bound-that is, it is notvery potent but the enzyme it only achieves partial inhibition - is effective. Figure 4.5 Illustration ofthe concepts of potency that is, it is potent but not very effective. Inhibitor and effectiveness for two enzyme inhibitors. B shows less affinityfortheenzyme (high /<,), but Inhibitor A has a strong affinity for the enzyme it is a much more effective inhibitor when (low ff ), but even when it is maximally bound to maximally bound-that is, it is notvery potent but the enzyme it only achieves partial inhibition - is effective.
Substances that do not target the active site but display inhibition by allosteric mechanisms are associated with a lower risk of unwanted interference with related cellular enzymes. Allosteric inhibition of the viral polymerase is employed in the case of HIV-1 nonnucleosidic RT inhibitors (NNRTl, see chapter by Zimmermann et al., this volume) bind outside the RT active site and act by blocking a conformational change of the enzyme essential for catalysis. A potential disadvantage of targeting regions distant from the active site is that these may be subject to a lower selective pressure for sequence conservation than the active site itself, which can lower the threshold for escape of the virus by mutation. [Pg.11]


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See also in sourсe #XX -- [ Pg.38 , Pg.317 ]




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Enzyme inhibition/inhibitors competitive

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Enzyme inhibition/inhibitors irreversible

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