Inhibition of Enzyme Action

Although we have described a few of the types of inhibition of enzyme action, several other types are known, and they have been described mathematically. An introductory book such as this can provide only a survey of the vast field of enzyme kinetics so this important and rapidly growing branch of science carmot be treated frilly here. The introduction provided should be sufficient for the nonspecaalist in the field. 

Cathepsin C is inhibited by excess substrate. Numerous examples of product inhibition of enzyme action are known. Phosphate inhibition of acid phosphomonoesterase activity is well documented (Chersi et al.. 

This refers to the inhibition of enzyme action, which causes the rate of enzyme-catalyzed reactions to decrease. Competitive inhibition occurs when a foreign molecule becomes tightly bound to the active site of an enzyme. 

It is now believed that many of our useful drugs exert their beneficial action by the inhibition of enzyme activity in bacteria. Some bacteria, such as staphylococcus, require for their growth the simple organic compound poraaminobenzoic... 

Inhibitors of the catalytic activities of enzymes provide both pharmacologic agents and research tools for study of the mechanism of enzyme action. Inhibitors can be classified based upon their site of action on the enzyme, on whether or not they chemically modify the enzyme, or on the kinetic parameters they influence. KineticaUy, we distinguish two classes of inhibitors based upon whether raising the substrate concentration does or does not overcome the inhibition. 

Inhibition Effects in Enzyme Catalyzed Reactions. Enzyme catalyzed reactions are often retarded or inhibited by the presence of species that do not participate in the reaction in question as well as by the products of the reaction. In some cases the reactants themselves can act as inhibitors. Inhibition usually results from the formation of various enzyme-inhibitor complexes, a situation that decreases the amount of enzyme available for the normal reaction sequence. The study of inhibition is important in the investigation of enzyme action. By determining what compounds behave as inhibitors and what type of kinetic patterns are followed, it may be possible to draw important conclusions about the mechanism of an enzyme s action or the nature of its active site. 

The presence of some substances may hinder the action of an enzyme. Such substances are known as inhibitors, and in some cases the inhibitor may be a metal. It is not necessary to describe all the ways in which an inhibitor may reduce the activity of an enzyme, but one way is by binding to the substrate. This is known as competitive inhibition, and it applies to cases in which the inhibitor competes with the substrate in binding to the enzyme. In noncompetitive inhibition, the inhibitor binds to the enzyme and alters its structure so it can no longer bind to the substrate. In some instances, certain metal ions function as inhibitors of enzyme action, which can be a cause of the toxicity referred to earlier. 

Lithium(I) ions are small but strongly hydrated and could interfere with Mg(II) biochemistry. However, the favored mode of action is interference with Ca(II) metabolism via inhibition of enzymes in the inositol phosphate pathways (470-472). Inositol phosphates are responsible for mobilizing Ca(II) inside cells in response to external stimnlii. Lithium also stimulates glutamate release presumably via activation of the AT-methyl-D-asparate receptor and leads to Ca(II) entry (473). The increased influx of intracellular Ca(II) may activate phospholipase C and stimulate accumulation of inositol 1,4,5-triphosphate (473). 

Mechanisms of Enzyme Action, Use of Product Inhibition and Other Kinetic Methods in the Study of (Walter). Mechanisms of Organic Electrode Reactions (Elving Pullman). ... 

Sarin Pure sarin is a colorless, odorless, volatile, and highly lethal compound. It inhibits the enzyme action of cholinesterase, causing the production of excessive amounts of acetylcholine, which in turn affects the central nervous system. 

Disinfectants come from various chemical classes, including oxidants, halogens or halogen-releasing agents, alcohols, aldehydes, organic acids, phenols, cationic surfactants (detergents) and formerly also heavy metals. The basic mechanisms of action involve de-naturation of proteins, inhibition of enzymes, or a dehydration. Effects are dependent on concentration and contact time. 

Insulin acts by binding to insulin receptors on cell membrane. The insulin receptor complex is internalized. By phosphorylation and dephosphorylation reactions there is stimulation or inhibition of enzymes involved in metabolic actions of insulin. Second messengers like phosphatidyl inositol glycan and DAG also mediate the action of insulin on metabolic enzymes. 

The primary action is inhibition of enzyme ribonucleoside diphosphate reductase. The drug is specific for S phase of the cell cycle and causes cell to arrest at the Gj-S interface. 

Mechanisms of Enzyme Action, Use of Product Inhibition and Other... 

The action of most enzymes is inhibited by many substances. Inhibition is often specific, and studies of the relationship between inhibitor structure and activity have been important to the development of our concepts of active sites and of complementarity of surfaces of biomolecules. Inhibition of enzymes is also the basis of the action of a very large fraction of important drugs. Inhibition may be reversible or irreversible, the latter leading to permanent inactivation of the enzyme. Often, but not always, irreversible inhibition is preceded by reversible binding of the inhibitor at a complementary site on the enzyme surface. 

Nonsubstrate molecules may interact with enzymes, leading to a decrease in enzymatic activity. The study of enzyme inhibition is of interest because it often reveals information about the mechanism of enzyme action. Also, many toxic substances, including drugs, express their action by enzyme inhibition. 

In 1954, Beaufay and de Duve (27) first suggested a relationship between microsomal phospholipid and glucose-6-phosphatase. They observed a loss of enzymic activity from phospholipid-rich microsomal preparations concomitant with extraction with such organic solvents as butanol or treatment with lecithinase. Various studies were carried out to demonstrate that the latter effect was not produced through inhibition of enzymic activity by accumulated products of the hydrolysis of phospholipids. On the basis of their observations that deoxycholate treatment labilized microsomes to phospholipase action, they concluded that . . . the detergent did not exert its primary effect on the dissociation of phospholipids from microsomal protein, but that it probably disrupted... 

Before leaving the matter of amines, we should examine some of the known simpler ones for their effects upon the circulation, especially as to cardiac action and duration of pressor response. The former is noteworthy, as its absence is a necessary prerequisite of the Hochdruckstoff. Presumably an extended vasospastic action should also be a prerequisite. Prolonged action can be produced in at least four ways (1) by some property inherent in the structure of the molecule of the pressor agent which prevents its rapid destruction in situ or in blood (2) by slow liberation of an effector substance from a larger, more complex molecule or system (3) by inhibition of the action of an enzyme system which inactivates some naturally occurring pressor agent and (4) by continuous production from parent sources. Clear-cut examples are not evident at present, although... 

The current theory on the mode of action of copper compounds is that the copper ion, Cu, is the active component, which is released from the different salts on the leaf surfaces. The copper ions in the presence of CO2 from the air and the organic acids excreted from the plant and/or fungal spores interact together to produce the resultant activity. The copper ions and complex-bound copper are capable of penetrating the spores and lead to the inhibition of enzyme reactions. This can occur by the removal of other important metals from their compounds by chelation and also by blocking or interacting with the sulfhydryl groups of the spore enzymes. 

R.J.P. Williams (1963) in Molecular basis of enzyme action and inhibition (P.A.E. Desnuelle, ed), p. 133, Pergamon Press, Oxford. 

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