Competitive inhibition is the inhibition of an enzyme or receptor by so-called antagonists or inhibitors. These are substances that are similar in chemical structure to the endogenous substance intended to bind to the target structure.
What is competitive inhibition?
Competitive inhibition is the inhibition of an enzyme or receptor by so-called antagonists or inhibitors. Various structures in the human anatomy are equipped with binding sites. Such structures include, for example, receptors and enzymes. Usually, different substances are capable of binding to the binding sites of these structures. If multiple substances compete for binding to an anatomical structure, then competitive inhibition of the target structure may be present. Biochemistry and pharmacology know the competing substances as agonist and antagonist. The agonist is a substance to occupy receptors, which activates signal transduction by binding. Agonists are either endogenous substance or artificial imitations of such substances. In pharmacology, antagonists are substances that inhibit the action of an agonist. When a structure is inhibited by the binding competition of agonist and antagonist, competitive inhibition is present. Thus, an agonist and antagonist compete for occupancy of the target structure in competitive inhibition. The antagonist usually has no biochemical effect itself. Noncompetitive inhibition should be distinguished from competitive inhibition, in which the inhibitor does not attach to the active site of the enzyme but binds to another site of the enzyme and in this way achieves a conformational change and inactivation of the enzyme.
Function and task
Agonists occupy specific receptors in the body and thus together with them form complexes with specific effects. Receptors are stimulus-responsive sites in the organism with specific structure for binding to an agonist. The ability to bind to receptors and trigger their action is called intrinsic activity. Antagonists to a particular agonist resemble the agonist in chemical structure and thus occupy the receptors designed for it. However, an antagonist-receptor complex does not exert the effect intended for agonist-receptor binding. Thus, the receptor is inhibited in its action by occupation with an antagonist. The strength of the binding effort between a particular substance and a receptor is called affinity. Antagonists must have a higher binding affinity than the agonist in order to displace an agonist from its receptors. This principle follows the law of mass action. That is, if the binding affinity is the same, displacement of the agonist can still occur if the antagonist is present at a higher concentration. Non-competitive antagonists can be displaced by higher concentration agonists. This principle does not apply to competitive antagonists. The strength of competitive antagonists is the so-called pA2 value and is determined by the Schild plot. Most antagonists in pharmacology are physiological, i.e. endogenous substances. In addition to enzymes, mediators and their antagonists are thus mainly used in drugs today. Histamine, for example, is an inflammation-mediating tissue hormone. It is a physiological agonist that binds to specific histamine receptors and causes redness, swelling and pain in the tissue as a result of the binding. In this case, the physiologically intended effect of the agonist-receptor complex is the inflammatory response. As antagonists to histamine, pharmacology relies on H1 antihistamines. These substances are biochemically extremely similar to histamine and are thus capable of displacing histamine from the receptor. As an antagonist-receptor complex, these antagonists do not exert any effect of their own. Thus, H1 antihistamines can prevent or at least reduce inflammation. In terms of enzymes, medicine refers to an inhibitor as one that competes with the intended substrate for an active site. The enzyme cannot convert the inhibitor and stops working for this reason. Inhibition persists only if the concentration of the inhibitor remains sufficiently high to do so.
Diseases and disorders
Inhibitors based on the principle of competitive inhibition are used to treat a variety of medical conditions.Therapy by competitive inhibition is common, for example, in the treatment of acute gout attacks. The inhibitor NSAID is used to inhibit prostaglandin synthesis. It inhibits cyclooxygenase, an enzyme involved in inflammatory metabolism. This inhibition results in a pain-reducing and anti-inflammatory effect. Conventional agents for acute gout are ibuprofen or diclofenac. In chronic gout, the main inhibitors used are [[uricostatic agents]]. These substances inhibit xanthine oxidase. Xanthine oxidase oxidizes hypoxanthine to xanthine, which eventually becomes uric acid. Thus, inhibition of xanthine oxidase causes uric acid formation to decrease and reduces gout symptoms. At the same time, the administration of the inhibitors increases the concentration of hypoxanthine in the body. Thus, purine synthesis is also inhibited from then on. Competitive inhibition offers a decisive advantage over other inhibition methods. Pharmacologists distinguish between reversible and irreversible inhibition. In irreversible inhibition, an irreversible inhibition process is present. The process cannot be reversed even by a more highly concentrated agonist. In reversible inhibition, on the other hand, reversibility is present. Competitive inhibition can therefore be reversed in most cases by increasing the agonist concentration. This type of inhibition is therefore one of the most important mechanisms of action for drugs. However, the mechanism of inhibition by inhibitors is not exclusively associated with therapies and therapeutic success. For example, inhibition also plays a role in the pathogenesis of cancer. Tumor cells release apoptosis inhibitors and thus increase their vitality. They give themselves resistance to immunological therapies and prevent their own cell death.
