Competitive inhibition

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Scheme

In biochemistry and pharmacology, an enzyme inhibition in which an agonist and an antagonist compete for the occupation of a receptor is called competitive inhibition (Latin: competere , to desire something together) , whereby the antagonist has no biochemical effect. The corresponding antagonistic substances are called competitive antagonists.

Mode of action

Agonists are substances that occupy receptors and form complexes with them, which have a certain effect in the body . A receptor is a stimulus-absorbing point in the body that is adapted to the structure of its specific substances according to the lock and key principle . The ability of a substance to have an effect in the body through this mechanism is called intrinsic activity . Antagonists have very similar chemical structures to the respective agonists and can occupy their specific receptors. However, the antagonist-receptor complex has no effect, which means that the effect of the receptor is suppressed.

Competitive inhibition of the effect of an agonist by increasing concentrations of an antagonist (embedded shield plot)

The strength of the bond between a substance and the receptor is called affinity . In order to displace the agonists from their receptors and thus exert the inhibitory effect, antagonists must have a greater affinity or be present in a higher concentration in accordance with the law of mass action . In contrast to non- competitive antagonists , competitive antagonists can also be displaced by agonists in higher concentrations. The potency of a competitive antagonist ( pA 2 value ) can be determined with the help of the Schild plot .

In pharmacy , agonists are often physiological, i.e. H. endogenous substances such as enzymes and mediators and their antagonists in the form of drugs . For example, as an inflammation-mediating tissue hormone , histamine is a physiological agonist, which occupies its specific histamine receptor and produces typical inflammatory characteristics such as e.g. B. causes redness, swelling and pain. H 1 antihistamines are chemically very similar to histamine and displace it from its receptor. They have no effect of their own and thus reduce or prevent the spread of inflammation.

However, synthetically, or in rarer cases biotechnologically, agonists also play a role as pharmaceuticals and / or psychotropic substances . For example , the opioids used as analgesics , antitussives , antidiarrheal or intoxicating drugs bind as agonists to one or more of the opioid receptor subtypes, adrenoreceptor agonists such as clonidine are used to treat arterial hypertension (high blood pressure), supportive during anesthesia and to dampen withdrawal symptoms. 5-HT2A agonists such as LSD , dimethyltryptamine or mescaline are known as classic hallucinogens. In the case of substances used as intoxicating drugs in particular, competitive antagonists such as the opioid antagonist naloxone play an important role in the emergency medical treatment of overdoses.

The incorporation of p- aminobenzoic acid into vital substances by pathogenic bacteria can be prevented by chemically similar sulfonamides, which act as competitive inhibitors of tetrahydrofolate reductase.

literature

  • Jeremy M. Berg, John L. Tymoczko, Lubert Stryer : Biochemistry. 6 edition, Spektrum Akademischer Verlag, Heidelberg 2007. ISBN 978-3-8274-1800-5 .
  • Donald Voet, Judith G. Voet: Biochemistry. 3rd edition, John Wiley & Sons, New York 2004. ISBN 0-471-19350-X .
  • Bruce Alberts , Alexander Johnson, Peter Walter, Julian Lewis, Martin Raff, Keith Roberts: Molecular Biology of the Cell , 5th Edition, Taylor & Francis 2007, ISBN 978-0815341062 .
  • Maximilian von Heyden, Dr. sc. hum. Henrik Jungaberle, Dr. med. Tomislav Majić:

Manual Psychoactive Substances 1st edition, Springer Verlag, Heidelberg 2018. ISBN 978-3642551246