Suicide inhibition

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Suicide inhibition, also known as suicide inactivation, is a form of irreversible enzyme inhibition that occurs when an enzyme binds a substrate analogue and forms an irreversible complex with it through a covalent bond during the "normal" catalysis reaction.

[edit] Examples

Some clinical examples of suicide inhibitors include:

• Penicillin, which inhibits transpeptidase from building bacterial cell walls.
• Sulbactam, which prohibits penicillin-resistant strains of bacteria from metabolizing penicillin.
• Allopurinol, which inhibits uric acid production by xanthine oxidase in the treatment of gout.
• AZT (zidovudine) and other chain-terminating nucleoside analogues used to inhibit HIV-1 reverse transcriptase in the treatment of HIV/AIDS.

Eflornithine, one of the drugs used to treat sleeping sickness is a suicide inhibitor of ornithine decarboxylase.

[edit] Rational drug design

Suicide inhibitors are used in what is called "rational drug design" where the aim is to create a novel substrate, based on already known mechanisms and substrates. The main goal of this approach is to create substrates that are unreactive until within that enzyme's active site and at the same time being highly specific. Drugs based on this approach have the advantage of offering very few side effects.

v • d • e Pharmacology: enzyme inhibition Class Competitive inhibition - Uncompetitive inhibition - Non-competitive inhibition - Suicide inhibition - Mixed inhibition Substrate Oxidoreductase (EC 1): Aromatase inhibitors - Lipoxygenase inhibitor - Monoamine oxidase inhibitors Transferase (EC 2): Integrase inhibitor - Kinase inhibitors - Reverse transcriptase inhibitors Hydrolase (EC 3): Acetylcholinesterase inhibitors - Phosphodiesterase inhibitors - Protease inhibitors (ACE inhibitor, Trypsin inhibitor) Lyase (EC 4): Carbonic anhydrase inhibitors