Suicide inhibition

Suicide inhibition, also known as suicide inactivation or mechanism-based inhibition, 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. The inhibitor binds to the active site where it is modified by the enzyme to produce a reactive group that reacts irreversibly to form a stable inhibitor-enzyme complex. This usually uses a prosthetic group or a coenzyme, forming electrophilic alpha and beta unsaturated carbonyl compounds and imines.

Examples

Some clinical examples of suicide inhibitors include:

• Penicillin, which inhibits DD-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.
• 5-fluorouracil acts as a suicide inhibitor of thymidylate synthase during the synthesis of thymine from uridine. This reaction is crucial for the proliferation of cells, particularly those that are rapidly proliferating (such as fast-growing cancer tumors). By inhibiting this step, cells die from a thymineless death because they have no thymine to create more DNA. This is often used in combination with Methotrexate, a potent inhibitor of dihydrofolate reductase enzyme.

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 very few resulting side effects.

This enzyme-related article is a stub. You can help Wikipedia by expanding it.v · Categories: Enzyme inhibitors Enzyme stubs Wikimedia Foundation. 2010. Игры ⚽ Поможем написать курсовую Von der Pahlen (crater) Biologics Look at other dictionaries: Non-competitive inhibition — is a type of enzyme inhibition where the inhibitor reduces the activity of the enzyme, by binding not to the active site on the enzyme, but to a different site.[1] More specifically, it is a special instance of mixed inhibition where the… …   Wikipedia Competitive inhibition — is a form of enzyme inhibition where binding of the inhibitor to the active site on the enzyme prevents binding of the substrate and vice versa. Contents 1 Mechanism 2 Equation 3 Derivation 4 …   Wikipedia Mixed inhibition — refers to a combination of two different types of reversible enzyme inhibition – competitive inhibition and uncompetitive inhibition. The term mixed is used when the inhibitor can bind to either the free enzyme or the enzyme substrate complex. In …   Wikipedia COX-2 inhibitor — COX 2 selective inhibitor is a form of non steroidal anti inflammatory drug (NSAID) that directly targets COX 2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX 2 reduces the risk of peptic ulceration, and is the… …   Wikipedia Enzyme inhibitor — Enzyme inhibitors are molecules that bind to enzymes and decrease their activity. Since blocking an enzyme s activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and… …   Wikipedia Monoamine oxidase inhibitor — MAOI redirects here. For the Easter Island statues, see Moai. Monoamine oxidase Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating… …   Wikipedia Phosphodiesterase inhibitor — A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and… …   Wikipedia Dipeptidyl peptidase-4 inhibitor — DPP 4 inhibitors and GLP 1 Inhibitors of dipeptidyl peptidase 4, also DPP 4 inhibitors or gliptins, are a class of oral hypoglycemics that block DPP 4. They can be used to treat diabetes mellitus type 2. The first agent of the class sitagliptin… …   Wikipedia Disulfiram — Systematic (IUPAC) name 1,1 ,1 ,1 [disulfanediylb …   Wikipedia Nepicastat — IUPAC name 5 (aminomethyl) 1 [(2S) 5,7 difluoro 1,2,3,4 tetrahydronaphthalen 2 yl] 1,3 dihydro 2H imidazole 2 thione …   Wikipedia 18+ © Academic, 2000-2024 Contact us: Technical Support, Advertising Dictionaries export, created on PHP, Joomla, Drupal, WordPress, MODx. Mark and share Search through all dictionaries Translate… Search Internet Share the article and excerpts Direct link … Do a right-click on the link above and select “Copy Link”