02-29-2012, 08:00 AM
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.
....>Some clinical examples of suicide inhibitors include:
PENICILLIN:which inhibits DD-transpeptidase from building bacterial cell walls.
SUBLACTAM: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.
5-FLUROURACIL: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.
EXEMESTANE :a drug used in the treatment of breast cancer, is an inhibitor of the aromatase enzyme.
....>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.
....>Some clinical examples of suicide inhibitors include:
PENICILLIN:which inhibits DD-transpeptidase from building bacterial cell walls.
SUBLACTAM: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.
5-FLUROURACIL: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.
EXEMESTANE :a drug used in the treatment of breast cancer, is an inhibitor of the aromatase enzyme.