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Enzyme Inhibition

Types of inhibtors Med Chem Ch. 7

Does Rev. Inhibitor under go rxn with active site? No
Rev. inhibition depends on what factors? Binding strength and [Inhibitor]
Rev. inhibitor is likely similar to... substrate, product, or cofactor
For Rev. Inhibitor, increase [substrate] results in... lowering inhibition
Ex. of Rev. Inhibitors Diuretics ACE inhibitors Statins Sulfonamides Protease inhibitors Kinase inhibitors antidepressants
What bonding occurs between Irrev. inhibitor and active site? Covalent
For Irrev. inhibitor, increase[substrate].... does not affect inhibition
Irrev. inhibitor likely similar to... substrate
Ex. of Irrev. inhibitors Nerve gases Penicillins Disulfuram Cephalosporins Proton pump inhibitors Orlistat
Orlistat (anti-obesity drug) inhibits.... pancreatic lipase (digests fats)
Orlistat is a ______ inhibitor Irreversible
Irrev. inhibitor binds to _____ site of enzyme active site
Rev. inhibitor binds to _____ site of enzyme active site
Allo. inhibitor binds to ____ site of enzyme allosteric site
Allo. inhibitor binds rev. or irrev. to enzyme? reversible binding
For Allo. inhibitor, increase [substrate]... does not reverse inhibition
Is Allo. inhibitor similar to substrate? not similar to substrate
How does Allo. inhibitor inhibit enzyme? Binds to allosteric site, alters shape of enzyme (and active site), substrate can't bind
Ex. of Allo. inhibitor 6-Mercaptopurine
6-Mercaptopurine blocks synthesis of ____ and ____ purines and DNA
6-Mercaptopurine used to treat... leukemia
Transition-state inhibitors bind rev or irrev. to enzyme? reversible inhibition
Transition-state inhibitors are similar to... transition state of catalyzed rxn
Transition-state inhibitors bond to ____ site of enzyme active site
Transition-state inhibitors bind more strongly than drugs that mimic ____ or ____ substrate or products
Renin inhibitor blocks synthesis of... angiotensin I & II
Renin inhibitor produces what effect in body? lowers blood pressure (anti-hypertensive)
Ho does Renin inhibitor work? Mimics one -OH binding group and tetrahedral geometry Binds to actives site but has to leaving group
Ex. Tansition-state inhibitors ACE inhibitors Protease inhibitors Statins
Suicide inhibitors bind rev. or irrev. to enzyme? Irreversible binding
Suicide inhibitors bind to ____ site of enzyme active site
Ex. Suicide inhibitors Trifluoroalanine Tienilic Acid
Trifluoroalanine blocks alanine transaminase
Trifluoroalanine similar to... rxn substrate
How does Trifluoroalanine work? has -CF3 (base removes 1 F) group that resembles -CH3 rxn binding group Enzyme Nu covalently binds to -CF2
Tienilic Acid covalently binds to ____ (amino acid) cyctein (-CH2-SH)
Tienilic Acid inhibits _______ enzymes cytochrome P450
Useful Antibacterial targets: ______ and _______ Dihydropteroate synthetase and transpeptidase
Useful Antiviral targets: _____ , ______ and ______ HIV reverse transcriptase , HIV protease and viral DNA polymerase
Useful Anti-inflammatory target: _____ Cyclooxygenase
Usefule Cholesterol-lowering target: _____ HMG-CoA reductase
Useful Antidepressant target: _____ Monoamine oxidase
Useful Anti-cancer targets: _____ , _____ , ______ and _______ , ect. Tyrosine kinase , Dihydrofolate reductase , thymidylate synthase and aromatase
Created by: kristin_leann