Characteristics of the type of Inhibition
uncompetitive inhibition
no ES complex is formed
substrate mimics
-bind to the active site act as competitive inhibition - does not let the substrate react ex: ibuprofen inhibit prostaglandin synthase acting as an anti-inflammatory drug
Uncompetitive inhibitors
-forms ternary complex -blocks turnover of the substrate to the product -binds to a different site on the enzyme or protein -blocks the proper association of enzyme subunits
mix/noncompetitive inhibition
-it can form a complex with E to form an EI complex or form a complex with ES to form the ESI complex - neither has affinity
Examples if inhibitor design
-mimic the substrate -mimic the inhibitor - irreversibly react with a key enzyme involve in the pathway change the conformation or state of assembly of the enzyme
uncompetitive inhibition
-not possible to overcome the inhibition -vmax cannot be reached by adding more and more substrate - adding more substrate gives inhibitor more ES complex to bind to which gives more opportunity for inhibition
Heaavy metal toxicity
Once heavy metal is bond the sulfhydryl cannot be used for catalysis
combination therapy
combining two inhibitors that target the same pathway
Competitive Inhibitor
compete with substrate for binding to the enzyme
KI
can also be noted as an inhibitory dissociation constant
in competitive inhibition the↑ concentration of substrate
can restore the rate of the rxn
Heavy Metal Toxicity
enzymes with sulfhydryl groups that are needed for catalytic activity form tight bonds with mercury, lead, silver, iron, copper
in competitive inhibition an ↑ concentration
equals ↑ in Km
competetitive inhibitor
forms the EI complex
Irreversible inhibitionn
links covalently and irreversibly with the enzyme ex: aspirin in actylatng a key serine residue in the active site oof cyclooxygenase
nerve agents
react with agents that inhibit acetylcholinesterases used to kill insects parathion, durban
Transition state mimic
resembles the transition state does not complete the reaction appears to be stabilizing
Heavy metal toxicity ex:
syphylis treatment which deactivates the enzyme via treatment with mercury and bismuth
suicide substrate
the enzyme "kills itself" when binding to the inhibitor
Suicide substrate
the enzyme binds to the inhibitor and the inhibitor permanently kills the enzyme
irreversible inhibition
the enzyme is no longer active new enzyme is the only way enzymatic activity can be restored
in competitive inhibition competitive inhibitor
the plot is linear v max doesn't change the slope off the plot ↑ as the inhibitor increases
combination therapy example
trimethylprim and sulfamethoxazole -trimethylprim- targets purine synthesis, pyrimidine synthesis, and synthesis of certain amino acids
uncompetitive inhibition
uncommon inhibitor binds to the ES complex not to the free enzyme forms an ESI complex
Irreversible inhibition
--covalent attachment of the enzyme to the inhibitor - covalent modification to the key residues of the enzyme
Transition state mimic
2' deoxycoformycin ( inhibits adenosine deaminase)
Statins
inhibit HMGCoA reductase lowers cholesterol levels they are reversible
Suicide substrate
inhibitor reactive until the enzyme attempts to use it as an enzyme
Gleevc
inhibits protein kinase production and block proliferation of cancer cells
