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small molecules that interfere with catalysis, slowing, or halting enzymatic reactions
inhibitors
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3 types of inhibition
- 1) reversible, competitive
- 2) reversible, noncompetitive
- 3) irreversible
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Line-Weaver Burk plot
1/(Michaelis-Menten)
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binding/association constant
K a= 
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dissociation constant
K d= 
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stronger binding -> ___ [ES] -> higher ___; lower ____
increased; Ka; Kd
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[S]=Kd
half of the enzyme binding sites are occupied by the substrate
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involves inhibitor binding at an enzyme's substrate binding (active) site
competitive inhibition
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a substance that directly competes with a normal substrate for the enzyme's binding site
competitive inhibitor
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type of inhibitor that resembles normal substrate
competitive inhibitor
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particularly effective inhibitors, bc they bind stronger to the enzyme rather than the substrate
transition state analogs
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products of enzymatic reactions
may accumulate and compete with substrates for binding to the enzyme
(cell activity control mechanism)
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type of inhibition that reduces the concentration of free enzyme
competitive inhibition
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a function of the inhibitor's concentration and its affinity for the enzyme
factor by which [S] must be increased to overcome a competitive inhibitor
1+ [I]/KI
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how does the degree of competitive inhibition vary?
by the fraction of enzyme that has bound inhibitor
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does the inhibitor affect the enzyme's turnover number?
NO
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how does  affect a double reciprocal plot in competitive inhibition?
- changes the slope
- doesn't change the y-intersect
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what competes with methanol for binding to alcohol dehydrogenase?
ethanol
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what do HIV protease inhibitors do?
bind to the active site and mimic the tetrahedral transition state
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disease involving elevated concentrations of uric acid in the blood and tissues, and underexcretion of urine
gout
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target for treating gout
inhibition of the conversion of purines to uric acid by xanthine oxidase
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type of inhibitor that binds to the enzyme-substrate complex, but not at the substrate binding site
uncompetitive inhibitor
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upon binding, this inhibitor induces a conformational change which makes the enzyme inactive
uncompetitive inhibition
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do uncompetitive inhibitors need to resemble the substrate?
NO
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for uncompetitive inhibition: ____ Vmax; ____ Km
lower; same
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how does ' change the double-reciprocal plot during uncompetitive inhibition?
unchanged slope; changed y-intercept
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mixed inhibition
involves inhibitor binding to both the free enzyme and the enzyme-substrate complex
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how does change the double-reciprocal plot during mixed inhibition?
both slope and y-intercept change
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irreversible inhibitor
- bind covalently to the enzyme, or
- destroy a functional group that is required for the enzyme's activity, or
- form a highly stable non-covalent association
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mechanism by which penicillin interferes with the synthesis of peptidoglycan
attacks the key Ser residue in the active site of transpeptidase, generating a very stable covalent adduct, and making the enzyme inactive
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fluorouracil
- creates dead-end covalent complex with thymidylate synthase
- cancer drug
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