Types of enzyme inhibitors: competitive, noncompetitive, uncompetitive, & mixed inhibition

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the bumbling biochemist

the bumbling biochemist

8 ай бұрын

Enzyme inhibitors: 
* In the presence of an inhibitor, the inherent “goodness” of an enzyme doesn’t change - it still actually has the same constants, KM, kcat (and thus vmax), etc. BUT what we measure may change - so we call what we measure the “apparent” KM (KMapp) & apparent Vmax (Vmaxapp)  
* Irreversible covalent inhibitors 
* Often “mechanism-based,” aka “suicide” inhibitors → take advantage of covalent catalysis mechanisms → enzyme attacks inhibitor just like it would attack a substrate, but the inhibitor has a poor leaving group, so gets stuck on, preventing the enzyme from regenerating 
* There are 4 main types of reversible inhibitors: 
* Competitive 
* Binds E in active site 
* Competes with S for binding site 
* Resembles substrate/TS 
* ↑ apparent KM (KMapp) but doesn’t affect apparent Vmax (Vmaxapp)  
* Noncompetitive (form of mixed) 
* Binds E & ES at allosteric site with equal affinity & prevents conversion from S to P 
* Does not affect KMapp, but ↓ Vmaxapp  
* Uncompetitive 
* Binds ES (but NOT E) at allosteric site & prevents conversion from S to P 
* ↓ KMapp & ↓ Vmaxapp  
* Mixed 
* Binds E & ES at allosteric site with different affinities & prevents conversion from S to P 
* May ↑ or ↓ KMapp, and will ↓ Vmaxapp  

* Competitive:  
* Binds to active site 
* Competes with substrate for binding to active site 
* Binds E only (because its binding spot is already taken in ES!) 
* Can be competed out 
* Remember that each time the enzyme lets go of a substrate or an inhibitor, it then has a chance of picking up a substrate or an inhibitor  
* The relative concentrations of the 2 will determine which it is more likely to bump into first 
* If you have enough of the substrate it can “win”  
* The relative affinities of the 2 will determine how likely it is to stick & stay stuck to what it bumps into 
* You’ll need more substrate to compete out a stronger inhibitor 
* ↑ KMapp but doesn’t affect Vmaxapp (you’ll just take more S to reach it) 
* Typically look like substrate &/or TS 
* Strongest inhibitors will look more like TS because that’s what the enzyme binds tightest 
* Ki is a measure of inhibitor affinity - it’s basically the dissociation constant, Kd, for the inhibitor 
* Lower Ki → stronger affinity 
* Noncompetitive:  
* Binds to an allosteric site (not active site, or at least not in the same spot as the substrate) & prevents conversion of substrate to product 
* Typically will not resemble substrate/TS because it’s binding to a different spot 
* Does not compete with substrate for binding, so cannot be competed out, but can be diluted out 
* If there’s barely any around, the enzyme’s unlikely to find another copy to pick up if it lets go, so if you dilute it a ton, then let it reach equilibrium, there’d basically be none bound 
* Binds E & ES with equal affinity 
* Does not affect KMapp, but ↓ Vmaxapp  
* substrate binding isn’t affected, but the conversion to product is so the apparent affinity won’t change, but the apparent rate of conversion will slow down since those bindings aren’t productive 
* Memory tip: it’s noncompetitive because its binding is basically independent of S binding, so S binding isn’t affected by its presence 
* Uncompetitive:  
* Similarly to noncompetitive… 
* it binds to an allosteric site & prevents conversion of substrate to product 
* Typically will not resemble substrate/TS because it’s binding to a different spot 
* Does not compete with substrate for binding, so cannot be competed out, but can be diluted out 
* But as opposed to noncompetitive, it only binds ES (not E) 
* ↓KMapp & ↓ Vmaxapp  
* substrate binding is increased because binding to ES (forming ESI) draws away ES from the equilibrium binding equation E + S ⇆ ES, leading to a rightward shift (more S binding) thanks to the whole Le Chatlier’s principle thing 
* Memory tip: it’s uncompetitive because it’s binding to basically the “opposite” thing as the substrate, and actually increasing the KMapp, as opposed to a competitive inhibitor, which raises it 
* Mixed inhibition:  
* Really similar to noncompetive, except that it has different affinities for E & ES 
* Noncompetitive is really just an “idealized” form of mixed inhibition that isn’t very realistic 
* Binds E & ES, but with different affinities 
* Can ↓ or ↑ KMapp , but will always ↓ Vmaxapp  
* Will ↑ KMapp if has higher affinity for E (more like competitive except it’s binding to a different site) 
* Will ↓ KMapp if it has higher affinity for ES (more like uncompetitive) 

 blog: bit.ly/enzymeinhibition
 older video with more details: • Enzyme inhibitors: typ...

Пікірлер: 2
@adityaagarwal2341
@adityaagarwal2341 Ай бұрын
I have my entrance tests in 3 days and I wish I found your channel earlier. Love the content❤❤Thank you for the clear and concise explanations
@thebumblingbiochemist
@thebumblingbiochemist Ай бұрын
So happy I could help. Good luck!!!!
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