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Question about mixed inhibitors (pretty hairy stuff!)

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anondukie

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So as far as I understand in mixed inhibition I can bind to either E or ES. When I binds to E the equilibrium of the E+S --> ES reaction shifts to the left (Le Chatelier's) and Km is increased (less affinity of E for S). However, when I binds to the ES complex, E+S --> ES equilibrium shifts to the right. Therefore, Km decreases (more affinity of E for S).

My question is as follows: In mixed inhibition, how do we know whether the slope Km/Vmax is increasing or decreasing. It is obvious when Km is increasing and Vmax is decreasing (Vmax always decreases) but what happens when Km and Vmax both decrease? How are we expected to know whether the decrease in Km is large enough to offset the decrease in Vmax and result in a decreasing slope?

Also, do mixed inhibitors bind to active or allosteric sites of enzymes? Kaplan states that they bind to allosteric sites but some internet resources claim that this is not the case.

Thanks!
 

twatery

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that right,i think so,thank you
1jY6yOa
 

theonlytycrane

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The mixed inhibitor binds to the allosteric site. This makes sense because if it bound to the active site, there would be no way for it to bind to the ES complex since S would already be in E's active site. In the case where it binds to ES better than E, I believe that Km and vmax decrease at equal proportions so that the slope of Km / vmax will be parallel to the slope without the inhibitor- similar to what you see with uncompetitive inhibition.
 

anondukie

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That does make sense. I'm curious to know whether certain inhibitors are capable of binding to either site depending on the circumstances in question (not really relevant to the MCAT). We could call them "facultative inhibitors" or something similar.

Thanks for the answer!
 

theonlytycrane

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possibly- I don't know enough to rule this out. Though for the context of the MCAT just know that a competitive inhibitor will bind to the active site (E only) while non-competitive (E and ES), uncompetitive (ES only), and mixed inhibitors (E and ES, one with a higher affinity) will bind to the allosteric sites of the enzyme.
 
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