Does enzyme inhibitor change ΔG?

[Fish419]

Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) phosphorylates phosphatidylinositol (4,5)-bisphosphate (or PIP2) to generate the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3). The morpholine-containing chemical LY294002 is cell permeable and is a competitive inhibitor of ATP binding PI3K. Each of the following is true EXCEPT:

A. LY294002 can simply diffuse into the cell across the plasma membrane, and increases the Km for the PI3K phosphorylation reaction.

B. LY294002 and adenosine triphosphate bind the same pocket of PI3K and must therefore have some structural similarities.

C. LY294002 likely undergoes simple diffusion to enter the cell and will decrease the Vmax but not change the Km for the PI3K phosphorylation reaction.

D. LY294002 binds the ATP binding domain of PI3K and increases the ΔG of the phospholipid phosphorylation reaction.

The answer they provided is C and in the explanation they said "inhibitors make reactions less likely to happen, thus ΔG for the reaction is likely to increase"
I cannot understand this part, because I think ΔG=-RTInKeq, or ΔG=ΔH-TΔS. Enzyme inhibitor does not change any parameter in those two equations. Plus, since enzyme cannot change ΔG, how can its inhibitor change it?
Any suggestions? Thanks!

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[yeasureyoubetcha]

Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) phosphorylates phosphatidylinositol (4,5)-bisphosphate (or PIP2) to generate the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3). The morpholine-containing chemical LY294002 is cell permeable and is a competitive inhibitor of ATP binding PI3K. Each of the following is true EXCEPT:

A. LY294002 can simply diffuse into the cell across the plasma membrane, and increases the Km for the PI3K phosphorylation reaction.

B. LY294002 and adenosine triphosphate bind the same pocket of PI3K and must therefore have some structural similarities.

C. LY294002 likely undergoes simple diffusion to enter the cell and will decrease the Vmax but not change the Km for the PI3K phosphorylation reaction.

D. LY294002 binds the ATP binding domain of PI3K and increases the ΔG of the phospholipid phosphorylation reaction.

The answer they provided is C and in the explanation they said "inhibitors make reactions less likely to happen, thus ΔG for the reaction is likely to increase"
I cannot understand this part, because I think ΔG=-RTInKeq, or ΔG=ΔH-TΔS. Enzyme inhibitor does not change any parameter in those two equations. Plus, since enzyme cannot change ΔG, how can its inhibitor change it?
Any suggestions? Thanks!

Enzyme inhibitors change kinetics not thermodynamics. A drug that inhibits something wont prevent the rxn from happening. It can slow it down by forcing the enzyme to compete for substrate or binding and effectively remove functional enzyme. Drugs have on/off rates so they don't always stay bound. They're sometimes transient associations but with some you can get really tight binders with sub-picomolar affinities.

 

[Fish419]

Enzyme inhibitors change kinetics not thermodynamics. A drug that inhibits something wont prevent the rxn from happening. It can slow it down by forcing the enzyme to compete for substrate or binding and effectively remove functional enzyme. Drugs have on/off rates so they don't always stay bound. They're sometimes transient associations but with some you can get really tight binders with sub-picomolar affinities.

Thank you. That is what I thought. Then both C and D are not true. Why the answer chooses C?

 

[aldol16]

Are you sure they're not talking about delta G double dagger? Because that's activation energy whereas delta G is simply the free energy change of the reaction.

 

[Fish419]

Are you sure they're not talking about delta G double dagger? Because that's activation energy whereas delta G is simply the free energy change of the reaction.

Great point! Thank you! I will go back and check