Competitive Inhibitors (Irreversible) and Km. Mistake in First Aid?

[teehees]

First Aid states states irreversible competitive inhibitors do NOT change the Km

Km is the substrate concentration in which half the active sites are filled.

Increased Km means decreased affinity for substrate and vise versa.

So competitive inhibitors (irreversible) bind to the active site and prevent substrate from filling the active sites. This should result in in an increase in Km right (decreased affinity)?

It should either be increased or just not a valid variable as those sites are never available to bind anymore in the first place to measure it.

Would appreciate some help!

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[CheungBr]

Irreversible binding will not change Km… instead, Vmax will be decreased due to a lesser number of enzymes being available

Hope this helps...

 

[teehees]

why won't it change Km?

The enzyme binding sites are no longer available right? Therefore the affinity (ability to bind substrate) is decreased

 

[CheungBr]

why won't it change Km?

The enzyme binding sites are no longer available right? Therefore the affinity (ability to bind substrate) is decreased

Correct… the binding site is no longer available… therefore, increasing substrate concentration will not relieve the inhibition

In contrast, if a reversible inhibitor was given Km would be increased. Increasing substrate concentration can relieve the inhibition. Vmax would be left unchanged.

 

[teehees]

I don't think you follow. If the binding site is no longer available then that means that the affinity is decreased ie Km is increased.

 

[CheungBr]

I don't think you follow. If the binding site is no longer available then that means that the affinity is decreased ie Km is increased.

If the binding site is no longer available, that enzyme is deactivated. The affinity is neither decreased nor increased.

 

[zhopv10]

CheungBr is correct, irreversible binding you deactivate the enzyme permanently therefore the Vmax is decreased (less enzyme around to do work if you will). Competitive inhibition will alter Km (increase it) and Vmax remains the same. This effectively makes the substrate for the enzyme have a lower affinity. This makes sense because for the substrate to have the effect it had before the inhibitor was added you have to increase concentration to overcome and "win" the competition. Km is the concentration of substrate at 1/2 Vmax and is an intrinsic property of the enzyme. Therefore with irreversible binding you decrease the Vmax because there are less enzymes but you haven't changed the intrinsic affinity that the substrate has for those enzymes that remain (so the slope of the graph is the same). Now with competitive again since you need more substrate for a given effect the concentration of substrate needed to achieve 1/2 Vmax is increased thus you have altered Km. Try drawing out the graphs I think that will help. Hope this helps


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[Kazaki]

I don't think you follow. If the binding site is no longer available then that means that the affinity is decreased ie Km is increased.

I don't think you understand what affinity is...

 

[teehees]

Thanks everyone for your input

Yes sorry I misused the word affinity. I see how if Km is defined by affinity (kind of an intrinsic property) it would remain unchanged. I guess the definition of Kmax that I just read on usmleRx through me off "Km is the substrate concentration in which half the active sites are filled." Which I can see now is crappy but a proper one would need to include alot of details