Understanding antagonist/agonist drugs

[GomerPyle]

Hello! I just have a quick question regarding drugs/enzyme's that bind to sites of receptors. So if an enzyme that mimics a protein that binds to a receptor, does it activate or deactivate the receptor? If it binds directly to it, doesn't it always activate it because in order for it to bind, it must have the same shape as the original protein that usually binds to it, so wouldn't the receptor always produce the same response? How would you know if it inhibits or activates?

I am having a brain fart - so much cramming these last few days.

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[AureatEagle]

Hello! I just have a quick question regarding drugs/enzyme's that bind to sites of receptors. So if an enzyme that mimics a protein that binds to a receptor, does it activate or deactivate the receptor? If it binds directly to it, doesn't it always activate it because in order for it to bind, it must have the same shape as the original protein that usually binds to it, so wouldn't the receptor always produce the same response? How would you know if it inhibits or activates?

I am having a brain fart - so much cramming these last few days.

It could potentially be both. A third party substrate that binds directly to the receptor could have either antagonistic or agonist behavior depending on its structure. Some substrates, for example, are able to bind to the receptor because they have sufficient affinity for it, but they can fail to activate the receptor due to insufficient efficacy (in other words, similar enough shape to bind, but they might have a missing or mutated component required for triggering activity, for example). In this case, the third party substrate would be an antagonist because it doesn't activate the receptor, and is acting as a competitive inhibitor for agonist activity.

Other substrates, however, could potentially have enough affinity AND efficacy to trigger agonist activity by having sufficient similarity to the normal substrate. These would be considered agonists.

 

[catzzz88]

Hello! I just have a quick question regarding drugs/enzyme's that bind to sites of receptors. So if an enzyme that mimics a protein that binds to a receptor, does it activate or deactivate the receptor? If it binds directly to it, doesn't it always activate it because in order for it to bind, it must have the same shape as the original protein that usually binds to it, so wouldn't the receptor always produce the same response? How would you know if it inhibits or activates?

I am having a brain fart - so much cramming these last few days.

It can do both!

Look at structures for dopamine, epinephrine, and norepinephrine. They look pretty similar, right? Well, it turns out that they each have their own highly specific receptors. But, surprise, surprise... they also have affinity for each other's receptors (just not as strong). In this case, they are considered agonists because they bind AND activate the receptors (even if it is not technically supposed to be their receptor).

Receptor antagonists can be thought of in exactly the same way as enzymatic inhibitors (its the same thing). Antagonists can be competitive or non-competitive and all they do is bind a protein (whether its a surface receptor or a cytoplasmic enzyme) and prevent the true substrate from using the enzyme appropriately.

You are NOT supposed to be able to look at the shape of a compound and be able to tell whether it is an antagonist or agonist. They will give you the relevant information to be able to figure that out. Here is an example of a dopamine antagonist.

However, in general, if they did give you a question asking about something "mimicking" a substrate and binding to a receptor/enzyme, you can assume that (lacking any other relevant information) it is an antagonist. I say this only because of the wording. If they said it was a substrate with lower affinity or something like that, it would be different.

Hope this helped.

Best,
C

 

[GomerPyle]

Thanks a bunch guys.

So if an enzyme "mimicks" another enzyme that binds to its usual receptor, doesn't mimicking mean to have the same response? When you are mimicking something, it means to copy it, correct? So how would you assume it is antagonizing rather than agonizing?

 

[catzzz88]

Thanks a bunch guys.

So if an enzyme "mimicks" another enzyme that binds to its usual receptor, doesn't mimicking mean to have the same response? When you are mimicking something, it means to copy it, correct? So how would you assume it is antagonizing rather than agonizing?

If I said that a fly "mimics" a bee, it means it looks and acts quite like a bee, but it is not a bee by action (i.e. it cant actually sting you). In the same way, a "mimic" substrate or molecule is one that closely resembles another molecule, but is not actually equivalent in action (i.e. it cannot act as the substrate it mimics). Thus, a "mimic" would be an antagonist, an inhibitor -- simply because it probably binds to an active site but cannot be altered by the enzyme, thus taking up space and often competitively inhibiting.

Take a look here:
http://www.chem.ucla.edu/harding/IGOC/S/substrate_mimic.html
http://en.wikipedia.org/wiki/Enzyme_inhibitor