What's the difference between ligands and cofactors?

[raid517]

Hi what's the difference between ligands and cofactors and what are the differences (if any) in their role of allosteric enzyme regulation/modulation?

[CharonY]

Ligand is a more general term refering to a compound that binds to a given enzyme. It could be a substrate, but also have regulatory roles, for instance. A cofactor refers specifically to a compounds that are part of an active enzyme.

[raid517]

Ligand is a more general term refering to a compound that binds to a given enzyme. It could be a substrate, but also have regulatory roles, for instance. A cofactor refers specifically to a compounds that are part of an active enzyme.

 

Still not as clear as I would like. Do you have any examples to highlight the differences? Also do ligands have regulatory roles in the same way cofactors do? Are both, or only one active in allosteric regulation?

[CharonY]

The ligand is an umbrella term for non-covalently bound compounds to enzymes. Based on that, where would you see the difference between those two?

With regards to allosteric regulation, would you care to give an example of how you understand what allosteric regulation is and the precise role of cofactors (especially with regards to the regulatory function)?

 

To give some more context: cofactor is a more specific term (though it is sometimes used in a somewhat loose fashion). Also the terms holo and apo-enzyme are relevant here.

Edited January 5, 2012 by CharonY

[raid517]

The ligand is an umbrella term for non-covalently bound compounds to enzymes. Based on that, where would you see the difference between those two?

With regards to allosteric regulation, would you care to give an example of how you understand what allosteric regulation is and the precise role of cofactors (especially with regards to the regulatory function)?

 

To give some more context: cofactor is a more specific term (though it is sometimes used in a somewhat loose fashion). Also the terms holo and apo-enzyme are relevant here.

 

OK, at a stab on the first question I suspect if ligands are non-covalently bonded molecules, then cofactors are covalently bonded?

 

As for allosteric regulation the limit of what I understand about this can be found on the Wikipedia page about allosteric regulation. I don't really have time to write an essay based on what I read from this, as I'm supposed to be studying for an exam, and this isn't part of it. I just came across it when looking up something else. But the article doesn't make any clear distinction between the role of ligands and cofactors.

 

Really I appreciate that you are trying to get me to think about this, but I just don't know what these distinctions are, so there isn't a lot of point in asking me to guess.

 

Even if it were true that ligands are 'an umbrella term form non-covalently bound compounds to enzymes' where exactly does this leave us?

 

Cofactors as far as I know bind to sites on the enzymes that are not the active site and cause the enzyme to have specificity in their activity in the presence of a given substrate. That is they can induce a conformational change in the enzyme to produce an induced fit mechanism that more tightly binds the enzyme to the substrate. A bit like a hand loosely grasping a ball at first, and then tightly grasping it, after it receives an appropriate signal to do so.

 

But if you read the Wikipedia page on ligands, it implies (or seems to in places) that certain ligands can perform a similar function.

 

To be honest it's all a bit of a muddle in my mind at the moment - and it would be useful if someone could help me separate the muddle out. Allosteric signaling is a mechanism whereby the presence (or lack thereof) of a given cofactor (or ligand?) within a medium can cause enzymes to speed up the rate of reaction (due to the above mechanism), or slow it down as appropriate.

 

But it's entirely possible I am getting several related concepts confused. Some real world examples of where cofactors and ligands differ would be quite helpful I think. Also which of these is the most significant in terms of allosteric signaling and/or regulation?

Edited January 6, 2012 by raid517

[CharonY]

I think I found at least one source for your confusion:

Cofactors as far as I know bind to sites on the enzymes that are not the active site and cause the enzyme to have specificity in their activity in the presence of a given substrate.

 

Cofactors can very well be part of the active site. Metal cofactors, for instance, are often directly responsible for redox-reactions. In fact, the majorities of cofactors that I can think of are part of the active site. Hence, holoenzymes are referred to the whole active enzyme, that contains the apoenzyme as well as any necessary cofactors. Thus allosteric inhibition (or activation) is not the primary role of cofactors.

 

For ligands you have to shift your viewpoint. Ligands essentially to non-covalently bound molecules, that could include substrate, cofactors as well as allosteric inhibitors.

[raid517]

I think I found at least one source for your confusion:

 

 

Cofactors can very well be part of the active site. Metal cofactors, for instance, are often directly responsible for redox-reactions. In fact, the majorities of cofactors that I can think of are part of the active site. Hence, holoenzymes are referred to the whole active enzyme, that contains the apoenzyme as well as any necessary cofactors. Thus allosteric inhibition (or activation) is not the primary role of cofactors.

 

For ligands you have to shift your viewpoint. Ligands essentially to non-covalently bound molecules, that could include substrate, cofactors as well as allosteric inhibitors.

 

Thanks man. That's much clearer now.