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Cooperativity

Created by Ross Firestone.

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  • leaf green style avatar for user Zoë
    Why is it that on the graph plotted at the myoglobin curve is above that of the haemoglobin? In the previous example, the noncooperative curve was below the positively cooperative one. Does that matter? Is it just specific to the proteins used in the example?
    (25 votes)
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    • piceratops ultimate style avatar for user austinjwalker16
      This is because they are 2 different proteins. Yes, if we were talking about the same protein then the positive cooperation curve would be above the non-cooperative curve, but in this situation it's like comparing apples and oranges. As a side note, myoglobin must have a higer affinity, otherwise when hemoglobin reached your muscles it wouldn't be able to give its oxygen to myoglobin.
      (40 votes)
  • blobby green style avatar for user NOAH
    I vote someone re-record these videos in a more understandable format!
    (2 votes)
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  • orange juice squid orange style avatar for user Zach
    at He mentions that E+S <-> ES <-> E+P; is this right. In previous videos he mentions that its E+S <-> ES *-->* E+P. Meaning that once the substrate has been turned into product the amount that should return to substrate in negligible and so we consider this a one-way reaction and not a two-way. This is called the Steady State Assumption. So why does he have a "*<->*" arrow at the ES <-> E+P reaction? Confused
    (4 votes)
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    • starky seedling style avatar for user Erick Welch
      The reason he used "-->" when explaining the Steady State Assumption was that when deriving the Michaelis-Menten you assume that it is only going to go in one way, because of the negligible effect of the reverse reaction. This means that when looking at the equation you can use "-->" to show that you will see the "full" amount of "P" formed, but when looking at how it truly works you use "<-->" to signify that there will be some loss of "P."
      (17 votes)
  • leaf blue style avatar for user Brandon Te
    This guy is talking way too fast. Too much jargon. Can we get someone else to redo these videos please?
    (11 votes)
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  • blobby green style avatar for user Jacob.glazebnik
    These videos more too fast. It's very hard to grasp the material and take notes while the narrator is speeding through.
    (2 votes)
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    • male robot hal style avatar for user Eston C Clare
      You can also reduce the speed of the video to 1/4, 1/2, or 3/4 the original speed. You can do this by clicking on the gear button in the lower right hand portion of the video. You can also do this by pressing the ">" button to speed up and the "<" button to slow it down.
      (15 votes)
  • blobby green style avatar for user meredith harman
    -- Is it ALWAYS the case that an enzyme that only has 1 site to bind substrate will exhibit noncooperative binding?
    (4 votes)
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    • old spice man green style avatar for user jeffrey.milberger
      Yes. To have cooperative binding, there must be empty bind sites and a first bound substrate so the bound substrate can affect the affinity of subsequent substrates (make the empty bind sites more or less favorable to bind to) on that enzyme. When there is only one binding site, the first bound substrate cannot do that, because no more substrates can bind.
      (10 votes)
  • blobby green style avatar for user swimmerlife13
    what is the difference between this and allosteric avtivation
    (3 votes)
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    • piceratops ultimate style avatar for user Iman Baharmand
      Hey there! Great question, I was confused by this prior to asking my biochem professor. The answer is a bit more simple than you might think:

      Cooperativity is when a substrate (bound to the active site) increases the binding of more substrates. Allosteric activation is not the substrate that binds the enzyme.. but rather an effector molecule (also known as regulatory proteins)... these effector molecules are usually not converted into the final product like a substrate would be
      (12 votes)
  • blobby green style avatar for user Stephanie Whiting
    This video goes way too fast (really so does this whole series) and doesn't go in depth enough. He assumes you totally grasp the concept in the first three second and zips on, kind of like the crash course videos. I use Khan because they usually take the time to explain it well.
    (6 votes)
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    • leaf green style avatar for user KP Kelsey
      I personally recommend watching once through without taking notes to make sure you get the concepts before trying to capture. From there, consider taking notes of the summary first and then go back and fill in the gaps from the rest of the vid as necessary.
      (1 vote)
  • male robot hal style avatar for user Camile
    In the summery, you say that 1 protéïn can link more than 1 substrate, but is there an enzyme that is not a protéIn?
    (1 vote)
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  • blobby green style avatar for user NOAH
    Dude! slow down! speeding up doesn't mean you know more, it just means you don't know much!
    (3 votes)
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Video transcript

Voiceover: So, we're gonna talk about Cooperative Binding, which is a very interesting topic when discussing enzyme kinetics. But first let's review the idea that we can divide enzyme catalysis into two steps. First, the binding of substrate to enzyme, and second, the formation of product. In using this idea we can derive the Michaelis Menten equation, which is very useful for quantitatively looking at enzyme kinetics. Also remember that as you increase substrate concentration, the speed of product formation will level off at it's maximum value as shown on this graph. Now the first thing that I want to talk about is that some proteins can bind more than one substrate, and not all enzymes have just one active site. So, E plus S can form ES through what I've called reaction of one, but some enzymes can react with another molecule substrate to form ES two, through what I've called reaction two. And again, to form ES three, through reaction three, and so on. Now, these enzymes can form product at any stage of this process no matter how many molecules of substrate are bound. Now, you would expect the rate of reaction one to be faster than the rate of reaction two. If we're looking at the example of an enzyme with three substrate binding sites, there are three empty sites available for substrate to bind through reaction one, and only two available for reaction two. So, you would expect rate one to be faster. Similarly, rate two would be faster than rate three for the same reason. And the idea is that the active site saturation does not increase with substrate concentration linearly. Now I get that that can be a mouthful so let's look at it graphically. But, we're also gonna show an exception to this rule. So in this first graph, I've plotted substrate concentration against the percent saturation of the enzyme. And as you can see the curve levels off as substrate binding sites become occupied. It becomes difficult to bind more substrate molecules as you have more substrate molecules bound. Next, I'm going to draw a different curve that you also might see in some enzymes and, that's where substrate binding happens more quickly as binding sites become occupied. Substrate binding changes substrate affinity. And we call this Cooperativity. Now with respect to cooperativity, we can define three new ideas: Positively Cooperative Binding occurs when substrate binding increases the enzyme's affinity for subsequent substrate. Negatively Cooperative Binding occurs when substrate binding decreases the enzyme's affinity for subsequent substrate more than you would normally expect. And Non-Cooperative Binding is the same as the first example where substrate binding does not affect the enzymes affinity for substrate molecules. So, let's look at this graphically. If we have a protein with let's say five binding sites, and plot the Fraction Occupied versus the Substrate Concentration, you would come up with three possible curves. The green curve, which takes on a sigmoidal shape, would represent an enzyme with Positive Cooperativity. The blue curve, with a hyperbolic shape, would represent an enzyme with Non-Cooperative Binding. And the red curve would represent an enzyme with Negatively Cooperative Binding. Now remember that the effects of cooperative binding are only seen after some substrate has already bound. Which is why the difference in the fraction occupied between the three curves is much smaller, it's smaller values, like the one-fifth that I've shown here, than it is at the higher values. So, let's look at a specific example of a couple of proteins. So haemoglobin, or Hb, is the oxygen carrying molecule that you find in human blood, and it can bind up to a total of four oxygen molecules, and it exhibits Positively Cooperative Binding. Myoglobin, on the other hand, which is the oxygen carrying molecule that you find in muscle tissue, can only bind one oxygen molecule in total. And since it can only bind one, it must exhibit Non-Cooperative Binding since there's no subsequent substrate to speak of. Now, if we make a graph where we plot the fraction of active sites bound in each of these proteins versus the pressure of oxygen, remember oxygen is our substrate here, and since it's a gas we're gonna use pressure instead of concentration, you can see that the red sigmoidal curve associated with haemoglobin's positive cooperative binding looks different from the blue hyperbolic curve associated with myoglobin's non-cooperative binding. So, what did we learn? Well, first we learned that some proteins can bind more than one equivalent of substrate. And next, we learned that there are three different types of Cooperativity: Positive, Negative, and Non-Cooperative. Finally, we learned about proteins that exhibit two different types of cooperativity, which were the oxygen binding molecules haemoglobin and myoglobin.