Uncompetitive Reversible Enzyme Inhibition – Enzyme Inhibitors

by Kevin Ahern, PhD

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    00:00 Okay. Now the last inhibition I wanna do, is a little hard to get your head around and I mainly want to just introduce what it does and the effects of this inhibitor.

    00:12 This inhibitor, this type of inhibition is called uncompetitive. An uncompetitive is somewhere in between the two.

    00:19 An uncompetitively inhibited reaction occurs by a mechanism that you see on the screen.

    00:25 The normal substrate binds to an enzyme as before.

    00:28 But in the case of the uncompetitive inhibitor, it only binds to the ES complex.

    00:35 Now that ES complex is on the way to becoming product and so it's only binding at that point. So the more ES complex we have which is we are gonna have with more substrate. The more ES complex we have the more inhibited enzyme that we have.

    00:52 Now that's kinda hard to get our heads twisted around. We are gonna see, in fact, as we look at the plot that's gonna be difficult to conceptualize as well.

    00:59 Let's take a look at the kinetics now of an uncompetitive reaction compared to that of an uninhibited reaction.

    01:06 Again we are plotting V versus S, as we have done before.

    01:08 The orange plot is the uninhibited reaction, no inhibitor present, and we see a normal hyperbolic plot.

    01:14 When we plot the uncompetitive inhibited reaction; however, we see something that's a little hard to get our heads around.

    01:22 The confusion with the uncompetitive reaction is that, first of all, we see that it has a lower apparent Vmax and it does have a low apparent Vmax.

    01:31 And the other thing that's confusing about this, is it has a slightly higher velocity at lower concentrations.

    01:38 And that happens actually; because, the uncompetitive inhibitor favors the ES complex. It says if we are increasing the percentage of the enzyme present in the ES complex, and that has the affect of apparently speeding up the reactions which is why that first part of the curve, the velocity for the uncompetitive reaction is higher than it is for the reaction with no competitor.

    02:05 Well when we do the plots we also see something interesting that happens and that is that the uncompetitive reaction has a lower Km value.

    02:12 So not only does the uncompetitive reaction at high substrate concentrations have a lower velocity; because, at higher substrate concentration we will have a greater percentage of the enzyme in ES complex which is greater target for the uncompetitive inhibitor.

    02:28 But we also see that the apparent Km of the enzyme is decreased. And again this happens because the the inhibitor is favoring the ES complex. It's making it look like the enzyme is binding substrate better.

    02:41 Well that confusing result is reflected in what we see on a Lineweaver Burk plot.

    02:47 On the Lineweaver Burk plot, what we have is something that looks like this.

    02:53 The green line, again, shows the uninhibited reaction with what we have seen before, that 1/Vmax intercept on y-axis, and the -1/Km on the x-axis.

    03:02 The Lineweaver Burk plot for the uncompetitive reaction shows a value higher on the y-axis for 1/Vmax and that's reflect with the fact that the Vmax has decreased so 1/Vmax has increased.

    03:15 And we also see the x-axis has moved further to the left, meaning -1/Km has further away from 0 which is what happens when we have a lower Km.

    About the Lecture

    The lecture Uncompetitive Reversible Enzyme Inhibition – Enzyme Inhibitors by Kevin Ahern, PhD is from the course Enzymes and Enzyme Kinetics.

    Included Quiz Questions

    1. Inhibitors bind non-covalently only to the ES complex
    2. Inhibitors resemble the natural substrate
    3. Vmax is increased
    4. Km is increased
    1. Inhibitors resemble the natural substrate
    2. Inhibitors bind non-covalently to a site away from the active site
    3. Vmax is decreased
    4. Km is decreased
    1. Vmax is decreased
    2. Inhibitors resemble the natural substrate
    3. Inhibitors bind non-covalently to the active site
    4. Km is decreased

    Author of lecture Uncompetitive Reversible Enzyme Inhibition – Enzyme Inhibitors

     Kevin Ahern, PhD

    Kevin Ahern, PhD

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