Reciprocal Regulation

by Kevin Ahern, PhD

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    00:00 Cells use a control mechanism called reciprocal regulation to make sure that futile pathways don't happen.

    00:08 And in reciprocal regulation what the cell does, is it uses small molecules or alterations to one pathway that have opposite effects on the other pathway. So in the case of glycolysis and gluconeogenesis we will see what happens with this.

    00:23 We can see for example here glycolysis shown in blue, going down and gluconeogenesis in yellow, going up.

    00:30 We see that the control points on these pathways are labelled with the PKF and the pyruvate kinase on the right side. The pyruvate carboxylase, the PEPCK and the F1,6BPase on the right side.

    00:41 We notice that they are opposite each other and these enzymes that are opposite each other are regulated by opposite things. So here is how it works.

    00:51 If we look at the activators and an inhibitors of these enzymes, they are as follows.

    00:56 In the case of PFK which controls that essential reaction of going from fructose-6-phosphate to F1,6BP, we see that F2,6BP, the molecule fructose-2,6-bisphosphate, activates PFK and the same molecule inhibits the F1,6BPase.

    01:17 This is a perfect example of reciprocal regulation.

    01:19 We see similar things happening with citrate which is inactivating PFK but it's activating F1,6BPase.

    01:28 Again, AMP has opposite effects, as you can see.

    01:30 Now not everything parallels in the reciprocal regulation.

    01:34 But when we look at what's happening this simple organization that happens with the molecules that you see here allows the cell to use a mechanism to control different pathways with 1 molecule.

    01:48 At the bottom we see that pyruvate kinase is regulated by for example ATP and ATP is an indicator of high energy.

    01:58 So ATP turns off pyruvate kinase which also helps to stop the pathway.

    02:04 We saw ATP for example inhibited the PFK.

    02:08 On the gluconeogenesis side we don't see ATP but we do see ADP, and ADP is an indicator of low energy.

    02:15 Now this makes very good sense; because, the cell doesn't wanna be trying to synthesize glucose under conditions of low energy and the reason for that is, it doesn't have the energy it takes to make the glucose.

    02:27 So this balance in terms of energy or the balance in terms of molecules allows reciprocal regulation to operate and control both pathways in a simple mechanism.

    About the Lecture

    The lecture Reciprocal Regulation by Kevin Ahern, PhD is from the course Metabolic Control.

    Included Quiz Questions

    1. It has opposite effects on catabolic and anabolic pathways
    2. It is a way to reverse processes in cells
    3. It is prevented with ATP
    4. It is controlled by regulating gene expression

    Author of lecture Reciprocal Regulation

     Kevin Ahern, PhD

    Kevin Ahern, PhD

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