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Covalent Modification – Metabolism and Regulation

by Kevin Ahern, PhD
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    00:00 enzyme "We're ready to go." Now with respect to covalent modification, I want to give an example about how covalent modification is used to control enzymes and also illustrate another principle. What you see on the screen is a regulatory scheme for controlling the metabolism of glycogen.

    00:16 Now when we think about the metabolism of glycogen, glycogen is a storage form of glucose. One can make glycogen, which means one uses glucose to make glycogen or one can breakdown glycogen, which means one converts glycogen into glucose that the cell can use. These two pathways, catabolic and anabolic, are important to be controlled, because we don't want both of these going on at the same time. Well the scheme that's shown on the screen is the way that cells actually control these two pathways and they control them simultaneously.

    00:47 Now this is important because these two pathways are occurring in the same location in the cell. Now I'm not going to go through the entire pathway here because that's actually the subject of another molecule, but I want to have your focus on protein kinase A that's in the middle. Protein kinase A is a kinase and what kinases do, is they put phosphates onto things. By putting a phosphate onto phosphorylase kinase, phosphorylase kinase becomes activated.

    01:12 And phosphorylase kinase being a kinase, it can put a phosphate onto something else and the something else it puts it on to, is glycogen phosphorylase. That causes glycogen phosphorylase A to become active. In addition to phosphorylase leading the phosphorylase kinase and phosphorylase beta as shown on the right side, protein kinase A can also phosphorylate another important enzyme in glycogen metabolism and this enzyme of course is glycogen synthase. Glycogen synthase can be phosphorylated as shown here and when it phosphorylates this enzyme, it actually inactivates the enzyme, converting it into the B form. The B form of glycogen synthase is the inactive form.

    01:57 Now the principle that I'm illustrating here, is that one enzyme, protein kinase A, is actually doing two things at the same time. It's turning off the enzyme that synthesizes glycogen at the same time as it's activating the enzyme that breaks down glycogen. This phenomenon is known as reciprocal regulation and it's a very important principle in understanding the control of metabolic pathways. With reciprocal regulation, the same action is having opposite effects on catabolic and anabolic processes. The catabolic process here being glycogen breakdown, the anabolic process being glycogen synthesis. Phosphorylation of the respective enzymes is having opposite effects on those two processes.


    About the Lecture

    The lecture Covalent Modification – Metabolism and Regulation by Kevin Ahern, PhD is from the course Biochemistry: Basics.


    Included Quiz Questions

    1. It has opposite effects on catabolic and anabolic pathways
    2. It is the same as feedback inhibition
    3. It always involves ATP, ADP, or AMP
    4. It reverses the direction of all enzymatic reactions in a pathway
    1. Glycogen synthase
    2. Phosphorylase kinase
    3. Glycogen phosphorylase
    4. Glycogen branching enzyme
    5. Mutase

    Author of lecture Covalent Modification – Metabolism and Regulation

     Kevin Ahern, PhD

    Kevin Ahern, PhD


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