Glycogen Metabolism: Glycogen Breakdown

00:01 Now the metabolism of glycogen turns out to be relatively simple compared to other metabolic pathways that I have talked about in these presentations.

00:09 The complexity of glycogen actually relates to its regulation.

00:13 We see on the screen a depiction of the way in which glycogen is broken down.

00:18 So glycogen is broken down by an enzyme called glycogen phosphorylase and in many places this is abbreviated and simply called phosphorylase.

00:28 As we will see there are a couple of different forms of phosphorylase for consideration.

00:34 Now glycogen phosphorylase is an interesting enzyme in the way that it breaks glycogen down.

00:39 Many molecules like sugars and so forth are broken down by hydrolysis using water to break bonds.

00:48 Glycogen phosphorylase does not use water. Instead it uses phosphate as you can see here.

00:54 And so this is, instead of being called a hydrolysis, is called a phosphorolysis.

00:58 Now that's not just not an important thing of nomenclature.

01:02 But rather it actually is saving the cell energy, as we shall see.

01:06 The phosphorolysis of glycogen results in production of a molecule called glucose-1-phosphate that you can see on the lower left and a glycogen that's been reduced by one residue.

01:17 So what has happened in this catalytic action, is that the enzyme has broken the bond, the 1,4 bond between the end of the glycogen chain.

01:26 Now it's important to recognize that glycogen phosphorylase works only on ends. It doesn't cut in the middle, it works on ends and it's subsequently chose its way into a glycogen.

01:37 So one of the reasons that the branchedness as it were of the glycogen is important is; because, that the more ends there are, the more glycogen phosphorylases can start on ends and subsequently release a tremendous amount of glucose very quickly.

01:53 We heard stories about somebody who is in a terrifying situation. They do incredible feats of lifting something heavy that which seems otherwise impossible and the ways in this happen actually happens because of the branchedness of glycogen which releases this burst of glucose that people use to accomplish what they do.

02:14 Glucose-1-phosphate is readily turned into glucose-6-phosphate by the enzyme phosphoglucomutase.

02:20 Now this is a reversible reaction, as you can see.

02:23 The significance of the reaction though is that glucose-6-phosphate is produced and if we remember we started with a glycogen that had glucose that had no phosphates on them.

02:34 We have at this point an intermediate in glycolysis, glucose-6-phosphate, that does have a phosphate on there.

02:40 And that phosphate got on there not not by the use of ATP.

02:44 If you recall from the glycolysis presentations hexokinase uses an ATP to put a phosphate onto glucose to make glucose-6-phosphate.

02:54 Here this phosphate got put onto the glucose from the glycogen by using a phosphorylases reaction that did not require ATP.

03:02 This saves the cell energy.

03:04 And the energy for putting that phosphate on actually came from the breaking of the 1,4 bond by the glycogen phosphorylase.

03:11 So cells are very efficient. Cells use whatever they have available to them to do things as efficiently as possible and this is a very good example.

03:21 Now glycogen breakdown proceeds, as I said, by the action of glycogen phosphorylase working from ends and I also noted that glycogen is a very branch molecule.

03:31 We can see on the screen here a branch of glycogen and learn a little bit about the way that glycogen phosphorylase works.

03:38 You see on the top, the branch, and you see the end of the molecule where we have 10 different blue residues that are shown on the left.

03:46 Those 10 residues are all targets for glycogen phosphorylase.

03:51 So as the enzyme acts, it goes through and it releases those 10 subsequently in the reaction that I showed in the beginning of this lecture.

04:00 It takes 10 phosphates and 10 glucose-1-phosphate are produced as a result.

04:05 Now at that point, glycogen phosphorylase won't go any further.

04:09 So glycogen phosphorylase has a limit in how close to a branch it will work.

04:15 You know that the branch is at the base of the yellow molecule, shown on the very top.

04:21 Now as we moved down to the second part, you see we have changed the color of those glucose. So that three of them are still in yellow and 1 is now shown in the sort of orange color and there is a reason for that.

04:32 There is an enzyme called debranching enzyme that plays the second role in breaking down glycogen.

04:38 Debranching enzyme takes the 3 yellow residues that you see in the square and transfers them down to the chain below.

04:46 So because glycogen phosphorylase can only work within about 4 units of a branch this debranching enzyme plays the important role of rearranging molecules so the glycogen phosphorylase will have additional substrates to work on.

05:00 Debranching enzyme is also interesting in another respect that is it actually catalyzes two different reactions.

05:06 The first reaction you can see on the screen which is the transfer of the 3 residues of glucose down to the lower chain.

05:13 What's left behind is that single molecule that is shown above the main chain.

05:19 That's single molecule has that α-1,6 bond that's part of the glycogen branching.

05:28 That last molecule is removed by a hydrolysis reaction. So water is actually used to release that and glycogen debranching enzyme catalyzes that reaction.

05:39 So it's a very flexible, it's a very remarkable enzyme in doing what it does.

05:43 But because of that you can see that an unbranched form is now left behind and glycogen phosphorylase can come back in and continue the phosphorolysis that it was doing originally.

05:56 I should also note one of the point here and that is that the release here of glucose is the only place in glycogen metabolism where free glucose is released.

06:04 All other releases are glucose-1-phosphate.