Glyoxylate Cycle

00:01 A cycle that’s related to the citric acid cycle is known as the glyoxylate cycle.

00:06 Now, the glyoxylate cycle is only found in bacteria and in plants.

00:11 So it’s not found in animals.

00:13 But, it’s important to understand, to better understand the limitations of some of the metabolism that we find in animals.

00:21 The glyoxylate cycle uses several of the reactions that are found in the citric acid cycle.

00:27 Specifically, the glyoxylate cycle bypasses the decarboxylations of the citric acid cycle.

00:34 And I’ve overlaid the reactions of the glyoxylate cycle here, on the reactions of the citric acid cycle to show you better how the two cycles are related to each other.

00:44 The orange arrows in the center of the figure here, show you the reactions bypassing the reactions of the citric acid cycle and this is made possible by the use of two unique enzymes by the glyoxylate cycle.

00:59 Now, this slide shows a little better overview focused solely on the glyoxylate cycle.

01:05 If we start the process like we started with the citric acid cycle of the glyoxylate cycle, adding an acetyl-CoA, we can form citrate from oxaloacetate.

01:16 Now, that’s shown in the reaction on the center of the screen moving upwards in the direction of citrate.

01:22 The second step of the process is just like the second step of the process of the citric acid cycle.

01:28 Aconitase catalyses the conversion of citrate into isocitrate.

01:33 The next step in the process, however, is where the two pathways differ from each other.

01:38 The enzyme isocitrate lyase, unique to the glyoxylate cycle, catalyses the formation of two molecules.

01:46 One molecule containing four carbons which is succinate, which you have seen before in the citric acid cycle and one new molecule that has two carbons called glyoxylate and this molecule that gives the cycle its name.

01:59 Now, glyoxylate is important in plants and I won’t go into that here.

02:03 But suffice it to say that glyoxylate, can be converted into malate by the addition of an acetyl-CoA.

02:11 This reaction is catalyzed by the enzyme known as malate synthase.

02:15 Now, malate synthase of course is the other enzyme of the glyoxylate cycle that’s unique to it.

02:21 So we can see at this point, that this cycle has used two molecules of acetyl-CoA.

02:28 So keep in tract of everything that we’ve done.

02:30 We made the succinate.

02:32 The succinate can be made into fumarate, by the enzyme fumarase as we have seen before, and fumarate can be made into malate by the enzyme malate dehydrogenase.

02:42 Well, if you’re keeping tract, at this point, we have two molecules of malate, not one.

02:47 So, it’s here, where the glyoxylate cycle is noticeably different than that of the citric acid cycle because in the next step, when malate is converted to oxaloacetate, of course, we have two oxaloacetates.

02:59 In the end of the citric acid cycle, we only had one oxaloacetate.

03:03 That means, that each turn of the glyoxylate cycle is outputting an extra oxaloacetate that can be used for other purposes.

03:12 One of those other purposes that can be used for, is to make glucose in the process of gluconeogenesis.

03:18 Now, the consequences of these, are the plants and bacteria can use acetyl-CoA, as a molecule to make glucose.

03:28 Animals can’t do that, at least not in that amounts.

03:31 And it’s one of the reasons why fat is an important nutrient to store energy because it is not readily converted into glucose.

03:40 Now, the enzyme isocitrate lyase, looking at the reaction that it catalyses, up close, we can see here, the six carbon molecule isocitrate is converted into the four carbon molecule succinate and the glyoxylate shown in this structure on the right.

03:57 The enzyme malate synthase, catalyses the convertion of acetyl-CoA and joins the acetyl group to glyoxylate to form the molecule L-malate.

04:07 As I noted, these two enzymes are unique to the glyoxylate cycle and are not found in animals.

04:13 So in summary, the glyoxylate cycle inputs four carbons in the form of two molecules of acetyl-CoA.

04:20 But in contrasts to the citric acid cycle, it does not release any carbon dioxide molecules.

04:26 And it is because of this, that the glyoxylate cycle is able to produce that extra molecule of oxaloacetate.

04:34 There are only two oxidations that occur in the glyoxylate cycle.

04:38 The formation of FADH2 and the formation of an NADH.

04:42 And these occurs in each turn of the cycle.

04:44 And so, there is the possibility in the glyoxylate cycle because of the production of the extra oxaloacetate to do net synthesis of glucose from acetyl-CoA.

04:54 The citric acid cycle by contrast, input two carbons, in the form of 1 acetyl-CoA.

05:00 It only released two molecules of carbon dioxide, and had four oxidations, and produced three molecules of NADH, one of FADH2, and one of GTP per turn of cycle.

05:12 In terms of the energy, the citric acid cycle is therefore able to produce a lot more energy than the glyoxylate cycle is.

05:19 However, the downside of the citric acid cycle is that there is no net synthesis of glucose possible from acetyl-CoA.