Let's cover the reactions specific to gluconeogenesis in the order that they appear in the gluconeogenic pathway; that means that the first reactions we're going to talk about are actually undoing the reaction from the very end of glycolysis. So, these first two reactions we're going to talk about are reversing the action of pyruvate kinase, or reaction number 10 of glycolysis. The reason that this actually has to be done in 2 steps rather than just 1 is that the action of pyruvate kinase is so favorable, right? It cannot be simply undone in just one step. Pyruvate kinase takes PEP, turns it into pyruvate, generates an ATP in the process. These two steps that undo the action of pyruvate kinase and convert pyruvate back into PEP both require energy input in the form of a nucleoside triphosphate. Pyruvate kinase generates an ATP. These two reactions are going to burn 2 nucleotide triphosphates to get back to having PEP. So, the first reaction is carried out by pyruvate carboxylase. This is our first enzyme of the gluconeogenic pathway, and it's going to take pyruvate, turn it into oxaloacetate, and it's going to use an ATP to do that. So, we're going to be left with an ADP. This reaction adds a CO2 to pyruvate. Here we have our pyruvate, and we're actually going to add CO2 onto our pyruvate. The next reaction is carried out by PEP carboxykinase, and this enzyme is going to take that oxaloacetate and it's going to turn it into PEP, and it's going to use a GTP in the process. I always use the phrase "burn" because I like to think of it as using up the energy from the molecule. But I really just mean, you know, break that phosphate bond to harness the energy released. This reaction actually removes the CO2 that was just put on in the previous reaction. So we add the CO2 and then we get rid of it. But in the process, we add on a phosphate group to our oxaloacetate, and that leaves us with PEP. So we are now back at, well, sort of the end of reaction 9 of glycolysis. But, this is actually going to be the beginning of reaction 3 of gluconeogenesis. Moving on to what is reaction 3 of glycolysis, which is carried out by phosphofructokinase or PFK1, as I'm abbreviating it here. Phosphofructokinase is going to take fructose 6 phosphate and add another phosphate group onto it. It's going to be phosphorylated. The enzyme that reverses the action of PFK 1 is fructose 1,6-bisphosphatase. Phosphofructokinase uses a phosphatase to remove a phosphate group. So we're going to take fructose 1,6-bisphosphate, remove a phosphate group, and we are left with fructose 6-phosphate. And of course, this is undoing step 3 from glycolysis. Lastly, undoing the very first reaction of glycolysis, that task is left up to the enzyme Glucose 6 Phosphatase. Remember, hexokinase, that's the first enzyme of the glycolytic pathway, and it's going to act on glucose as soon as it enters the cell and phosphorylate it. Again, we're undoing the action of a kinase with a phosphatase here and going to remove that phosphate group from glucose 6-phosphate and turn it back into glucose. It's worth noting that this enzyme, glucose-6-phosphatase, is actually only present in liver cells. And that's very important because gluconeogenesis is one of the big functions of the liver. And, you know, if you get more into anatomy and physiology, you'll see that the liver plays a huge role in maintaining blood sugar levels. So it makes sense that gluconeogenesis is one of the main jobs of liver cells and it should also make sense that the enzyme needed to complete this process and turn our glucose 6-phosphate into actual glucose, ready to hit the bloodstream and be delivered to the cells, the tissues that need more glucose, that that enzyme would only be present in the liver where this process is being carried out.

Alright. So, just to recap, we are reversing reactions 10, 3, and 1 of glycolysis with the 4 enzymes presented on this page. And reaction 10 of glycolysis takes 2 enzymes to actually undo that step.

Alright. Let's flip the page.