[MUSIC] Hello everyone, my name is Seyun Kim, welcome back to my Coursera class, Biochemical Principles of Energy Metabolism. I just finished the introduction of glucose oxidation process. And during this, the second session of Week 3, I'm going to introduce the first phase of glucose degradation which is glycolysis. So glyco means glucose sugar, And lysis means split. So glucose splitting reaction is the first stage of cellular respiration glucose degradation. So, by definition this step is a biochemical reactions that extract a little bit of energy from glucose molecules by splitting it into pyruvate, okay? So this is the glycolysis, the whole reaction. So six carbon containing glucose carbohydrate will be phosphorylated by consuming ATP molecules. This is a little bit interesting, in he very beginning of glycolysis, instead of extracting ATP molecules immediately first we invest our energy. That means we use ATP molecules. Basically glucose molecules will be phosphylated by consuming ADP molecules. That phase is so called energy investment phase. And then we extract ATP four ATP molecules. And during these oxidation processes we can obtain the reduced NADH electron carriers, so final product is pyruvate, as I said this is three carbon containing smaller carbohydrate organic compound. So step number one is glucose phosphorylation. So when the target cells absorb glucose inside the cytosolic compartment of the target cell. So immediately glucose molecule will be, phospholilated. So this reaction is mediated by hexokinase, hexo means six terms C6 like glucose sugars will be phospholilated. So kinase is collectively Indicated as an enzymes that catalyzes the transfer of phosphoryl group of ATP to acceptor substrate. In this case, glucose is substrate for phosphorylation, so as you see ATP molecules define all the gama phosphate will transfer to the glucose molecules, this is step number one in the very, very beginning of glycolysis. The very first chemical reaction of cellular respiration. So what's the main, Function for this phosphorylation? Once glucose is phosphorylated, that phosphorylation event can make the glucose molecules trapped inside the cytoplasm of the target cells, because of this negatively charged phosphate modification. Make this glucose molecules cannot just diffused away from the target cells, because of this charge, this glucose is phosphate cannot just diffuse the ways through your passive diffusion process. So another major function for this phosphorylation means, the phosphate attachment chemically destabilizes and activates the target glucose molecules which can further drive it's downstream degradation processes. So glycolysis is composed of total biochemical reactions. So you're right now in looking at the first five steps. When you see this slide, first, you have to carefully look at the number of carbons, so in the beginning, glucose is 6 carbon. So first, as I said, by using ATP molecules, hexokinase can phosphorylate glucose in the form of glucose-6-phosphate. And then we consume another ATP molecule, and the sugar will be finally phsopholated by two phosphate. This is fructose one-1, 6-biphosphate so right now you're looking at C6 carbohydrate having two phosphate, okay. And this molecule will be degraded into, 3 carbon containing smaller organic compound. So dihydroxyacetone-phosphate, glyceraldehyde-phosphate, and those details are not that critical at this stage, just follow the biochemical concept. The main point of this, the first half of this glycolytic biochemical pathway means, investment of two ATP molecules. To metabolically this glucose and then further to drive the split of this glucose into C3 smaller downstream product. What about the other half reactions in the glycolisis? In this phase, we can abstract energy released from the biochemical degradation pathway, and we can obtain ATP, precious ATP and then product pyravates. And further during these oxidation processes we can generate reduced electron carrier and ADH and reduced electron carriers. Okay, it's time to harvest energy, okay thus C3 compound, intermediate will be oxidized. So oxidizes that means they're losing electrons. That electrons lost from this reaction. Step number six will be captured by using NAD+ electron carrier. And then phosphate group attached. The main point is this C3 compound also doubly phosphorylated. And this highly energetic and the phosphate group potential is really, really high. So ADP substrate can very efficiently obtain the high energy phosphate in the last position of ATP molecules and ATP finally can be generated. And further there is one more step of ATP production, in the last, the step number sixth. And the pyruvate can be generated as a final product of glycolysis. So interesting point is during this. Okay, I'm going back to the previous slide. So we extract ATP molecules. When you see this diagram, the high energy phosphate group transfer potential is utilized to drive the synthesis of ATP molecules at two different steps. So I'm going to explain this phosphorylation event, so called substrate level phosphorylation. What does that mean? This means in the formation of ATP, we use the highly activated metabolic intermediate, which contains high phosphoryl group transfer potential in this case, This is final step of glycolysis. So looking at phosphoenol pyruvate acid this phosphate, the phosphoenol transfer potential is very, very high. Simply speaking, these phosphoenol pyruvate molecule, this metabolic energy status, is very, very unstable and really contains high energy free energy potential. So that phosphate will be transferred to the incoming self substrate ADP, and then ATP can be generated. So in terms of bio energetics, the generation and production of ATP. The first well known classical example, biochemical principle of ATP synthesis is this substrate-level phosphorylation. One of our key metabolic pathways can be used to directly drive the synthesis of ATP by phosphorylating this ATP. And this is product pyruvate. And in the middle in addition to extracting free energy in the form of ATP, we also generate reducing powers. This is so called NAD nicotinamide adenine dinucleotide, this is structure. So NAD is simply speaking electron carriers. So in the middle of the oxidation of glucose molecules and those metabolic intermediates, when they are oxidized so electrons will be captured. Captured and then the acceptor is NAD, oxidized NAD. Oxidized NAD accept electrons in particular this ring structure, and then, the electrons throughout the oxidation processes will be transferred into NAD oxidized form and finally reduced NADH + H+ can be generated. So NADH this is reduced form reduced form. And NAD + this is oxidized form. They can transfer electrons and we can measure the potential because this is electron transferring potential, their three energy changes will be measured in a form of volt, okay? This NADH reduction, NAD+ reduction oxidation process is 0.32V electron transfer potential will be generated. And we can calculate their transfer potential, electron transfer potential in a form of Gibbs free energy, this calculation. You don't need to remember details, but the thing is during the oxygen of glucose molecules when those electrons out of oxidation processes, when they are captured in the form of NADH and this electron transfer potential gives us 61.7 kilo Joule per mole of energy. Which means a lot, and finally this oxidation reduction coupled, free energy will be used to produce a lot of ATP molecules. So glycolysis is the first step for glucose degradation, and cellular respiration. As you see, energetically, this process is not that efficient, rather it's quite a low efficient process, because we obtain only four ATP molecules. Only four ATP molecules by glucose. Of course, in this case, glucose is not fully oxidized, only it's just a matter of splitting of C6 chain in the form of pyruvate. C3 molecular compound, but, overall just quantitation of energy obtained from this process is not that high. And this reaction, there is no point for oxygen consumption. So because of that we call this process anaerobic reaction an means without, so aerobic means oxygen. So this reaction doesn't require any oxygen. So that's why we just believe that this process probably evolved very, very early. Just think about the very primitive earths atmosphere there was a little bit of oxygen, right? At that early period like glycolysis and energy of production, just evolved in the very, very beginning, and then later oxygen-dependent respiration processes are developed. And this glycolysis occurs inside the cytoplasm and does not require any membrane-bound organelle. So, as you can see obviously this glycolysis, the first reaction of cellular restoration is a highly conserved, quite primitive metabolical pathway.
