Hello everyone. Welcome back to my Cousera class Biochemical Principles of Energy Metabolism. This is week six. So we are looking at the current, the campus, the Cherry Blossom. So I have been recording this course in the middle of April. Please enjoy the beautiful flowers in KAIST campus. This week we are going to study two major hormones in the regulation of bioenergetics and then I'm going to focus on diabetes. The major metabolic disturbance in the context of this regulated energy metabolism. So let's talk about integrative aspects of bioenergetics in the context of fuel sources. Well, I just chose five different organs and tissues like the brain, and cardiac muscle, and liver, and skeletal muscle, and adipose tissue. So interestingly, our organs and tissues have preferences in terms of choosing fields to generate energy. Let's say, in the case of neurons and cells in the central nervous system like brain tissues prefer glucose to other energy sources, like nutrients. So what about the cardium muscles? The cells in the heart, they utilize fatty acid. They prefer fatty acid bad oxidation to other pathways in terms of generating ATP. And the liver, cells like hepatocyte and glucose, fatty acid or even amino acid can be outgraded without any problems. The skeletal muscles, glucose and fatty acids bad oxidation and those two nutrients like, carbohydrates and fatty acids are fuel sources in generating mechanical forces in skeletal myocytes muscle cells. Adipose tissues, obviously, fatty acid based organ. Very interestingly, some organs like brain and heart, there is no fuel reserve available. So that means brain cells and the cardial myocytes, they require constant supply of energy fuels for generating ATP molecules. But other organs like liver, the glucose can be stored in the form of glycogen, the glucose polymer and triacylgylcerol to fat molecule can be stored. And skeletal muscle is more like glycogen-based and the muscular proteins can be used in case of deficient energy conditions. And obviously, triacylgylcerol fuel molecules are stored in adipose tissue. So when you think about the brain and the heart. Right? So regulation of internal organs, and cognition, and psychiatry are controlled by brain systems and heart muscle is obviously, the essential for sustaining life. Right? The circulation of blood and lymphatic fluid. In those systems there's no fuel reserves and, obviously, glucose is the primary source for energy production. So in that sense, blood glucose regulation is very very critical to maintain the basal and the adequate levels of energy production. So the point is, for individual health in humans, the normal blood sugar levels, blood glucose are supposed to be maintained and regulated. So top values over here, under fasting condition this amount of how blood sugar should be maintained, and two hours after eating and still the blood glucose level supposed to be maintained throughout very complicated homeostatic coordination. So, in that sense, when the blood sugar levels, glucose levels, when the level rapidly drops, so the effected human individual in vertebrate organisms may suffer from a lot of symptoms and critical complications. So, which organ is the most critical one for regulating blood glucose homeostasis? Is, obviously, pancreas. So, in particular, the unique anatomical structure, islets of Langerhans inside the pancreas is mainly composed of alpha cells and beta cells and some other accessory cells. And those cells secrete two major hormones like insulin and glucagon. And those hormones are critical for maintaining stable glucose homeostasis. So, let's talk about glucagon for this first session of week six. So you're looking at the islets of Langerhans producing and secreting glucagon called alpha cells. So alpha cells secrete glucagon. And glucagon is very short, 29 amino acid long peptide. And this glucagon is released under what condition? In response to low blood glucose levels. And then when the body requests like more more energy, like under the stressful conditions, or do strenuous exercise situation, and then glucagon is released. So main function of glucagon is like this, elevates the concentration of blood glucose through the gluconeogenesis and glycogenolysis and lypolysis. So gluconeogenesis means the production of glucose. Glucose, neo-newly, genesis-create. So neoglucose can be produced. That biochemical process is gluconeogenesis. The other one is glycogenolysis. Lysis means split. To back up the glucose level in the blood, so glycogen, the glucose polymer, can be degraded into glucose hormonal secrete. The other one is like lypolysis. This is fat. Lypo means lipid, fat-lysis degradation. So fat molecules degraded. Okay. Those catabolic reactions, well, in terms of glycogen degradation, catabolic reactions and gluconeogenesis, glucose production can be stimulated by glucagon hormone. Let's talk about glycogenolysis in the very beginning. As I said, glycogen glucose polymer can be split into glucose phosphate and one glucose reduced shortened glycogen polymer. So this degradation of glycogen to produce, to supply the blood glucose, that reaction takes place in hepatocyte of liver or myocyte in the skeletal muscle. And you are looking at the mode of glycogen action on your left. So, glucagon and or other stress hormone epinephrine and those hormones bind to receptor, and finally activate the degradation of glycogen. And the degraded product, glucose, can be released out of cells, and then get into the circulatory system to maintain the given amount of minimal basal glucose level. So glucagon binds to receptor. Glucagon is the hormone. So glucagon produced from alpha cells of pancreas, and glucagon binds to glucagon receptor, and the very interesting enzyme, adenylate cyclase, or adenylyl cyclase, activated, and this enzyme is very unique. Once it's activated, it can convert ATP into cyclic AMP, the semen's cyclic. And then this cycle again, the molecules, levels going up, and it activate cyclic ATP protein kinase, P protein kinase A. And then throughout interesting phosphorylation cascade, finally, phosphorylase can be fully activated. And this phosphorylase can detach the terminal glucose, the phosphoryleric form of glucose from the glycogen polymer, and that glucose can release their way into the bloodstream. So again, in this glycogen dependent hormone action, the activation of adenylyl cyclase is the key. So this is ATP, our energy molecules. So even though the primary function for ATP is to obviously, to supply the chemical free energy for many, many, many biochemical reactions, in this case, ATP can be used for substrate to generate cyclic AMP. And this cyclic AMP, as you can see, there is a cyclic chemical can be found, and this cyclic AMP is so-called signalling messenger molecules inside the cells. And this cyclic AMP further trigger protein phosphorylation cascade throughout the activated protein kinase A. So, the intracellular increase of this second messenger molecule cyclic AMP control the whole and different types of downstream biological event. The first case is the glycogenolysis, the other one is gluconeogenesis. Cyclic AMP stimulate gluconeogenesis. So, by definition, this is the biochemical reaction essential for degeneration of glucose. So obviously, this is the one of the key biochemical mechanisms of how our body blood glucose levels can be maintained. To avoid the low levels of blood glucose sugar, that phenomenon is called the hypo, hypo means below, hypo glucose level, hypoglycemia. Glycemia is glyce, this is like glucose, the sugar. To avoid those unwanted situation, the gluconeogenesis can be activated in mainly in the liver and some fractions of gluconeogenesis can take place in the kidney. So you are looking at gluconeogenesis biochemical pathway on your left, and glucose, phosphorylation degradation into pyruvate acetyl-coa optysis glycolysis. Those blue lines, glycolysis. Degradation of glucose. So gluconeogenesis pathway is the reversal of this glucose breakdown. This glucose breakdown pathway can be reversed throughout glycogenesis. And then, the substrate to drive this gluconeogenesis, the ultimate source, can be amino acid, or glycerol backbone from the lipid degradation or lactate. So, those substrate in gluconeogenesis can be supplied from the lipid, or amino acid, or even the glycolysis reaction can be simply be first. This is the how hepatocyte in the liver, or kidney cells can generate glucose molecules, and those glucose molecules can be released into the bloodstream. So in this session, we talked about the main actions of glucagon under the low blood glucose levels. So pancreas, alpha cells, secrete glucagon, and those glucagons throughout bloodstreams can be distributed in particular liver or muscle cells in this diagram. The liver activate the glycogen breakdown as well as gluconeogenesis, and that biochemical pathway can be mediated by the synthesis of cyclic AMP as a second messenger. And this is like a liver dependent of summary or maybe and definitely, muscle can be also affected by glycogen or even adipose tissue, adipose tissue can be affected. So as you can imagine, adipose tissues, the lipolysis fat molecules degradation, that pathway can be triggered by glucagon signaling pathway. This is how the blood glucose levels under the fasting condition can be maintained throughout this one of major hormones from the pancreas, I mean, glucagon. So we are going to talk about more throughout those insulin dependent signal activation in the following sessions.
