[MUSIC] >> Hello, everyone. Welcome back to my Coursera class, Biochemical Principles of Energy Metabolism. So this is week seven, the final week of this class. So I'm going to introduce six different topics. So in the beginning, it's about metabolic response to starvation condition and the second one is about stress hormone dependent metabolic action. And the third one is about biochemical events taking place in response to exercise. And with four, it's about ethanol metabolism. What is the metabolic consequences after the ethanol alcohol consumption and the session five is about cancer cell specific energy metabolism. And finally, session seven includes the importance of gut microbiota and their actions in the regulation of bioenergetics. Let me begin with the changes of biofuels during starvation in the first session. That's what first session is about starvation dependent metabolic processes. So we're looking at plasma levels on the Y-axis and the days of starvation on the X-axis. So as I explained, glucose is the primary vital nutrient energy source for many peripheral cells and tissues. So like brain and heart muscle cells. So in the very beginning around six millimolar glucose maintain and it is gradually reduced across the, a chronic starvation situation. And when the carbohydrate consumption is significantly reduced across the starvation even though many metabolic systems are trying to back up and trying to maintain blood glucose level at reasonable amount of levels, but it is very demanding. So instead, fats are degraded from adipose tissue and they are released. So fatty acids levels are gradually increased, because fatty acids are readily available a second class nutrients. So they are degraded from adipose stored triacid glycerols and released. And on top of those two glucose and fatty acids, very interestingly, the third class of biofuels are coming up. They are called ketone body. A collection of very unique biochemical metabolites. So ketone bodies are produced and then are released into circulatory system. So the main concept of this first session is about ketone body formation. So what is ketone body? So ketone bodies are very interesting metabolic products and these ketone bodies produced from fatty acid beta-oxidation in the very beginning. But ultimately, they are produced through the ketogenic biochemical enzymatic reactions and this ketogenesis occurs in the liver. So hepatocyte synthesize ketone bodies out of fatty acids. So ketone bodies become very, very important fuel sources in particular for brain and hearts in response to chronic starvation condition. And secondly, again, the liver cells can break down amino acids, protein breakdown so-called proteolysis and those amino acids are utilized to drive gluconeogenesis. So many amino acids can be catabolized into metabolic intermediates essential for gluconeogenesis to produce and then release glucose from the liver cells to the system. And ultimately, peripheral tissues. So ketone bodies and ketogenesis. So there are three types of ketone bodies available, acetoacetate, beta-hydroxybutyrate and acetone. Again, they are produced from the liver by using the fatty acids as substrate under the chronic starvation condition as well as medical situations like the diabetis mellitus. And those ketone bodies are utilized by other tissues, in particular brain and heart and muscle cells. They are very ready to utilize ketone bodies to drive our ATP synthesis. So two molecules of acetyl-CoA. Those acetyl-CoA can be produced from fatty acid of beta oxidation and they are condensed and then more acetyl-CoA required. And finally, the intermediate beta-hydroxy-beta-methylglutaryl-CoA enzyme and they can be split into acetate or acetone and hydroxybutyrate. In particular, acetone, this molecule is not required for a further energy ATP synthesis. Simply it's created in the urine. However, those two, acetoacetate and beta-hydroxybutyrate. Once they are released from liver cells throughout this ketogenic metabolic reaction. And finally, imported into our brain cells and heart cells and they are being utilized to synthesize acetyl-CoA back to acetyl-CoA. And those acetyl-CoA are fully oxidized throughout the chronic acetyl cycle and acetyl-phospho formation. That is the ketogenesis. So in particular in the context of ketogenesis, I want to emphasize the importance of medical condition called the diabetic ketoacidosis. So this is very detrimental situation like life-threatening complication caused from the diabetes. So this situation means like extremely high levels of ketone bodies produced and detected in the diabetic patient. So situations like this. So in the absence of insulin or under the insulin resistance situation. So liver cells cannot efficiently uptake glucose and rather release glucose through the gluconeogenesis. And in particular, so one of key intermediates for gluconeogenesis is oxaloacetate. And oxaloacetate is also very important to drive the TCA cycle in the mitochondria. So the situation's like this. So under the huge or active fatty acid degradation in the liver from the diabetic patient. I mean, the more like the terminal stage of diabetic patient. So acetyl-CoA levels will be increased. But the thing is because of the depletion of oxaloacetates within the liver, acetyl-CoA cannot be used to going to the TCA cycle and rather this acetyl-CoA are used for massive ketogenic programs like ketogenesis. So finally, those of ketone bodies are released into the circulatory system and blood pH rapidly drops. So acidosis become acidic, because the ketone bodies are acids. So because of this, a huge amount of ketone bodies. So finally, patient can undergo coma and more like death if appropriately untreated. So this is one of the important aspects of ketogenesis, regulation of ketogenesis, in particular in the context of diabetes.