Hello, everyone. Welcome back to my Coursera class, Biochemical Principles of Energy Metabolism. This is the third session of week seven. And this is about exercise. So exercise is one of the most effective ways to manage metabolic syndromes, including obesity and diabetes. So this is very clear. You know, exercise is kind of medicine. Its very very important. And in particular, this area, exercise physiology and exercise and related bioenergetics is kind of one of active area of investigation. So let me begin with the lactic acid fermentation. So just think about the chronic, sorry about that not chronic. On a short term, anaerobic strenuous exercise, right. And during those anaerobic exercise, ATP, unstored ATP, and stored creatine phosphate was too high energy containing molecules are regularly used up. Exhausted in 7-10 seconds of continuous strong muscular activity and the metabolic processes, it's like this: So, glucose molecules will be oxidized, integrated through the glycolysis and pyruvate produced, right. So, in a normal situation, normal oxygen, in which situation, those two pyruvates are fully oxidized into CO2 and many many many ATP molecules, right. That is a cellular respiration. But the issue is those anaerobic condition under the strong muscular activities. Those two pyruvates will be regenerated and rather oxidized back into the lactic acid. And the main reason for this process called the lactic acid fermentation, the NADH, those reducing power will be consumed and then NAD+ oxidize form will be regenerated. And without NAD+ concentration, glucose cannot continuously integrate it. So to make sure the glycolytic rate is highly maintained in side of muscular tissue, skeletal muscular tissue, this pyruvate instead of being fully oxidized into CO2 and OHP molecules rather, these pyruvate molecules transformed into lactic acid. All right. And then, when the lactic acid is a typically and highly accumulated inside the skeletal muscles, people can feel muscle fatigue and muscle pain. This is still very fundamental metabolic process in response to muscular exercise activity. And then, bio energetically, what's going to happen to those lactate? And those lactate produced and accumulated inside the muscle will be released, will be inside the muscle. A lactate will be accumulated and they're released into bloodstream and those lactate transported into liver, to keep organ for metabolic reactions in your body. And then these lactates getting back to glucose molecules, and and these glucose molecules will be released and back to the skeletal muscle, right. So what is the main goal of these metabolic cycle so-called Cori Cycle. It's very clear, right. So lactic acid, a product from a muscle fermentation and those lactate will be re-utilized to drive more glucose production to make sure skeletal muscles have enough glucose to sustain high activity, okay. This is concept of Cori Cycle. The inter organ biochemical relationship between muscle and liver to maintain and to sustain enough glucose nutrient levels. So exercise is quite complicated, adaptive physiologic responses in many tissues, in brain and in many peripheral tissues. And overall, a reasonable amount of exercise can increase insulin sensitivity and decrease lower blood pressure and trigger demobilizers of fats and reduce inflammation and stimulate your mood and cognition and even motor functions are will be enhanced, magically. And that is the power of exercise. So biochemically, what's going to happen actually indeed, in this case, in particular skeletal muscle, and again this area of exercise biology or physiology is one of active area of investigation right now. And so I'm going to give you like a fundamental biochemical changes. So exercise, so inside our skeletal muscle tissues intracellular calcium ions will be increased created because the neural triggering stimulate the activation of the release of calcium from the [inaudible] remembering compartment of skeletal muscles into cytosol. So when calcium levels going up, and calcium-dependent protein kinase will be activated. And on the other hand, so during the exercise, ATP will be consumed, right. Muscle contraction consume a lot of ATP. So ADP and AMP levels will be increased. In that case, AMP dependent protein kinase called the AMP kinase will be activated and this one cancel dependent protein kinase activated. And also, very importantly, the intracellular redox molecules like NAD+ will be increased because NADH level will be lowered to drive more ATP synthesis, instead NAD+ will be increased. In that case, very interesting enzyme called the sirtuin, this is NAD+-dependent deacetylase. And those sensors, metabolic signalling factors are activated and overall they regulate metabolic enzymes and the gene expression profiles of target tissues and then drive the metabolic adaptations like fatty acid oxidation or stimulation and then increase of mitochondrial biogenesis. This is very important biochemical aspects of exercise dependent processes and those are indeed very very important for mediating exercise dependent physiologic responses.