Human metabolism encompasses both the catabolic and anabolic mechanisms within the human body that convert food into energy, tissues, cells, enzymes and other biological products. If we think of food as chemistry, we can think of the body like a factory. Some chemicals are used to make the factory run, others are used to make it more efficient and some create actual products within the factory. We grow cells, hair, teeth. We formulate the human organism. From a fetal stage all the way to our old age. When we look at these food in components, these chemicals, as you've already learned we can group them into categories. If we think about energy, the nutrients we're concerned about are the macro nutrients. The next set of slides we're going to go over how these gets broken down. Now, you'll notice here that alcohol does provide calories. However, for the purposes of this lecture, I won't go in how alcohol is broken down. We will cover the breakdown of lipids, carbohydrates, and proteins and you'll get to see why lipids actually have more calories than the other macronutrients. So let's take a step by step approach and break down metabolism. So this may seem like a pretty full figure but we're going to go through it one by one. The reason, I've put this all together for you is I want you to understand how all of this works together. We break down all these nutrient components, fat, carbohydrate and protein to generate energy. Again, in these series of lectures, we're mainly talking about synthesizing energy. So let's start with glucose. In the first step of glucose breakdown, we synthesize for every one glucose molecule, two molecules of Pyruvate. For this process, we will release hydrogens or electrons. And NAD, which incidentally comes from niacin, will pick up these electrons. And deliver them to aelectron transport chain. That's where all the action happens. That's where the energy's produced. This process also requires energy, however. For every two ATPs, four are generated. So in this first step, you actually make two molecules of ATP. This is a reversible reaction and we call that Gluconeogenesis. The next step is to break down Pyruvate. Now, in some circumstances, if oxygen is not available for this process to occur, Pyruvate is broken down into Lactate. This actually happens in the case of high intensity exercise. If you engage in, any kind of sport and have ever experienced pain in your muscles after an intense workout this is partially to do with lactate or lactic acid build up. When you're working out in high intensity. The oxygen can't always efficiently travel throughout your body, provide oxygen for Pyruvate break down. So again, Lactate's produced. When we have enough oxygen, Pyruvate is converted, through the activity of TPP which is derived from Thiamine. Thiamine pyrophosphate, with the addition of CoA, CoA, regenerate two acetyl-CoA's. So again, the action of TPP, thiamine pyrophosphate coming from thiamine. The addition of two CoA molecules. We generate Acetyl CoA. For this process we also generate an electron. Here again, NAD comes in, picks those electrons up. Since then, the electron transport chain. In this conversion, we also produce carbon and we use oxygen. To convert that free carbon to carbon dioxide, this is what you breath out. Right, so now we come to Acetyl CoA, we can't go back. Acetyl CoA does not go back to Pyruvate, and will then will not go back to glucose. The next step, we're just focusing on breaking of glucose. Is the combination of acetyl-CoA and oxaloacetic acid in the citric acid cycle. These two compounds are joined to create citric acid. And since this is a basic course, we won't go into very detailed of the synthesis of citric acid towards oxoacetic acid, or I should say, the breakdown. But understand overall that this conversion of citric acid to oxoacetic acid generates more electrons with the help of NAD as a carrier, going to the electron transport chain. More carbon dioxide, a unique energy molecule called GTP, guanosine triphosphate, which is similar to ATP. And some more electrons would help up FAD which actually comes from riboflavin. Again, taking those electrons to the electron transport chain. So you can see quite a bit of energy is generated in the citric acid cycle. Once all these different sources of electrons reach the electron transport chain, they can be further processed to generate water and energy. Energy ATP equals calories. Calories fuel our body. The energy in our food becomes our energy. So what might happen if we don't have enough Pyruvate? If we look back into the figure, we that Pyruvate comes from glucose and if someone were not to consume enough glucose, say, on a local diet. We have produced synthesis of Pyruvate and that's reduced availability of Pyruvate. Well, in addition to synthesizing Acetyl-CoA, breaking carbon down to make Acetyl-CoA, we also get Oxaloacetic Acid from Pyruvate. So even if we get more Acetyl-CoA from the other macronutrients from lipids or from proteins. Reduction in Pyruvate availability will also reduce the availability of Oxaloacetic Acid and reduce the citric acid cycle. So what happens if we don't have enough Pyruvate, how would this happen? Maybe if we're on a low carb diet, or for another area we don't get enough glucose. Now you can look into more reasons why Pyruvate synthesis might be impaired, or the breakdown of glucose might be impaired. We don't have enough Pyruvate. Certainly we'll make less acetyl-CoA. We breakdown less Pyruvate less acetyl-CoA, but also we'll have less availability of Oxaloacetic Acid. Regardless of what's happening with the other macronutrients, we'll learn in a moment that fat and protein can both make Acetyl-CoA. If we don't have sufficient Pyruvate, we'll reduce the availability of oxoacetic acid as well. When we do this, we're going to reduce the production of citric acid. Of course we're not talking about stopping the production, but we certainly would reduced the citric acid cycle. Slow down the cycle. Slow down the generation of energy from Acetyl-CoA. Where does all this Acetyl-CoA go? If you're not eating carbohydrates, but you're still eating proteins and fat, where does it go? On this case, say with a little carb diet, Acetyl CoA is converted into Ketone bodies. The synthesis of Ketone Bodies can occur for many reasons and you can take some time to look this up in greater detail. You can look it up in regards to not not only a low carb diet. But also in diabetes. For now we'll go on and talk about the breakdown of some of the other macro nutrients. So here we are again back to the overall picture. Let's look at triglycerides. In triglyceride breakdown, we have fatty acid oxidation, the breakdown of those fatty acids. Triglycerides are broken down, first by their glycerol product and their free fatty acids. This role is actually treated much like our carbohydrates and converted to Pyruvate. Where it gets interesting is when we're dealing with a breakdown where the oxidation of our free fatty acids. What we see here is an energy requiring process. We have a 2 carbon molecule with the addition of a CoA, generating acetyl-CoA, right back to that main figure we talked about. This is lipolysis or fatty acid oxidation, breakdown of our fats. This also involves the pick up of an electron by NADH. First using by NAD to NADH as well as FAD. So niacin and riboflavin are important in this process. This will continue. More energy breaking down more two carbon at a time, generating a Acetyl CoA. So think about how many carbons are available in gluclose versus how many carbons are available here. Or more carbons are available, meaning we can make way more Acetyl-CoA, well, enough at least to make 9 kilocalories per gram versus 4 kilocalories per gram. These are reversible reactions, and the synthesis of lipid from acetyl-CoA is termed lipogenesis. So again, we bring this breakdown of fats into this overall picture, and we realize that we can generate far more energy from the breakdown of triglycerides than we can from the breakdown of glucose. All the polypeptides are protein. Polypeptides can be considered one of two groups, either Glucogenic. For ketogenic, so remember we, we've seen this term ketone already, in the ketone bodies. Either one will be deaminated, removing the NH2 group. That will be broken down into alternately urea with the addition of carbon dioxide. And the carbon skeleton. Here it is when we excrete in our urine. The carbon skeleton that remains from the glucogenic or ketongenic amino acids has one or two phase. Glucogenic amino acids are converted to Pyruvate. Hence, the nameglucogenic because you can go from Pyruvate. To glucose in Gluconeogenesis. The Ketogenic Amino Acids are converted to Acetyl-CoA. In the absence of carbohydrate, these would go to ketone bodies, and that's where we generate this term ketogenic amino acids. But if we have a plenty of the other nutrients around, acetyl-CoA will enter the citric acid cycle as before and be broken down to produce energy. This is again reversible reaction, so we can take carbon skeletons and the nitrogen to generate new amino acids. So that's where this fits into the picture again. So we've broken this down step by step, looked at this relatively complex figure, but seen how it all fits together. So take a few minutes to review this again. You can review the slide one more time. And the read the hard time goes wicked. Print this off to reference to study and learn more about metabolism. And it maybe something you want to keep as you continue on to your education, as you learn details of the Gastric Cycle, for example.