1 00:00:00,0 --> 00:00:09,108 Human metabolism encompasses both the catabolic and anabolic mechanisms within 2 00:00:09,108 --> 00:00:17,952 the human body that convert food into energy, tissues, cells, enzymes and other 3 00:00:17,952 --> 00:00:24,139 biological products. If we think of food as chemistry, we can 4 00:00:24,139 --> 00:00:29,347 think of the body like a factory. Some chemicals are used to make the 5 00:00:29,347 --> 00:00:34,19 factory run, others are used to make it more efficient and some create actual 6 00:00:34,19 --> 00:00:39,300 products within the factory. We grow cells, hair, teeth. 7 00:00:39,300 --> 00:00:45,42 We formulate the human organism. From a fetal stage all the way to our old 8 00:00:45,42 --> 00:00:48,276 age. When we look at these food in components, 9 00:00:48,276 --> 00:00:52,786 these chemicals, as you've already learned we can group them into 10 00:00:52,786 --> 00:00:56,410 categories. If we think about energy, the nutrients 11 00:00:56,410 --> 00:00:59,852 we're concerned about are the macro nutrients. 12 00:00:59,852 --> 00:01:06,660 The next set of slides we're going to go over how these gets broken down. 13 00:01:06,660 --> 00:01:09,724 Now, you'll notice here that alcohol does provide calories. 14 00:01:09,724 --> 00:01:15,60 However, for the purposes of this lecture, I won't go in how alcohol is 15 00:01:15,60 --> 00:01:18,967 broken down. We will cover the breakdown of lipids, 16 00:01:18,967 --> 00:01:24,863 carbohydrates, and proteins and you'll get to see why lipids actually have more 17 00:01:24,863 --> 00:01:31,727 calories than the other macronutrients. So let's take a step by step approach and 18 00:01:31,727 --> 00:01:36,486 break down metabolism. So this may seem like a pretty full 19 00:01:36,486 --> 00:01:39,915 figure but we're going to go through it one by one. 20 00:01:39,915 --> 00:01:45,396 The reason, I've put this all together for you is I want you to understand how 21 00:01:45,396 --> 00:01:49,667 all of this works together. We break down all these nutrient 22 00:01:49,667 --> 00:01:54,82 components, fat, carbohydrate and protein to generate energy. 23 00:01:54,82 --> 00:02:02,140 Again, in these series of lectures, we're mainly talking about synthesizing energy. 24 00:02:02,140 --> 00:02:07,402 So let's start with glucose. In the first step of glucose breakdown, 25 00:02:07,402 --> 00:02:13,820 we synthesize for every one glucose molecule, two molecules of Pyruvate. 26 00:02:13,820 --> 00:02:19,277 For this process, we will release hydrogens or electrons. 27 00:02:19,277 --> 00:02:26,350 And NAD, which incidentally comes from niacin, will pick up these electrons. 28 00:02:26,350 --> 00:02:29,960 And deliver them to aelectron transport chain. 29 00:02:29,960 --> 00:02:34,24 That's where all the action happens. That's where the energy's produced. 30 00:02:35,940 --> 00:02:39,148 This process also requires energy, however. 31 00:02:39,148 --> 00:02:46,902 For every two ATPs, four are generated. So in this first step, you actually make 32 00:02:46,902 --> 00:02:52,290 two molecules of ATP. This is a reversible reaction and we call 33 00:02:52,290 --> 00:03:00,874 that Gluconeogenesis. The next step is to break down Pyruvate. 34 00:03:00,874 --> 00:03:08,422 Now, in some circumstances, if oxygen is not available for this process to occur, 35 00:03:08,422 --> 00:03:15,8 Pyruvate is broken down into Lactate. This actually happens in the case of high 36 00:03:15,8 --> 00:03:19,522 intensity exercise. If you engage in, any kind of sport and 37 00:03:19,522 --> 00:03:25,444 have ever experienced pain in your muscles after an intense workout this is 38 00:03:25,444 --> 00:03:29,640 partially to do with lactate or lactic acid build up. 39 00:03:29,640 --> 00:03:32,300 When you're working out in high intensity. 40 00:03:32,300 --> 00:03:36,521 The oxygen can't always efficiently travel throughout your body, provide 41 00:03:36,521 --> 00:03:41,121 oxygen for Pyruvate break down. So again, Lactate's produced. 42 00:03:41,121 --> 00:03:48,117 When we have enough oxygen, Pyruvate is converted, through the activity of TPP 43 00:03:48,117 --> 00:03:55,826 which is derived from Thiamine. Thiamine pyrophosphate, with the addition 44 00:03:55,826 --> 00:04:04,325 of CoA, CoA, regenerate two acetyl-CoA's. So again, the action of TPP, thiamine 45 00:04:04,325 --> 00:04:10,880 pyrophosphate coming from thiamine. The addition of two CoA molecules. 46 00:04:10,880 --> 00:04:16,812 We generate Acetyl CoA. For this process we also generate an 47 00:04:16,812 --> 00:04:21,149 electron. Here again, NAD comes in, picks those 48 00:04:21,149 --> 00:04:25,168 electrons up. Since then, the electron transport chain. 49 00:04:25,168 --> 00:04:31,982 In this conversion, we also produce carbon and we use oxygen. 50 00:04:31,982 --> 00:04:38,13 To convert that free carbon to carbon dioxide, this is what you breath out. 51 00:04:38,13 --> 00:04:42,916 Right, so now we come to Acetyl CoA, we can't go back. 52 00:04:42,916 --> 00:04:46,928 Acetyl CoA does not go back to Pyruvate, and will then will not go back to 53 00:04:46,928 --> 00:04:50,966 glucose. The next step, we're just focusing on 54 00:04:50,966 --> 00:04:55,841 breaking of glucose. Is the combination of acetyl-CoA and 55 00:04:55,841 --> 00:04:59,161 oxaloacetic acid in the citric acid cycle. 56 00:04:59,161 --> 00:05:03,166 These two compounds are joined to create citric acid. 57 00:05:03,166 --> 00:05:08,809 And since this is a basic course, we won't go into very detailed of the 58 00:05:08,809 --> 00:05:14,551 synthesis of citric acid towards oxoacetic acid, or I should say, the 59 00:05:14,551 --> 00:05:18,316 breakdown. But understand overall that this 60 00:05:18,316 --> 00:05:24,718 conversion of citric acid to oxoacetic acid generates more electrons with the 61 00:05:24,718 --> 00:05:29,940 help of NAD as a carrier, going to the electron transport chain. 62 00:05:29,940 --> 00:05:36,552 More carbon dioxide, a unique energy molecule called GTP, guanosine 63 00:05:36,552 --> 00:05:44,618 triphosphate, which is similar to ATP. And some more electrons would help up FAD 64 00:05:44,618 --> 00:05:51,638 which actually comes from riboflavin. Again, taking those electrons to the 65 00:05:51,638 --> 00:05:56,950 electron transport chain. So you can see quite a bit of energy is 66 00:05:56,950 --> 00:06:03,174 generated in the citric acid cycle. Once all these different sources of 67 00:06:03,174 --> 00:06:09,941 electrons reach the electron transport chain, they can be further processed to 68 00:06:09,941 --> 00:06:17,290 generate water and energy. Energy ATP equals calories. 69 00:06:17,290 --> 00:06:22,670 Calories fuel our body. The energy in our food becomes our 70 00:06:22,670 --> 00:06:30,706 energy. So what might happen if we don't have 71 00:06:30,706 --> 00:06:37,159 enough Pyruvate? If we look back into the figure, we that 72 00:06:37,159 --> 00:06:42,205 Pyruvate comes from glucose and if someone were not to consume enough 73 00:06:42,205 --> 00:06:47,158 glucose, say, on a local diet. We have produced synthesis of Pyruvate 74 00:06:47,158 --> 00:06:50,400 and that's reduced availability of Pyruvate. 75 00:06:50,400 --> 00:06:56,416 Well, in addition to synthesizing Acetyl-CoA, breaking carbon down to make 76 00:06:56,416 --> 00:07:01,20 Acetyl-CoA, we also get Oxaloacetic Acid from Pyruvate. 77 00:07:01,20 --> 00:07:07,910 So even if we get more Acetyl-CoA from the other macronutrients from lipids or 78 00:07:07,910 --> 00:07:12,944 from proteins. Reduction in Pyruvate availability will 79 00:07:12,944 --> 00:07:19,124 also reduce the availability of Oxaloacetic Acid and reduce the citric 80 00:07:19,124 --> 00:07:22,140 acid cycle. So what happens if we don't have enough 81 00:07:22,140 --> 00:07:26,40 Pyruvate, how would this happen? Maybe if we're on a low carb diet, or for 82 00:07:26,40 --> 00:07:30,742 another area we don't get enough glucose. Now you can look into more reasons why 83 00:07:30,742 --> 00:07:35,215 Pyruvate synthesis might be impaired, or the breakdown of glucose might be 84 00:07:35,215 --> 00:07:39,80 impaired. We don't have enough Pyruvate. 85 00:07:39,80 --> 00:07:43,296 Certainly we'll make less acetyl-CoA. We breakdown less Pyruvate less 86 00:07:43,296 --> 00:07:48,105 acetyl-CoA, but also we'll have less availability of Oxaloacetic Acid. 87 00:07:48,105 --> 00:07:53,532 Regardless of what's happening with the other macronutrients, we'll learn in a 88 00:07:53,532 --> 00:07:57,277 moment that fat and protein can both make Acetyl-CoA. 89 00:07:57,277 --> 00:08:02,917 If we don't have sufficient Pyruvate, we'll reduce the availability of 90 00:08:02,917 --> 00:08:07,599 oxoacetic acid as well. When we do this, we're going to reduce 91 00:08:07,599 --> 00:08:11,498 the production of citric acid. Of course we're not talking about 92 00:08:11,498 --> 00:08:15,320 stopping the production, but we certainly would reduced the citric acid cycle. 93 00:08:15,320 --> 00:08:21,337 Slow down the cycle. Slow down the generation of energy from 94 00:08:21,337 --> 00:08:24,140 Acetyl-CoA. Where does all this Acetyl-CoA go? 95 00:08:24,140 --> 00:08:27,110 If you're not eating carbohydrates, but you're still eating proteins and fat, 96 00:08:27,110 --> 00:08:31,737 where does it go? On this case, say with a little carb 97 00:08:31,737 --> 00:08:35,700 diet, Acetyl CoA is converted into Ketone bodies. 98 00:08:35,700 --> 00:08:41,95 The synthesis of Ketone Bodies can occur for many reasons and you can take some 99 00:08:41,95 --> 00:08:46,484 time to look this up in greater detail. You can look it up in regards to not not 100 00:08:46,484 --> 00:08:52,648 only a low carb diet. But also in diabetes. 101 00:08:52,648 --> 00:09:02,608 For now we'll go on and talk about the breakdown of some of the other macro 102 00:09:02,608 --> 00:09:10,706 nutrients. So here we are again back to the overall 103 00:09:10,706 --> 00:09:17,925 picture. Let's look at triglycerides. 104 00:09:17,925 --> 00:09:32,545 In triglyceride breakdown, we have fatty acid oxidation, the breakdown of those 105 00:09:32,545 --> 00:09:38,468 fatty acids. Triglycerides are broken down, first by 106 00:09:38,468 --> 00:09:43,16 their glycerol product and their free fatty acids. 107 00:09:43,16 --> 00:09:50,513 This role is actually treated much like our carbohydrates and converted to 108 00:09:50,513 --> 00:09:53,977 Pyruvate. Where it gets interesting is when we're 109 00:09:53,977 --> 00:09:58,171 dealing with a breakdown where the oxidation of our free fatty acids. 110 00:09:58,171 --> 00:10:06,258 What we see here is an energy requiring process. 111 00:10:06,258 --> 00:10:14,448 We have a 2 carbon molecule with the addition of a CoA, generating acetyl-CoA, 112 00:10:14,448 --> 00:10:19,388 right back to that main figure we talked about. 113 00:10:19,388 --> 00:10:26,61 This is lipolysis or fatty acid oxidation, breakdown of our fats. 114 00:10:26,61 --> 00:10:31,506 This also involves the pick up of an electron by NADH. 115 00:10:31,506 --> 00:10:35,620 First using by NAD to NADH as well as FAD. 116 00:10:35,620 --> 00:10:41,452 So niacin and riboflavin are important in this process. 117 00:10:41,452 --> 00:10:51,14 This will continue. More energy breaking down more two carbon 118 00:10:51,14 --> 00:10:58,357 at a time, generating a Acetyl CoA. So think about how many carbons are 119 00:10:58,357 --> 00:11:02,140 available in gluclose versus how many carbons are available here. 120 00:11:02,140 --> 00:11:10,70 Or more carbons are available, meaning we can make way more Acetyl-CoA, well, 121 00:11:10,70 --> 00:11:18,199 enough at least to make 9 kilocalories per gram versus 4 kilocalories per gram. 122 00:11:18,199 --> 00:11:23,611 These are reversible reactions, and the synthesis of lipid from acetyl-CoA is 123 00:11:23,611 --> 00:11:28,867 termed lipogenesis. So again, we bring this breakdown of fats 124 00:11:28,867 --> 00:11:36,319 into this overall picture, and we realize that we can generate far more energy from 125 00:11:36,319 --> 00:11:43,41 the breakdown of triglycerides than we can from the breakdown of glucose. 126 00:11:43,41 --> 00:11:56,62 All the polypeptides are protein. Polypeptides can be considered one of two 127 00:11:56,62 --> 00:12:04,680 groups, either Glucogenic. For ketogenic, so remember we, we've seen 128 00:12:04,680 --> 00:12:08,880 this term ketone already, in the ketone bodies. 129 00:12:08,880 --> 00:12:13,682 Either one will be deaminated, removing the NH2 group. 130 00:12:13,682 --> 00:12:20,765 That will be broken down into alternately urea with the addition of carbon dioxide. 131 00:12:20,765 --> 00:12:26,334 And the carbon skeleton. Here it is when we excrete in our urine. 132 00:12:26,334 --> 00:12:33,194 The carbon skeleton that remains from the glucogenic or ketongenic amino acids has 133 00:12:33,194 --> 00:12:37,945 one or two phase. Glucogenic amino acids are converted to 134 00:12:37,945 --> 00:12:41,547 Pyruvate. Hence, the nameglucogenic because you can 135 00:12:41,547 --> 00:12:46,510 go from Pyruvate. To glucose in Gluconeogenesis. 136 00:12:46,510 --> 00:12:51,760 The Ketogenic Amino Acids are converted to Acetyl-CoA. 137 00:12:51,760 --> 00:12:56,359 In the absence of carbohydrate, these would go to ketone bodies, and that's 138 00:12:56,359 --> 00:12:59,635 where we generate this term ketogenic amino acids. 139 00:12:59,635 --> 00:13:04,990 But if we have a plenty of the other nutrients around, acetyl-CoA will enter 140 00:13:04,990 --> 00:13:09,842 the citric acid cycle as before and be broken down to produce energy. 141 00:13:09,842 --> 00:13:15,856 This is again reversible reaction, so we can take carbon skeletons and the 142 00:13:15,856 --> 00:13:23,370 nitrogen to generate new amino acids. So that's where this fits into the 143 00:13:23,370 --> 00:13:27,38 picture again. So we've broken this down step by step, 144 00:13:27,38 --> 00:13:32,982 looked at this relatively complex figure, but seen how it all fits together. 145 00:13:32,982 --> 00:13:38,380 So take a few minutes to review this again. 146 00:13:38,380 --> 00:13:44,210 You can review the slide one more time. And the read the hard time goes wicked. 147 00:13:44,210 --> 00:13:49,948 Print this off to reference to study and learn more about metabolism. 148 00:13:49,948 --> 00:13:56,348 And it maybe something you want to keep as you continue on to your education, as 149 00:13:56,348 --> 00:14:00,842 you learn details of the Gastric Cycle, for example.