 Welcome back to the lecture series on NPTEL on Animal Physiologies, we are in section 13. So, we are done with the part 1 of section 13 on Metabolism and Temperature Regulation. So, now we are moving on to the part 2. In the part 1, we talked about how the overall flow chart or the overall scheme of things like an anabolism, catabolism, synthesis breakage of another classification of lipids, carbohydrates and proteins. We talked about the absorption of minerals and we talked about how the different individual components of this are through facilitated diffusion and diffusion, co-transport are being absorbed by the intestinal mucosa and being transported at different parts. Then we talked about the Krebs cycle, we talked about the cellular metabolism, we talked about the tricarboxylic acid cycle or Krebs cycle. How from a single glucose molecule through the whole process of cellular metabolism, we produced 36 molecules of ATP. So, today what we will do, we will resume from there. So, we will talk about the other root called gluconeogenesis. So, initially we talked about glycolysis, glyco means carbohydrate, lysis lysis means breaking of carbohydrate. So, when you are breaking a single molecule of carbohydrate, essentially you are obtaining 36 molecules of ATP. Nothing of a situation if you have to follow a reverse rule, when you have to synthesize it. So, when I talked about gluconeogenesis, so you have to just break it down into three parts. Glucone means relevant to carbohydrate, nu means new, genesis means formation, gluconeogenesis. So, we will finish with gluconeogenesis and the flow chart of how gluconeogenesis is taking place. And then we will move on to the lipid metabolism, synthesis of lipid and degradation of lipids and absorption of lipids. And then we will move on to the proteins, the synthesis of amino acid, degradation of amino acids and absorption of amino acids. And then of course, our tail piece will be the temperature regulation. So, let us resume with the gluconeogenesis. So, let us come back to the gluconeogenesis, gluconeogenesis. So, this is what is essentially gluconeogenesis. So, let us get back to the cycle, what is exactly happening. So, we have the glycogen, which are big carbohydrate molecules. This glycogen is through glycolysis is broken down into glucose, from glucose representing glucose by G. Then you have glucose 6-phosphate, then you have, sorry, this is fructose 6-phosphate, then you have fructose 1, 6-bisphosphate, then you have 3-carbon intermediate, from there you have phosphoenol pyruvate PEP, then you have pyruvate acid. And then this enters through acetyl coenzyme A inside the mitochondria. So, let us coming back to the gluconeogenesis part. So, what I will do is that, I will initially talk about again, reiterate all the different steps of glycolysis. And then I will go in the reverse direction, where from the single molecule, single precursor, how the glucose molecules are being formed. So, start with the glycolysis chart, what we have done in the previous class. So, you have the glycogen, glycogen forming your glucose. So, let us come back to the chart, glycogen forming glucose, glucose from glucose to glucose 6-phosphate and to fructose 6-phosphate. And during this process, what is happening? Glucose to glucose 6-phosphate, here basically ATP is being used up. So, that is the phosphate, which is providing sufficient energy. And then from fructose 6-phosphate to fructose 1-6-bis phosphate, again an ATP is being used up to form ADP. And then from 3-carbon intermediate to phosphoenol pyruvate, this is the zone, where both things could happen. ADP, ADP both direction it can run. And from phosphoenol pyruvate to pyruvate acid, this is another region, where from ADP to ATP is formed and out here CO2 is being given out. And from pyruvate acid, your option, there is another option, it can form lactic acid. So, this is how pretty much the whole glycolysis runs. So, when we talked about the gluconeogenesis, we are essentially talking about a reverse mechanism, it will move like this, gluconeogenesis. So, what is essentially happening is that, amino acids are also involved, which could be transformed into carbohydrates. From here, it forms oxaloacetate. In that process, ATP is being used up forming ADP. Oxaloacetate forming phosphoenol pyruvate and in that process, GTP is being used up GDP. From phosphoenol pyruvate, it follows fairly a reverse route it can follow. So, here basically the reverse reaction will be NADH to NAD. And through several steps, it forms a 3-carbon intermediate, then it has options like forming glycerol and from glycerol, whereas fructose 6-phosphate, 1-6-bisphosphate can form other carbohydrates. And these are all the reversible reactions which are taking place. And from here, the other carbohydrate, this could form fructose 6-phosphate. And this whole process, where basically what is happening essentially is that. So, here fructose from fructose, 1-6-bisphosphate gets in water molecule and it gives out a phosphate. And similarly, again it gets hydrolyzed, it takes in water molecule, gives out in phosphate. And in the final term, when from glucose to forming your glycogen, you are using uredine triphosphate to UDP plus phosphate. And this is basically a three enzymatic process and this whole thing is taking place in the cytoplasm. So, basically what I wish to highlight is catabolism and anabolism with little modification follows. They are fairly close by, but some of these cycles are kept fairly conserved, but they do not exactly follow the same route by which they have degraded. There is always kind of bypass and all those things in that whole process. So, those of you are interested really to get in depth into this. They may refer to Lubber destroyer's Birken biochemistry, the ninjas Birken biochemistry, white white biochemistry or Kahn and Stumpf. There you will get much in depth study about glycolysis, gluconeogenesis and the different enzymes, but being a physiology class, I will just give an overall outline of this part of metabolism, which is purely I mean classes and class, I mean like sections of biochemical pathways or metabolism. So, from here I will move on to the lipids. We have talked about the glucose metabolism. Now, let us move on to the lipids, lipid metabolism. So, lipid metabolism again, the site of lipid metabolism is the mitochondria. So, mitochondria as it is being very correctly says in cellular metabolism, this is the powerhouse. This is where most of the reactions are taking place because the TCSI and all these things are taking place in the mitochondria because of and it has one of the most unique feature of electron transport chain, which is functioning and the energy harvesting taking place through chemo-osmotic hypothesis by Peter Mitchell. So, in the mitochondria now we will be talking about lipid catabolism, which follows a beta oxidation pathway. Let us talk about that. So, talk about the lipids now. So, basically beta oxidation is the fatty acid molecules are broken down into two carbon fragment in a sequence of reactions. So, basically what is happening is that fatty acid into two carbon molecule and this whole process of oxidation is called beta oxidation and this process occurs inside the mitochondria. So, the carbon chain can enter the TCSI cycle immediately from here whatsoever this carbon is happening. So, this is all happening inside the mitochondria. So, without much problem this two carbon molecule which is a byproduct of it can move into the get incorporated into the TCSI. So, fatty acids say for example, 18 carbon fatty acids then this consumes ATP and forming AMP adenosine monophosphate plus two phosphate moieties and added up with coenzyme A and it form fatty acid coenzyme A and fatty acid coenzyme A because NAD, NADH in that process produce three ATP in the electron transport chain and then in the second step there is this FAD forming FADH2 and in that process forming another two ATP molecule and again there is another coenzyme A which comes into play. So, essentially what you are having is that fatty acid coenzyme A this fatty acid is C16. So, you start with C18 you will end up with C16 plus acetyl coenzyme A and this acetyl coenzyme A which is formed here becomes part of the TCSI cycle producing 12 ATP molecules. So, you see from 18 carbon chain it becomes a 16 carbon chain in the process with 16 carbon chain it formed an acetyl coenzyme A that gets incorporated into the tricarbosyl acetyl. So, this is how most of the FADs kind of you know breaks down from two molecule. So, 16, 14, 12, 10 likewise their sizes gets chopped off slowly, slowly, slowly, slowly and you will end up with a smaller molecule. So, this is the catabolic process what lipids follows coming back to the slides. So, this is where basically lipid metabolism is happening. So, what about the lipid synthesis? So, we have talked about the catabolism now we will talk about the lipid synthesis. Lipid synthesis is essentially is happening in several ways. So, let us start with the glucose there is a good starting point glucose through glycolysis making pyruvic acid this pyruvic acid forming into acetyl coenzyme A acetyl coenzyme A this pyruvic acid with along with other amino acids and now this is all happening inside the mitochondria and this is all outside is all cytoplasm. So, acetyl coenzyme A I think the steroids amino acids these are all different ways by which all these different molecules are getting incorporated into the cycle. This acetyl coenzyme A which is formed here the one. So, we have this glycerol this glycerol comes here and this acetyl coenzyme A then utilizing NADH forming NAD and in that process here ATP is being consumed to make ADP and secretes coenzyme A leads to the formation of fatty acid. Fatty acid when it makes with the glycerol from glyceride and these fatty acids are involved in formation of several intermediate which includes glycolipid phospholipid I am just putting P phospholipid prostaglandin cholesterol in the membrane if you remember all these things were being present and this whole process is called lipogenesis. So, this is the whole process overall geometry of the lipogenesis and from here what we will do we will talk about the lipid transport and distribution. So, if you look around if you see this cycle as long as your concept about the TCA cycle is clear and you can correlate the different molecules how they are fitting in in the form after forming coenzyme A rest is all kind of you know you can develop from there but you have to at least understand one cycle from where glucose to pyruvic acid and then getting into through acetyl coenzyme A getting into the tricarboxylic acid cycle that concept has to be clarified first once that is clear clear then the rest will fit in there amino acids can fit in there your lipids can fit in there everything can fit in, but you have to first of all understand one basic pathway. So, from here we will talk about the transport of lipids and the different forms of lipid by which they are being absorbed in the body back to the slides. So, the following what we are basically essentially starting off with is now the lipid transport and distribution if you look at the distribution of lipids they are in different forms and this will come across once again chylomicron very low density lipoprotein then you have intermediate density lipoproteins low density lipoproteins high density lipoproteins at least there are five different forms of lipids which are like five major groups of lipoproteins which are being recognized chylomicron which is a roughly the 95 percent of the weight of chylomicron consist of triglyceride very huge concentration of triglycerides which are present here and chylomicron are the largest lipoprotein ranging basically their diameter may vary from 0.03 micron to 0.5 micron. So, this is the dia of the chylomicrons very low density lipoproteins contain triglyceride manufactured by liver plus the small amount of phospholipids and cholesterol this is what the very low density lipoproteins we are talking about intermediate density lipoproteins are pretty much intermediate in size with respect to very low density lipoprotein and low density lipoproteins and they contain a smaller amount of triglyceride than very low density lipoproteins and relatively more phospholipids and cholesterol than low density lipoproteins. This is pretty much we are talking about very low density lipoprotein and intermediate density lipoproteins then we are talking about these ones which are low density lipoproteins they contain cholesterol and lesser amount of phospholipids and then we have the high density lipoproteins. High density lipoproteins are about 10 nanometer in diameter and they have roughly equal amount of lipids and proteins equal amount of lipids and proteins which are present they are largely cholesterol and phospholipids and their primary function of low high density lipoprotein is transporting excess cholesterol from peripheral issue back to the liver for storage. So, these are the different forms of lipoproteins which are present. So, the liver controls the distribution of other lipoproteins. So, some of the methods what lipids follows in this whole scheme of things that includes. So, basically what is happening is that liver cells are synthesizing very low density lipoproteins for discharging them into the blood vessel that is what liver cells does and in peripheral capillaries lipoprotein lipase removes many triglycerides from very low density lipoproteins and leaving the intermediate density lipoproteins. So, in that process if I have to put it in diagrammatic fashion. So, it will be something like this. So, if this is the liver out here. So, from here the low density lipoproteins are being treated through the blood they are reaching to different peripheral cells. Similarly, the liver cells are being I am just putting cholesterol as C H L cholesterol which is which is released from released from here is being taken by high density lipoproteins and this high density lipoproteins through the blood vessels depuses out and they again come back. Whereas, some of these intermediate density lipoproteins are coming back after blockage of very low density lipoproteins they are broken down and some of the fatty acids are being used for synthesis and where the intermediate density lipoprotein comes back to the liver. So, it is kind of a continuous turnover which is taking place across the liver in that whole process. So, this is something which I wish to highlight. So, if you look at it like what I will request you go through the liver biochemistry that will give you an overall idea how different kind of lipids molecule chylomicrons low density lipoprotein, intermediate density lipoprotein, high density lipoprotein, very low density lipoproteins are being transported synthesized transported and this is critical because whenever there is a liver damage all these things are getting compromised and more and more we are understanding. So, if you look at your blood report it will say high density lipoprotein cholesterol level low density lipoprotein what is good for your heart what is not good for your heart. So, all those things. So, since this is outside the purview of this course. So, I will request you please go through any pick up any in standard textbook and in biochemistry and go through how these different lipids are being synthesized. So, I give you an kind of a rough idea about it, but it will be good if you refer to it those of few who are interested to learn more about these different lipoproteins and the chylomicrons and everything. So, from here I will move on to the proteins which is the tail piece which is left. So, synthesis of amino acid catabolism and anabolism. So, here also I will give you certain terms which I expect you guys to I will give you a brief idea about them, but then I again I expect you to go through some standard textbook of biology or biochemistry mostly you know to understand in depth about all these things especially the enzymes involved in the catabolism process anabolism process of amino acid. So, getting back to the side. So, we are into now protein anabolism and catabolism protein. So, essentially we are talking about amino acids now the smaller unit of individual unit of protein. So, some of the catabolic processes. So, we are into catabolism represent we see catabolism. So, one of the processes is transamination. What is transamination? Transamination is basically attachment of the amino group of an amino acid to a keto acid. So, transamination is a process where attaches the amino acid and attaches the sorry amino group of an amino acid to a keto acid that is called transamination. So, if I have to show it for little bit of your understanding. So, here is the C alpha of amino acid, carboxylic acid sorry O H here you have the hydrogen here you have the N H 2 and here you have the functional group which is R group C H 2 C H 2 and say C 2 and O H. So, this is basically a example of glutamic acid this glutamic acid plus a keto acid. So, what is the keto acid? So, here is the ketone group and here you have the C H 2 attached to a benzene ring. So, here is the keto acid. So, this is the part of the keto acid now during a reaction of transamination which is taken carried out by transaminase enzyme. So, trans means it is transferring what you essentially get after this is C double bonded with O and here you have C H 2 C H 2 C O H. So, this has moved here. So, this becomes a keto acid 2 this considered as keto acid 1 plus what is left. So, this you see this functional group out here this R which is present the R group. Now, this R group here is intact C H 2 and this R group is now attached to this R group is attached to amino group out here and the hydrogen attached here and. So, this becomes a tyrosine. So, this whole reaction where there is a transfer or exchange is false under transamination. This is one of the route by which amino acids are getting degraded there is another route which is called deamination deamination means you are moving the amine group. So, we talk about transamination where you are transferring the now we are talking about the deamination. Let us talk about what is deamination deamination is essentially is performed in preparing an amino acid for breakdown by T C H cycle. So, you are preparing an amino acid. So, as to be broken down in the T C H cycle. Now, what is deamination then. So, deamination again let us take this simple example. So, you have this C H 2. So, I am writing a glutamic acid residue now we have the alpha carbon amino group hydrogen here your carboxylic acid. Now, this glutamic acid in the presence of an enzyme called deaminase is forming. So, of course, taking H 2 O and this needs N A D N A D H N A D is getting reduced to N A D H and in that process something will get oxidized. So, what you are essentially getting is O H and O C H 2 C H 2 O H plus ammonium ion which is N H 4 plus. This N H 4 plus then become part of the T C H cycle which we will show in the next slide what is happening this N H 3 or ammonia plus carbon dioxide which is coming from tricarboxylic acid cycle. So, you are entering inside the T C H cycle now and output is which is nothing but urea or this is the urea cycle. So, if you go back to the previous cycle just I am missing upon it. So, we talked about the transamination here we are talking about the transamination we are talking about the deamination here if you see the deamination. So, it is forming the ammonium ion out here this ammonium ion become eventually forms urea through T C H cycle. So, this is what is happening. So, this is essentially is the process by which the amino acid molecule amino acids are getting degraded and becoming being removed from the body. So, if you take a very protein rich diet on all likelihood your urein will have lot more urea as compared to or uric acid as compared to a person who takes lesser amount of protein in the diet. So, these are the clues. So, next comes after this is the protein synthesis. So, protein synthesis basically is happening in the ribosomes where basically all the proteins are being synthesized by the body through a process of amination which attaches an amino group to a keto group by just by the reverse process. So, there are other ways there is basically an amination taking place where basically a amination attaches an amino group to a keto group. This is an important step in synthesis of non-essential amino acids. So, if I had to give you a overall outline of this whole process. So, it is something like that carb, proteins, lipids. Then you have this amino acid. This triglyceride. You have this glycosine to glucose. Again these are all proteins, amino acids and all these are in that whole process this glucose is forming pyruvic acid. I am just putting it by P a and that is entering into the into the mitochondria for the T C A cycle where acetyl coenzyme A. These amino acids are also you know in both ways and here you have the T C A cycle. From here you have the electron transport chain and here through different routes either through glycerol which is coming from as the product of glycolysis. These glycerols and here the fatty acids becoming part of forming acetyl coenzyme A and become part of the T C A cycle and there is this ATP synthesis which is taking place. So, this is the overall scheme of things whenever we talk about the metabolism. So, they all eventually feed into the mitochondria, but the electron transport chain plays a critical role the reutilization of ATP is there is a formation of ATP is the net gain is that at the end of the day we have higher energy production which helps up to helps us to grow and survive and all the intermediate eventually becomes part of this T C A cycle and that is very essential because otherwise a body cannot have you know think of it a body cannot have several units processing several things. So, the chemistry is very simple they want it to bring it down to a common intermediate some common intermediate through which a common cycle can run instead of having multiple different cycles all over the place at different organelles which is kind of very cumbersome. So, this is the overall idea of the of this whole lipid protein carbohydrate metabolism now we will briefly talk about some of the absorptive process and the thermo regulation process. So, basically this is what is happening and if you look at some of the absorptive processes what is happening. So, in the blood stream you have lipids. So, this is all in the blood. So, you have the lipids you have amino acids you have glucose where they are getting stored. So, lipids are getting stored in adipose tissue and skeletal muscle whereas, amino acids is in pretty much in all tissues everybody needs proteins and glucose all tissues except skeletal muscle except this is an exception except skeletal muscle and other than that it is in the liver and skeletal muscle this is where it goes and talking about distributed in blood stream. So, how these are post absorptive phase how these are distributed from the liver through different processes you have the ketone bodies then liver you have the glucose then from adipose tissue you have the lipids then you have the skeletal muscle you have amino acids and lactic acid and they are all part of the blood stream out here and the destinations are all tissues glucose goes to mostly to the neural tissue lipids for all tissues except the neural tissue and you have then the amino acids going to the liver lactic acids also going to the liver. So, this is pretty much is the overall distribution of this different kind of tissues in terms of their in terms of their post absorptive phase. Now, from here we will move briefly about the thermo regulation. So, talking about thermo regulation. So, the body has to continuously just like it has to maintain an electrolyte balance body has to continuously maintain optimal temperature for all the biochemical processes to take place and body has different mode by which the heat is getting transferred into the body outside the body inside the body a basic thumb rules remains the same we enumerate all the different processes by which body is doing. So, the mechanisms of heat transfer of the body they are basically the very fundamental ones conduction convection and evaporation and within the brain there are the different centers which are actually involved in the regulation of heat gain and heat loss. So, there are different heat gain and heat loss centers which functions at the higher center of the brain which regulates the body to either lose heat and it can lose it in the form of lot of perspiration because you are sweating a lot you are losing heat or you may you know cover yourself with something you are conserving heat. So, there are different modus operandi of the brain higher centers of the brain by which all this thermo regulation processes are being coordinated, but they are coordinated by all the higher centers of the brain they are not coordinated they are indeed they are executed at the local level, but they are kind of controlled at the higher centers. So, let us talk about some of those out here. So, mechanism of increasing heat loss how you can do. So, mechanism of say for example, you want to lose heat what all the process are there. So, the first process is that inhibition of the vasomotor center causing peripheral vasodilation causes peripheral vasodilation and warm blood flows to the surface of body and the output of this is something like this the skin becomes reddish and skin temperature rises and radiation and convective losses increases. So, that is how you are losing second is that as the blood flows to the skin the sweat glands is stimulated the secretion of secretion of the output blood flow to the skin and sweat glands. So, you are basically losing heat. So, there is a third way you are stimulating the respiratory centers of the brain you are basically stimulating them once you are stimulating them there is the depth of respiration increases depth of respiration increases and what happens under such situation is that often an individual begins to respite through open mouth rather than through the nasal pathway. So, basically what you are doing instead of you do start taking it from the mouth and that process you. So, if you see after you finish a kind of marathon or you know law or running you start doing like this you are trying to lose heat because the body is fairly heated up because you have done a lot of exercise. So, this is that is the third way. So, these are very common pathways you look at the skin there is red is it becomes almost red and you slowly start losing it or you know there are mucous glands which start become hyper functional. So, this is how the way you lose it now let us talk about the reverse situation how you are gaining heat into the system. So, mechanism of promoting heat gain promoting I am just putting heat as promoting heat gain in the body how you are doing. So, there is something called shivering thermogenesis what is shivering. So, when you are shivering in a cold night you are essentially what you are doing your muscles are like you know moving like. So, we do like that. So, this is basically what you are doing you are increasing the muscle movement in order to you know you are increasing the heat shivering is a reaction by which you increase the heat of the body specially suppose it is a very chilled cold night and you are really feeling cold. So, your body needs to generate heat in order to protect itself this is how you protect yourself by shivering action. So, this is one of the mechanism by which it is being done. So, there is there are other things which are called non shivering thermogenesis. So, non shivering thermogenesis are regulated by something like pyrotrophin releasing hormone and there are these are being regulated by sympathetic innervation. So, there are several ways by which you really can regulate all these things there may be sympathetic innervation there are other hormonal pathways which could take care of your hormones which are taking care of your heat gain process. So, shivering is the most easiest one, but there are non shivering ways by where the body specially the thyroid hormones play as a critical role someone feels like you know the secretion of hormone which is again regulated by the higher centers of the brain. And in that whole process of shivering non shivering or loss of heat you are involved in all kind of catabolic pathways end of the day it is all this catabolic and anabolic pathways who are the final molecular executor of the action. So, this is how overall the metabolism and thermo regulation is being regulated in our body. So, please go through some of the standard text book on biochemistry to understand the metabolism that will help you. So, thanks a lot thanks for your attention.