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Cellular respiration Cellular respiration is a kind of catabolic reaction by wich chemical bond energy of organic molecule is released as ATP, the fuel used by all living things and heat energy. Cellular respiration is braking down glucose (sugars) wich are made in process of photosynthesis. There are two main types of cellular respiration 1. Aerobic-when oxygen is present 2. Anaerobic where there is no oxygen present Aerobic cellular respiration: C6H12O6 + 6 O2 → 6 CO2 + 6 H2O +38 ATP There are four main steps in aerobic respiration: 1. Glycolysis is a series of enzyme catalyzed reaction by which glucose molecule is converted into two molecules of pyruvate. The products are NADH, ATP, and pyruvate. NADH and ATP are two form of chemical energy that is going to put in one “energy bank”. There also create something what we called pyruvate. Pyruvate will be reactant in next step aerobic cellular respiration. In glycolysis we use 2ATP and we create 4ATP. 2. Pyruvate oxidation-pyruvic acid that is produced in glycoysis diffuses across double membrane of a mitochondrion and enters in mitochondrion matrix. When pyruvic acid enters into mitochondrial matrix, it reacts with a molecule called coenzyme A to form acetyl CoA. CO2, NADH are produced in this reaction. 3. Krebs cycle- reactant is acetyl CoA. Acetyl CoA will be degraded to produce ATP, CO2, FADH2, and NADH. Krebs cycle occurs in the matrix of mitochondrion. This step doesn’t require any ATP. So we don’t have to invest any ATP but we create 2ATP. 4. Electron transport system (ETS)- the reactants are NADH and FADH2 which are created in Krebs cycle. In this cycle we created more ATP. The final product is water. The reason why we create water is O2. Oxygen will accept two electrons and create water. Here bulk of ATP is created- 34 molecules of ATP. 1 1. Glycolysis Is a series of enzyme catalyzed reaction Glycolysis starts with 1. 2. 3. 4. 5. glucose. There are two phases in glycolysis. Preparatory (investment) phases – it is called investment because it uses 2ATP. By the end of these phases two molecules of ATP have been consumed in the production of 2 molecules of PGAL from one glucose molecule. Phosphorylation of glucose – this step requires investment of one ATP molecule. The addition of a phosphate group on the 6 carbon is catalyzed by enzyme hexokinase. Conversion of Glucose-6-Phosphate into Fructose-6-Phosphate Phosphorylation of Fructose-6-Phosphate into Fructose-1,6-Diphosphate. Fructose-6-phosphate is phosphorylated by addition of a second phosphate group, this time to the 1 st carbon of the fructose molecule. Another ATP molecule is consumed in this reaction. Cleavage of Fructose-1,6-Diphosphate: Fructose-1,6-Diphosphate is cleaved by enzyme aldase to produce two molecule containing 3 carbon atom and one phosphate group. One is Glyceraldehyde-3-Phosphate (PGAL), the other is dihydroxyaceton phosphate Conversion of Dihydroxyaceton phosphate into PGAL. 2 1. 2. 3. 4. 5. Payoff phase – PGAL enter in payoff phase. Chemical bonds are broken NAD pick up electron and hydrogen ions forming NADH. The energy is released to produce ATP. Oxidation of Glyceraldehyde 3-phosphate 1,3 diphosphoglycerate: glyceraldehide 3- phosphate is converted in1,3 diphosphoglycerate by addition of inorganic phosphate and removal of hydrogen. The hydrogen molecules are then accepted by NAD and two molecules of NADH are synthesized. Synthesis of ATP from 1,3 diphosphoglycerate: The phosphate on the 1st carbon of the 1,3 diphosphoglycerate molecule is transferred to ADP. Thus two molecules of ATP are synthetised. Conversion of 3-phosphoglycerate to 2-phosphoglicerate:the number - prefix before the name of the molecule indicates the position of the phosphate group. Ex. 3-phosphoglycerate has a phosphate group attached on 3rd carbon phosphoglycerate molecule. Removal water from 2-Phosphoglycerate: two molecules water are synthesized from molecule phosphoglycerate with gain two molecule phosphoenolpyruvate. Synthesis ATP from phosphoenolpyruvate. The product of these reactions is pyruvate. 3 Explanation of process glycolysis: There are two phases of glycolysis. One, I call them investment phase because uses 2 ATP. C-C-C-C-C-C glucose ↓2ATP P-C-C-C-C-C-C-P And than I am essentially going to break up the glucose into two molecules containing 3carbon compound. P-C-C-C C-C-C-P Pyruvate Pyruvate They have phosphate group on them. The phosphate group comes from these ATPs. This is called PGAL or phosphoglyceraldehyde. So we use 2ATPs. That’s why called investment phase is. Each of these PGAL can go in payoff phase and each of these PGAL can turn into pyruvate which is another 3-carbon. Payoff phase: when we go from PGAL to pyruvate we produce two things. Each of these PGAL produces two ATPs and each produce NADH. They start of with raw material NAD and they reduce by adding hydrogen. NAD is reduced in NADH and later these NADH are used in ETC to produce ATPs. Net of glycolysis is 2ATPs, 2NADH, and 2 pyruvate molecules. 4 2. Pyruvate Oxidation The inner compartment of mitochondria is called matrix. But you have these pyruvate and they are quite not ready to enter in Krebs cycle. So there is something like preparation step. We have to oxidize them. Reaction is called pyruvate oxidation and we end up with two carbon compound call Acetyl CoA. We generate something what is two carbon compound and we reduce NADH. Pyruvate is with three carbon atom, but Acetyl CoA is with two carbon atom. One carbon cleavage of and it pick up some O2 and it is released in atmosphere like CO2. 5 3. Krebs cycle Now you have acetyl CoA ready to enter in Crebs cycle. All of these are catalyzed by enzymes. Acetyl CoA merges with oxalacetate wich is four carbon atoms. These two react together and they form Citrate or Citric acid wich is six carbon molecules and Citric acid oxidise to get back to oxalacetate acid (four carbon molecule). Two carbon atom cleavage off and forms CO2. This whole idea is generate ATP, NADH, and FADH2. These are input in ETC. The first “step” citrate is isomerased to isocitrate, oxidized and decarboxylated to form aketoglutarate (5C) yieliding NADH, H and CO2. a-ketoglutarate is converted into succinate (4C) yielding NADH, H, and ATP and CO2. Succinate is converted into fumarate and one molecule FADH2 is produced. Fumarate is converted into malate and molecule of NADH is produced. Maltase is converted into oxalacetate. Neto of Krebs cycle: 6 molecules of NADH, 2molecules of FADH2, and 2ATP. 6 4. ETS (ETC) After we have done with glycolysis and Krebs cycle we have left 10 NADH and 2 FADH2. These are going to be input in ETC in order to generate ATP. Each NADH will be indirectly responsible for the production 3 ATPs, and each FADH2 is going to be responsible for production 2 ATPs. In general NADH gets oxidized (oxidation) losing H ions. NADH → NAD + H + 2e Now these electrons are popping out and they are in very high energy state. They are transported to series transmission molecules. And these electrons when travel from one molecule to another they are going into slightly lower energy state. In the last step of ETC these electrons are used to reduce water. 2e + H + O2→ H2O Every times when electrons go from high to lower energy states, it releases energy. So energy is released when you go from high to low energy state. Energy is used to pump protons across the inner membrane of mitochondria. So energy is released when you go from high to low energy state. Energy is used to pump protons across the inner membrane of mitochondria. Krebs cycle occurs in matrix. So in matrix you have a lot of NADH and FADH2.When they oxidize (lose electrons) to NAD and electrons keep transferring from one molecule to another. As they from high to low energy state they release energy. That energy is used to pump proton (H ions) across membrane of mitochondria into other compartment. But that is not ATP yet. It’s just a gradient where we have a lot of H proton concentration in outer compartment become more acidic than the matrix. So there is electric gradient between outer and inner compartment. These protons are pumped from matrix into outer compartment and they want to get back into the matrix. And that is where ATP is formed. On the end ETC is some protein that is called ATP synthetase. 7 H ions want to back but they can not. The cristae are impermeable to do that. They have to found special way. They are going to beck trough ATP synthetase. ADP molecules are little attached on one part of protein (ATP synthetase). As the protein enter in ATP synthetase they make electrical gradient and the inner axle of ATP synthetase turns and its is going to squeeze ADP and phosphate group together to form actually ATP. So ATP synthetase used this energy from proton gradient to drive axle its essentially pushes these ATP together. 8 Calculation of ATP production: 1NADH= 3 ATPs 1FADH2= 2 ATPs 10 NADH= 30 ATPs 2FADH2= 4 ATPs 2ATP ( glycolysis) + 2 ATP (Krebs cycle) + 34 ( ETS)= 38 ATP The 2 NADH+H from glycolysis are transferred from the cytoplasm to the mitochondria. During their transfer across the mitochondrial membrane, some of their energy is lost. Instead of each NADH+H yielding 3 ATP molecules, during this stage they only produce 2 ATPs. 2ATP ( glycolysis) + 2 ATP (Krebs cycle) + 32 ( ETS)= 36 ATP 9 Catabolism of lipids Digestion converts the foods we eat to a form that the body can use for energy or store for future needs as fat. Digestion is a catalyzed process - chemical reactions take place in the body that would not occur without the presence of catalysts called enzymes. The specific enzymes that operate to catalyze fat digestion are called lipases. A lipid molecule is composed of a glycerol molecule bonded to fatty acid. The first step in lipid metabolism is the hydrolysis of the lipid in the cytoplasm to produce glycerol and fatty acids. In the next step glycerol (3C) is converted into pyruvate (3C) and it goes trough glycolysis pathway to make energy. Excess lipids are stored in adipose tissue. Hormone glucagon stimulates hormone sensitive lipase. It’s help get fatty acid into blood. We have short and long chain fatty acid. Short chain is 6C long and it can easily cross mitochondrial membrane. Long chain is greater than 12C. These require transport mechanism. On both side mitochondrial membrane you have CAT (carantine acyl transferase), and these will help long fatty acid chain to get into mitochondria. Fatty acids are going to enter in process β oxidation. β oxidation just break down carbon chain, clip two carbon on a time. What we do in β oxidation is create Acetyl CoA. Let’s pretend we deal with 16 carbon molecule. C-C-C-C -C-C-C-C- C -C- C-C- -C-C- C-C We have divided them into two, and get eight round. Each 2C is acety CoA. Each section will give us 1 NADH and one FADH2. 10 How many sections? Seven so we have got seven FADH2 and NADH. 8 Acetyl CoA will participate to the Krebs cycle and release 24 NADH and 8 FADH2 an 8 ATP. Totally 31 NADH and 15 FADH2 are produced from breakdown of this fatty acid molecule. This provides a total of 131 ATP molecules from one fatty acid chain when NADH and FADH2 are used in electron transport chain. A lipid contains three fatty acids attached on one glycerol molecule. 3x131 + 19 an ATP molecule from glycerols gives the huge total 412 ATP molecules from the catabolism the single lipid molecule. 11