Cell Respiration and Metabolism - EXS 112 L4 PDF

Cell Respiration and Metabolism General Objectives Define the term glycolysis. Explain why there is a net gain of 2 ATP in this process. List the initial substrates and final products of anaerobic metabolism. Explain the physiological significance of the lactic acid pathway. Explain...

Cell Respiration and Metabolism General Objectives Define the term glycolysis. Explain why there is a net gain of 2 ATP in this process. List the initial substrates and final products of anaerobic metabolism. Explain the physiological significance of the lactic acid pathway. Explain the process of aerobic respiration. List final products for each step. Explain how glucose and glycogen can be interconverted. Define the term gluconeogenesis and explain the Cori Cycle. Explain the metabolic pathway by which glucose can be converted to fat. Define the terms lipolysis and B-oxidation. Include how fat can be used for energy. Describe transamination and explain its functional significance. List the different sources of energy that cells use. Base terminology(1) Synthesis Generally refers to the creation or the formation of a compound i.e. Glycogen synthesis, Fatty acid synthesis Genesis Refers to the birth or starting point of a compound i.e. Gluconeogenesis (making sugar) Lysis Refers to the breakdown of compounds i.e. cellular lysis (cell breaks apart), glycolysis (sugar breakdown) Base terminology(2) Metabolism has two subsets: Anabolism or Anabolic The process of creating compounds or the storing of energy i.e. making muscles or tissues or converting carbohydrates into storage form Catabolism or Catabolic The process of breaking down tissues or energy stores i.e. convert carbohydrate storage into energy or muscle loss due to starvation Respiration and Metabolism Respiration and Metabolism Respiration: Process of oxygen intake and carbon dioxide removal Metabolism: Chemical reactions that involve energy transformation Example: Oxygen enters lungs, diffuses into blood Cells use oxygen in metabolic reactions (oxidation-reduction) Metabolic reactions produce carbon dioxide CO2 re-enters blood > Returns to lungs > Diffuses across alveolar membrane to be expelled Metabolism Types of metabolism: Anabolism – requires input of energy Synthesis of large molecules: glycogen, fats, proteins Catabolism – releases energy Frees energy for ATP production Lysis of glucose, fatty acids, amino acids Catabolism drives anabolism Involves oxidation-reduction reactions Transfer of electrons from initial molecule to intermediates and then to final electron acceptor Producing ATP(1) ATP = Adenosine diphosphate (ADP) + Inorganic phosphate (Pi) Unlike glucose molecules, ATP can be used directly by cells for energy Energy stored in phosphate bond Producing ATP(2) Producing ATP in the presence of oxygen: Aerobic respiration Net gain of ~38 ATP Oxygen = final electron acceptor Producing ATP without oxygen: Anaerobic metabolism Net gain of 2 ATP Both start the same Glycolysis: glucose splitting Producing ATP(3) Before we start. Where do we GET the glucose? Sources of glucose: Digestive tract Carbohydrates broken down into absorbable units (e.g., glucose) Liver Glycogenolysis Breakdown of glycogen to glucose Gluconeogenesis Formation of glucose from: Amino acids Fat byproducts Ex) glycerol  START: Glucose in blood plasma NEXT: Enters cell by passing through plasma membrane NEXT: Glycolysis occurs in Without Oxygen: cytoplasm for both 1) 2) processes 1) Aerobic respiration With Oxygen: continues in mitochondria 2) Anaerobic 3) 2) metabolism occurs in cytoplasm Aerobic Cell Respiration Aerobic Cell Respiration: Enzymatically-catalyzed steps 1) Glycolysis 2) Citric acid (Krebs) cycle 3) Oxidative phosphorylation / Electron transport chain Oxygen = final electron acceptor Releases carbon dioxide and water Results in net gain of ~38 ATP Anaerobic Cell Respiration Anaerobic Metabolism: Occurs after glycolysis step, without oxygen Organic molecule = final electron receiver Converts pyruvic acid into lactic acid Can then later be used for aerobic respiration Results in net gain of 2 ATP (from glycolysis) Metabolic Pathways Why glucose is key for producing energy Step 1 - Glycolysis 1 C6H12O6 (glucose) à 2 C3H4O3 (pyruvic acid) Glycolysis: Breaking apart glucose 1. First we’re going to need 2 ATP molecules 2. ATP is used to phosphorylate a glucose molecule 1. Phosphorylation: The process of adding phosphate to a target 3. After adding two phosphates to glucose 1. By product is two ADP molecules 4. Enzymes then break glucose into two 3-carbon molecules 1. Glucose is originally a 6-carbon molecule 5. Each molecule then gains another phosphate 6. These double phosphate molecules interact with one NAD and two ADP to create one NADH and two ATP 7. The resulting molecule is now pyruvate 8. Note** = Since one glucose creates two 3-carbon molecules, steps 5 – 7 happen twice per glucose Overall Input: One glucose, two ATP, two NAD Output: Two pyruvates, four ATPs, two NADH Net gain is two ATP and one NADH Step 1.5 – Preparation What happens to Pyruvate? It moves to the mitochondria to be a part of the Citric Acid cycle Mitochondria is where a lot of oxygen/CO2 reactions occur Preparing for the Citric Acid Cycle Pyruvate interacts with NAD to form Acetic Acid One carbon gets lost as CO2 and NAD becomes NADH The acetic acid combines with Coenzyme A (CoA) to form Acetyl-CoA Acetyl-CoA is a 2-carbon molecule that is necessary for the Citric Acid Cycle Step 2 – The Citric Acid Cycle The Citric Acid Cycle (TCA, Krebs) Acetyl-CoA interacts with Oxaloacetic Acid to create the 6-carbon Citric Acid Acetyl-CoA (2 carbons) and Oxaloacetic Acid is (4 carbons) Why is Citric Acid important? It acts as a main intermediate for several pathways Reactions with Citric Acid produces several key energy molecules Three NADH, one FADH2 and 1 ATP FADH2 is important for future pathways Citric Acid is also recyclable! It can be converted back to Oxaloacetic Acid for future reactions Key thing to note is this conversion ends up producing two molecules of CO2 Step 3 – Aerobic Respiration While we’re still in the mitochondria… Electron Transport Chain Where NADH and FADH2 produce energy Redox Time: NADH and FADH2 serve as Reducing Agents NADH and FADH NAD+ and FAD+ Step 3 – Aerobic Respiration ETC involving NADH and FADH2 produces NAD and FAD Both can be recycled back in TCA or even glycolysis What happens to the electrons/H+? The electrons pass through a series of proteins found in the mitochondria Each passage creates a H+ gradient that is used to drive ATP Synthase ATP Synthase The final step in the ETC or Oxidative Phosphorylation The Hydrogen gradient combined with Oxygen and ADP results in the production of ATP and water Triggered by electrons being transferred to Oxygen Net result? Why is cyanide dangerous? About 28 molecules of ATP per glucose sugar It targets oxidative phosphorylation by preventing the ETC and shutting down ATP production Anaerobic Metabolism: Absence of Oxygen(1) So what happens if you have no oxygen? Your body has anaerobic pathways in addition to aerobic pathways Lactic Acid Pathway Glycolysis proceeds normally, but Pyruvate gets converted into Lactic Acid The NADH generated during glycolysis gets used up to form lactic acid Net result? Not much. Only the two ATP gained from glycolysis. The NADH generated ends up lost Anaerobic Metabolism: Absence of Oxygen(2) Not an efficient way to utilize glucose nor generate ATP Drawback of some cells not having mitochondria or access to aerobic respiration i.e. red blood cells Importance of oxygen supplies Muscles don’t have oxygen and buildup excess lactic acid Potential for ischemia Example: Myocardial Ischemia Clogged arteries means plaque buildup Plaque buildup deters blood/oxygen flow Heart and muscles aren’t about to generate energy for contraction Additionally, plaques can break off causing thrombosis (clots) or heart attacks ATP Overview From one glucose molecule: Anaerobic metabolism = 2 ATP Aerobic respiration = ~38 ATP (30-32 re-enter cytoplasm) Food + oxygen à Aerobic ATP production Application: During exercise, breathe harder & faster Body using oxygen and sugar faster than usual Producing more ATP and more CO2 Often use ATP faster than oxygen is brought in If necessary, temporary use of anaerobic metabolism for ATP Sore muscles after intense exercise = build up of lactic acid Glucose, Lactic Acid, and Glycogen Glycogen Excess glucose cant be maintained by the cell Too much osmotic pressure Instead the body stores glucose as glycogen Chains of condensed glucose molecules i.e. how cells compact DNA into chromosomes Glycogenesis: Formation of chains of phosphorylated glucose or glucose 6-phosphate (G6P) around an anchor protein Glycogen is essentially a polysaccharide Glycogenolysis: The reverse process – breaking down G6P for glycolysis Commonly occurs in skeletal muscles and the liver Except only the liver actually release glucose into the blood Lactic Acid and the Cori Cycle What happens if there is too much lactic acid buildup? Muscle cells can send lactic acid to be processed by the liver Gluconeogenesis: A process that is performed in the liver that create glucose from non-carbohydrate sources Lactic Acid à Pyruvic Acid/Pyruvate à Glucose-6-Phosphate à Glycogen or Glucose Free glucose can be sent from the liver back to the muscle for more energy Cori Cycle: The transport of glucose from liver to muscle What about Lipids and Proteins? Metabolism of fats and peptides Metabolism of Lipids What if there is excess ATP? The body cannot store excess ATP Excess food energy causes ATP production to stop i.e negative feedback Liver can synthesize molecules for storage Returning back to Pyruvate and Acetyl-CoA What if ATP production is inhibited? Glycolysis is halted and no pyruvate formation Instead, the Acetyl-CoA gets used to create: cholesterol, ketones, and fatty acids Lipogenesis: formation of fat Combination of fatty acids and carbohydrates 3 fatty acids + 1 glycerol = triglycerides Stored in adipocytes Glycerol?? Lipogenesis: formation of fat 3 fatty acids + 1 glycerol = triglycerides Stored in adipocytes Where did this glycerol come from? It gets created when the 6-carbon glucose gets split into 3-carbon molecules One of them is Glycerol Adipose/Adipocytes Adipose or adipocytes are fat cells Cells that contain bundles of fats White Adipose Tissue (there’s also brown) Tryglyceride storage Remember that energy is stored in bonds and is not destroyed Lipolysis Breakdown of tryglycerides into fatty acids and glycerol Glycerol can re-enter glycolysis to either become glucose or further into the Citric Acid cycle B-oxidation The breakdown of fatty acids into Acetyl-CoA Excess Lipid Metabolism The balance between triglyceride synthesis and breakdown Lipolysis is normally more efficient than B-oxidation of fatty acids Results in excess fatty acids that are waiting to be processed So what happens? The body makes ketones! Ketone Bodies/Ketosis Water-soluble compounds that circulate in the blood Made from fatty acids/Acetyl-CoA and acetone Alternative pathway to produce energy in the event of low glucose Usually kicks in during starvation, dieting or diabetes However… Excessive ketones causes build up in the blood and ketones are acidic Results in ketoacidosis Recall that low blood pH is fatal What about this keto diet? Protein Metabolism Metabolism of Protein(1) Protein is composed of amino acids and peptides which can be used for energy Amino acids are characterized by an amine/nitrogen group Remove the nitrogen and the rest can be converted into glucose or fatty acids There are 20 relevant amino acids, but the body can’t make 8 out of the 20 The 8 amino acids are the essential amino acids and must come from outside sources The other 12 can be created as long as you have the essentials and some carbohydrates (Yeah, you still need carbs) Metabolism of Protein(2) Transamination: The process of transferring an amine/nitrogen group to a target molecule Common for synthesizing amino acids Seen in pathways involving Pyruvate/Pyruvic acid, citric acid, and ketone bodies Metabolism of Protein(3) What happens to the amine/nitrogen groups? Consuming proteins and metabolizing them results in an increased nitrogen concentration in the body Normally this will be processed and secreted as urea Hydration is key for increased protein consumption Nitrogen Balance Maintaining the balance of ingested and excreted nitrogen Nitrogen is reactive and can be deadly if unchecked in excess Children want a positive balance of nitrogen for growth Conversely, malnutrition means your excreting more than ingesting Since the nitrogen didn’t come from food, then it must have been sourced from your muscles Metabolism of Protein(4) How does nitrogen find its way into your urine? Oxidative Deamination The process of removing amine/nitrogen groups from an amino acid Produces two compounds: keto acid and glutamic acid Glutamic Acid then transfers that amine to CO2 to form Urea What’s a “Keto Acid”? General term for intermediates in the Citric Acid cycle If you go to the bathroom a lot, that just means you are making energy! Energy Sources Different organs have different purposes and Energy sources compared energy sources Fat = 9 calories per gram Liver à glucose stores and ketone bodies Carbohydrates = 4 calories Adipose à tryglycerides and fatty acids Proteins = 4 calories Ketones = 4 calories Muscles à lactic acid and amino acids Remember, not all sources are The body prefers to spread energy sources processed the same nor do they across multiple organs process at the same efficiency Prevents the depletion of one source while maximizing the resource it needs the most i.e. the brain prefers to use glucose and can pull it from the blood or liver or, if needed, even use ketones