Metabolism Notes PDF

Metabolism – Notes 2025-02-14 9:19 AM Lecture 1: Metabolism: Metabolism is all chemical reaction occurring in body Metabolism is the sum of:...

Metabolism – Notes 2025-02-14 9:19 AM Lecture 1: Metabolism: Metabolism is all chemical reaction occurring in body Metabolism is the sum of: 1. Catabolism 2. Anabolism 1. Catabolism Breakdown complex molecules into simpler ones Exergonic – reactions release energy stored in the molecules Catabolism in the cell required for: Converting substrates to a 2-carbon molecule - utilized by mitochondria to produce ATP 2. Anabolism Combine simple molecules into complex ones Endergonic – requires energy Anabolism in the cell required for: Replacing membranes, organelles, enzymes, and structural proteins Cellular catabolism or aerobic metabolism or cellular respiration Requires oxygen Occurs in the mitochondria 40% of energy is captured Used to convert adenosine diphosphate (ADP) to adenosine triphosphate (ATP) ATP is used for anabolism and other cellular functions 60% of energy escapes as heat Warms the interior of the cell and the surrounding tissue ATP Adenosine Triphosphate (ATP) "energy currency" of the body The energy stored in this molecule is found within the bonds between each phosphate group ATP is created in exergonic reactions and used in endergonic reactions ADP + P + energy ↔ ATP Catabolic reactions created ATP: Example – glycolysis Anabolic reactions require energy: Example – glycogenesis Utilization of Nutrients Comes from the diet and from reserves Reserves are mobilized when absorption across the digestive tract is insufficient to maintain normal nutrient levels Liver cells break down triglycerides and glycogen – fatty acids and glucose can be released Adipocytes break down triglycerides – fatty acids can be released Skeletal muscle cells break down contractile proteins – amino acids can be released We can use all of these reserves to create ATP Restoration of Nutrient Reserves Reserves are stocked when absorption by the digestive tract is greater than immediate nutrient needs Liver cells store triglycerides and glycogen Adipocytes convert excess fatty acids to triglycerides Skeletal muscles build glycogen reserves and use amino acids to increase numbers of myofibrils Utilization of Resources Cells in most tissues continuously absorb and catabolize glucose Nervous tissue must have a continuous supply of glucose During starvation, other tissues can shift to fatty acid or amino acid catabolism - conserves body's glucose for nervous tissue - can also use ketones REDOX Reactions: These two are ALWAYS paired Oxidation OIL – Oxidation is Loss Removal of electrons from a molecule Decrease in potential energy Typically involves a loss of hydrogen atoms, also called dehydrogenation reactions Reduction RIG – Reduction is Gain Addition of electrons to a molecule Increase in potential energy Coenzymes When a molecule is oxidized, it often loses electrons (in the form of hydrogen atoms) These liberated hydrogen atoms have to go somewhere (something must be reduced) 2 common coenzymes used are: 1. NAD – NAD+ is reduced to NADH+ H+ 2. FAD – FAD is reduced to FADH2 You will be able to create more ATP with these coenzymes – they are NOT proteins When we start talking about glucose metabolism, the process involves the oxidation of glucose Glucose is C6H12O6 During glycolysis it is split into 2 pyruvate molecules Pyruvate is C3H4O3 Therefore, we have lost 4 hydrogen atoms Where do they go? They are accepted by NAD+ which becomes NADH/H+ Mechanisms of ATP Generation: 1. Substrate-level Phosphorylation Transferring of a high-energy phosphate group from an intermediate directly to ADP Examples: Glycolysis Citric acid cycle Phosphocreatine 2. Oxidative Phosphorylation Remove electrons and pass them through electron transport chain to oxygen Carbohydrate Metabolism: Remember glucose? Breakdown product of carbohydrate that is absorbed in the small intestine Glucose is the preferred source of energy, most other saccharide are converted to glucose Why is Glucose Preferred? Glucose is a small, soluble molecule that is easily distributed through body fluids Glucose can provide ATP anaerobically (without oxygen) through glycolysis Glucose can be stored as glycogen, which forms compact, insoluble granules Glucose can be easily mobilized because the breakdown of glycogen (glycogenolysis) occurs very quickly Mobilization of other intracellular reserves involves much more complex pathways and takes considerably more time GluT Transporters GluT transporters bring glucose into the cell via facilitated diffusion Insulin causes expression of more of these transporters in the plasma membrane, increasing rate of entry into cells Glucose is trapped in cells after being phosphorylated Fate of Glucose Fate of glucose depends on needs of body cells 1. ATP production – always first step If energy is needed immediately 2. Glycogen synthesis Combining hundreds to thousands of glucose molecules to form glycogen – stored form of glucose 3. Synthesis of amino acids Used to form proteins 4. Triglyceride synthesis – always last step When other body stores are full, the remaining glucose is converted to fats Cellular Respiration There are 4 steps in the complete utilization of a glucose molecule – glucose catabolism 1. Glycolysis 2. Formation of acetyl coenzyme A 3. Citric Acid Cycle reactions – kreb's cycle 4. Electron transport chain reactions 1. Glycolysis Anaerobic respiration – does not require oxygen Substrate-level phosphorylation 2. Formation of acetyl coenzyme A Aerobic respiration – requires oxygen 3. Citric Acid Cycle reactions Kreb's Cycle Substrate-level phosphorylation 4. Electron transport chain reactions Aerobic respiration – required oxygen "oxidative phosphorylation" Glycolysis: Cellular respiration begins with glycolysis – First step Begins with – 1 glucose molecule Splits 6-carbon glucose into two 3-carbon molecules of pyruvic acid Occurs in – cytosol 10 reactions Consumes 2 ATP but generates 4 ⇒ NET GAIN of 2 ATP 2 NADH First 5 septs uses the ATP and increases the potential energy in the molecules Steps 6 – 10 is where 4 ATP are generated Phosphofructokinase Rate-limiting step The rate limiting step is the slowest (irreversible) step in a pathway Determines how fast the whole pathway can be carried out Drives the rate limiting/rate determining step 1. How does glucose enter the cell? Through GLUT transporters via facilitated diffusion End Products From one glucose molecule 2 pyruvate molecules 2. What happens once glucose enters the cell? 4 ATP molecules – net 2 ATP It is phosphorylated right away, which traps it in the cell 2 NADH If oxygen is available, will go to ETC to create more ATP 3. What is the starting molecule in glycolysis? 1 glucose molecule What Happens to Pyruvate? 4. What is the end product of glycolysis? Fate of pyruvic acid depends on oxygen availability 2 pyruvate molecules If oxygen is scarce (anaerobic), it is reduced to lactic acid 5. What is the net gain of ATP? If oxygen is plentiful (aerobic), pyruvic acid is converted to acetyl coenzyme A and it enters the Citric Acid Cycle 2 ATP – produces 4 but uses 2 Formation of Acetyl Coenzyme A: Oxygen is plentiful – aerobic The second step in cellular respiration Transitional step between glycolysis and Krebs cycle Each pyruvic acid is converted to 2-carbon acetyl group – remove one molecule of CO2 as a waste product Pyruvic acid enters the mitochondria first and then is converted to acetyl coenzyme A Each pyruvic acid also loses 2 hydrogen atoms - NAD + reduced to NADH/H+ Occurs in mitochondrial matrix Pyruvate Dehydrogenase Breaks apart to create 2 CO2 and 2 NADH By products per glucose molecule: 2 CO2 – waste product 2 NADH – will go to ETC to create more ATP The Cori Cycle: Oxygen is scarce – anaerobic If oxygen is scarce, it is reduced to lactic acid 2 pyruvic acid + 2NADH + 2H+ → 2 Lactic acid and 2 NAD+ Once lactic acid is produced, it quickly diffuses out of the cell and enters the blood Hepatocytes can convert lactic acid to glucose Other oxygenated tissue can reduce the lactic acid back into pyruvate, where it will then be used 1. What happens to pyruvic acid in an anaerobic environment? In anaerobic conditions Reduced to form lactic acid which diffuses into the blood where it travels to liver Can replenish glucose to be used for substrate level phosphorylation 2. What happens to pyruvic acid in an aerobic state? Not sustainable – net loss Converted to Acetyl CoA to enter the CAC The Citric Acid Cycle: 3. Where is acetyl CoA formed? Mitochondrial matrix Also known as Kreb's Cycle or TCA Cycle The third step of cellular respiration 4. What is the overall purpose of the Citric Acid Cycle? The reduced coenzymes that carry potential energy (NADH and FADH2) Requires oxygen – aerobic respiration Occurs – in matrix of mitochondria 5. What happens to the CO2 produced in the Citric Acid Cycle? Diffuse out of mitochondria, out of the plasma membrane, into the blood where it is transported to the Series of redox reactions that transfer energy to coenzymes Overall function is to remove hydrogen atoms from specific organic molecules and transfer them to coenzymes lungs to be exhaled End Products 2 CO2 ( 4 CO2 per glucose molecule) Waste product 3 NADH ( 6 NADH per glucose molecule) Will go to ETC to create more ATP 1 FADH2 ( 2 FADH2 per glucose molecule) Will go to ETC to create more ATP 1 ATP ( 2 ATP per glucose molecule) Electron Transport Chain (ETC): Series of electron carriers called cytochromes in inner mitochondrial membrane Receive electrons from NADH and FADH2 Each electron carrier is reduced or oxidized as it passes along electrons down the chain O2 is the final electron acceptor The side of oxidative phosphorylation Overview Each electron carrier has an increased infinity for electrons as we move down the chain As electrons are passed from one carrier to another, energy is released Energy is used to pump H+ ions into intermembrane space Energy stored in electrochemical gradient is used to create ATP Final electron acceptor is O2 and water is formed Produces more than 90% of ATP used in the body Lack of oxygen stops the ETC Blocking cytochromes also stops the ETC Example – poisons such as cyanide With no functioning ETC, the citric acid cycle stops Cells die from lack of ATP Proton-motive force – is the gradient Chemiosmosis – movement of hydrogen back into the matrix ATP synthase – uses the movement of energy to generate ATP Bound to inner mitochondrial membrane Summary NADH FADH2 ATP Glycolysis 2 N/A 2 Formation of Acetyl CoA 2 N/A N/A Citric Acid Cycle 6 2 2 TOTAL 10 2 4 32 ATP per glucose molecule