Lecture 7 CSF Harvesting energy 2024.pdf

https://xvivo.com/examples/powering-the-cell-mitochondria-2/?fwp_animations=medical-education-animation ATP synthase https://xvivo.com/examples/powering-the-cell-mitochondria-2/?fwp_animations=medical-education-animation Recap Lecture 6….. Recap Lecture 6 continued….. Lecture 7: Harvesting Chemical...

https://xvivo.com/examples/powering-the-cell-mitochondria-2/?fwp_animations=medical-education-animation ATP synthase https://xvivo.com/examples/powering-the-cell-mitochondria-2/?fwp_animations=medical-education-animation Recap Lecture 6….. Recap Lecture 6 continued….. Lecture 7: Harvesting Chemical Energy - Cellular Respiration At the end of this lecture, you should be able to: 1. Describe the processes involved in the generation of ATP from the breakdown of a glucose molecule, including an overall description of the processes, where those processes occur, and the net number of ATP molecules produced per glucose molecule broken down. 2. Understand the difference between substrate-level phosphorylation and oxidative phosphorylation and how the electron transfer chain builds a proton gradient across the inner mitochondrial membrane to generate ATP. 3. Be able to describe the roles of insulin and glucagon in the body, and how these contribute to blood sugar levels. 4. Describe the fundamental pathology of Diabetes Mellitus. Mitochondria – the ATP factory ATP powers cellular work – it is our energy currency The hydrolysis of ATP to ADP and inorganic phosphate releases energy Objective One Many cellular processes require energy in the form of ATP ie. they are not spontaneous e.g. cilia beating Lecture 2 ATP cycle: the transfer of energy between complex and simple molecules in the body, with ATP as the mediator Objective One Fuel is needed to generate ATP Our major categories of fuel: Carbohydrates: broken down to simple sugars Proteins: broken down to amino acids Fats: broken down to simple fats Which are then absorbed Oxygen Dietary Foods (e.g., glucose) CELLULAR RESPIRATION Recyclable Parts Carbon Dioxide Water ATP we focus only on cellular respiration and glucose for BIOSCI 107 Objective One The fate of glucose… Glucose in Food/ Intestines Glucose in Bloodstream facilitated by Insulin Into a Cell Cellular Respiration Cellular Work facilitated by Glucagon Storage for Harder Times (glucose cross-linked together, called glycogen, in liver and skeletal muscle) Objective One Cellular respiration: the controlled release of energy from organic compounds to produce ATP Conversion of glucose to ATP is due to 4 main steps: 1. Glycolysis 2. Pyruvate oxidation 3. Citric acid cycle (or Krebs cycle) 4. Electron transport chain The simplest overview: Objective One Where does cellular respiration occur? cytosol in the matrix across inner membrane Objective One Step 1: Glycolysis invests and produces ATP – but not much Occurs in the cytosol and oxygen is not required two ATP are invested The lysis of glucose to produce two pyruvate molecules four ATP are produced two ATP and 2NADH are produced (net) NADH is an electron carrier later in the electron transport chain There are 10 steps in the conversion of glucose to pyruvate – you don’t need to know them for 107 You also do not need to be able to write or balance these chemical equations Objective One Step 2: Pyruvate oxidation to form Acetyl CoA This step links glycolysis to the citric acid cycle Occurs in the mitochondrial matrix and oxygen IS required produces no ATP, but produces 1 NADH per pyruvate (or 2 per glucose) plus 1 CO2 The 2 carbon Acetyl CoA molecule is able to enter the citric acid cycle Objective One Step 3: Citric acid cycle (simplified) There are multiple steps within here to achieve this! for this course you don’t need to know them Occurs in the mitochondrial matrix Results in : 2 ATP 6 NADH 2 FADH2 4 CO2 (per glucose molecule) Requires oxygen – it is an aerobic process FADH2 and NADH are electron donors in the electron transport chain Objective One Citric acid cycle intermediates are used in other metabolic pathways Details are not examinable, but the concept of intermediates is important We are complex! Acetyl CoA amino acid synthesis fatty acid synthesis Oxaloacetate gluconeogenesis Citrate Malate α-Keto-glutarate a series of reactions: product of one reaction is the substrate for the next amino acid synthesis neurotransmitter Succinyl CoA the citric acid cycle completes the extraction of energy from glucose Objectives 1&2 So, what have we made so far………. Glycolysis produces 2 net ATP per glucose Pyruvate oxidation produces no ATP Citric acid cycle produces 2 ATP per glucose Substrate phosphorylation : ATP generated by direct transfer (from a substrate) of a phosphate group to ADP Glycolysis and Citric acid cycle make ATP via substrate phosphorylation Oxidative phosphorylation: ATP is generated from the oxidation of NADH and FADH2 and the subsequent transfer of electrons and pumping of protons Objectives 1&2 Step 4: the Electron Transport Chain Occurs at proteins within the inner membrane Requires oxygen – it is an aerobic process NADH and FADH2 are oxidized to donate electrons Electrons transfer from protein-to-protein along the chain in a series of redox reactions At each transfer, each electron gives up a small amount of energy which enables H+ ions to be pumped into the intermembrane space Oxygen “pulls” the electrons down the chain, and is then the final electron acceptor where it is reduced to water NADH and FADH2 from Glycolysis and the Citric acid cycle are used here Objectives 1&2 Step 4 continued: Chemiosmosis The hydrogen ions in the intermembrane space rush down their concentration gradient (chemiosmosis) through ATP synthase. This causes the “turbine” within ATP synthase to turn The rotation of the ATP synthase turbine enables the phosphorylation of ADP to generate ATP This results in the production of 26 or 28 ATP (per glucose) Objectives 1&2 Step 4: ETC and chemiosmosis = oxidative phosphorylation This is much more efficient than substrate phosphorylation the bulk of ATP production occurs here “fall” of electrons down the chain enables movement of H+ ions into intermembrane space and generates a proton gradient which “drives” the ATP synthase turbine Oxygen is required oxygen is the final electron acceptor – cyanide blocks passage of electrons to O2=death of cell Objectives 1&2 Putting the steps together : cellular respiration Details of video are examinable BioFLIX Cellular Respiration animation, 4m:28s long - is on our CANVAS page: https://canvas.auckland.ac.nz/courses/71549/pages/02-cell-structure-and-function?module_item_id=1321709 ~10 million ATPs produced per second in one cell via cellular respiration!! In your course guide p59 After some revision, aim to be able to fill this in without needing your notes at all (note, older Tortora editions (13th) states higher ATP numbers, please use the values shown above) Objectives 1, 2 & 3 Cellular respiration is versatile We can derive energy from more than just glucose Fats, proteins and more complex carbohydrates generate ATP also This is enough detail for 107 Campbells Fig 9.18, page 184 Monomers enter glycolysis and the citric acid cycle at different points Objectives 1, 2 & 3 Control of cellular respiration Phosphofructokinase is the “gate-keeper” for glycolysis; it catalyses step 3 – where glucolysis becomes irreversable inhibited by citrate and ATP ie. products of cellular respiration Campbells Fig 9.19, page 185 stimulated by AMP AMP accumulates when ATP is being used rapidly Objective Three Homeostasis of blood glucose hyperglycemia Fasting ~4-6 mmol/L hypoglycemia Homeostasis : the maintenance of relatively constant conditions within physiologically tolerable limits Objective Three Insulin and Glucagon Insulin: Produced by beta cells of Islets of Langerhans in pancreas Function: promote glucose uptake into cells (for ATP production or storage in liver) Glucagon: Produced by alpha cells of Islets of Langerhans in pancreas Function: Stimulates the breakdown of glycogen to increase blood sugar levels Objectives 3&4 What happens if you lose the function of insulin? No glucose in cells No ATP from glucose No glycogen stored for harder times Diabetes Mellitus : the ability to produce or respond to the hormone insulin is impaired results in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood ≥7mmol/L fasting https://commons.wikimedia.org/wiki/File%3A3D_medical_animation_still_of_Diabetes.jpg Objective Four Lack of functional insulin = Diabetes Mellitus Type 1 or insulin-dependent diabetes: https://www.diabetes.org.nz Body does not produce insulin, as beta cells of pancreas are destroyed, often this is autoimmune, or genetic or through environmental factors Affects 5 – 10 % of diabetics, and onset usually occurs in children or adolescents. Requires insulin replacement Type 2 or non-insulin-dependent diabetes: Body produces insulin, but receptors are non functional (insulin resistance) Most (>90%) diabetics are Type II, usually adults over the age of 40 Can be linked to other pathologies and obesity Objective Four Contradictory symptoms? Diabetes mellitus is caused by a lack of functional insulin. As a result, levels of glucose in the blood build up, well beyond normal homeostatic limits. Increased blood glucose alters the volume and osmolarity of blood, with subsequent pathological consequences. More about blood osmolarity in Module 4, and in Lab 3 Two of the symptoms of this disease are: significantly increased hunger There are many other symptoms and effects of Diabetes Mellitus significant weight loss – you do not need to know them for 107 These two symptoms seem to be in opposition to each other: if the patient is constantly hungry and eating, why would they then lose weight? Some useful resources for this lecture Your textbook readings, listed in the course guide with each lecture Pearson BioFlix movie 4.5 minutes - within CANVAS for this module Self-directed (ie. we don’t provide answers) study questions are in the lecture guide Complete the table on page 54 as part of your revision, and practice completing the empty diagram about 2 minutes long https://xvivo.com/examples/powering-the-cell-mitochondria-2/?fwp_animations=medical-education-animation Publisher permission was granted for lecture slide use of images/resources from the 107 texts (Tortora and Campbell). Unless otherwise stated content was sourced from these texts or were lecturers own Next CSF lecture: Cell Communication Tip: try to watch the simple 1-minute video on my Canvas Module BEFORE Lecture 8