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PHASE 1 Revision Akanksha Sinha Regina Sarbaratnam

IMMS (2). PHASE 1 Revision Akanksha Sinha Regina Sarbaratnam. The Peer Teaching Society is not liable for false or misleading information…. Aims - Overview. METABOLISM (Carbohydrates, Protein, Lipid, Alcohol, Glycogen) ATP

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PHASE 1 Revision Akanksha Sinha Regina Sarbaratnam

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  1. IMMS (2) PHASE 1 Revision Akanksha Sinha Regina Sarbaratnam The Peer Teaching Society is not liable for false or misleading information…

  2. Aims - Overview • METABOLISM (Carbohydrates, Protein, Lipid, Alcohol, Glycogen) • ATP (ATP-ADP cycle, Glycolysis, Kreb’s cycle, Oxidative Phosphorylation) • FATTY ACID OXIDATION/KETONES (Beta oxidation, Ketogenesis) • ACID/BASE/BUFFER (Henderson-Hasselbach equation) • OXYGEN TOXICITY (ROS, Haber-Weiss and Fenton reactions) • HISTOLOGY (Stains, Epithelia) The Peer Teaching Society is not liable for false or misleading information…

  3. Metabolism The chemical processes that occur within a living organism in order to maintain life The Peer Teaching Society is not liable for false or misleading information…

  4. Metabolism 4 main energy sources: Carbohydrates: Starch, fructose, sucrose, glucose, lactose Mainly come from starchy foods and fruit. Proteins: Largely come from meat ,dairy ,pulses , fish Alcohol: typically ethanol Lipids: triacylglycerols 4kcal/g 4kcal/g 7kcal/g 9kcal/g The Peer Teaching Society is not liable for false or misleading information…

  5. What happens to the excess energy intake? 1. Stored as triglycerides (approximately 15kg) 2. Stored as glycogen (approximately 200g in liver, 150g in muscle) 3. Stored as protein (approximately 6kg) The Peer Teaching Society is not liable for false or misleading information…

  6. BMR Energy needed to stay alive at rest • Increase BMR: • Increased body weight • Hyperthyroidism • Low ambient temperature • Fever/infection • Caffeine/stimulant intake • Pregnancy • Decrease BMR: • Increased age • Being female • Dieting/Starvation • Hypothyroidism The Peer Teaching Society is not liable for false or misleading information…

  7. ATP ATP ‘Adenosine Triphosphate’ Structure components: Adenine, Ribose, 3 Phosphate How does it provide Energy? The Peer Teaching Society is not liable for false or misleading information…

  8. ATP • -The ATP molecule has two phosphoanhydride bonds. • These are RELATIVELY WEAK bonds, hence require relatively less energy to break • Overall more energy is released in forming the products that used to break bonds in the reactants ATP Hydrolysis ADP The Peer Teaching Society is not liable for false or misleading information…

  9. ATP-ADP Cycle CO2 ATP Respiration: Energy production Carbohydrate Lipid Protein Energy utilization: Biosynthesis of macromolecules Muscle contraction Active ion transport Thermogenesis O2 ADP + Pi The Peer Teaching Society is not liable for false or misleading information…

  10. ATP- ways to generate ATP? • Glycolysis • Kreb’s cycle • Oxidative phosphorylation • Substrate level phosphorylation • Via electron transport chain • Beta oxidation (Discussed in fatty acid oxidation) The Peer Teaching Society is not liable for false or misleading information…

  11. Glycolysis • Glycolysis Pathway of 10 steps Takes place in cytoplasm In short – Glucose  2Pyruvate + 2ATP + 2NADH (AEROBIC) 2Lactate + 2ATP (ANAEROBIC) The Peer Teaching Society is not liable for false or misleading information…

  12. Glycolysis Energy Investment Phase - 2 ATP Energy Generation Phase + 4 ATP Glycolysis generates a NET 2 ATP plus 2 NADH The Peer Teaching Society is not liable for false or misleading information…

  13. Step 1 • Facilitated diffusion of Glucose into cell mediated by Insulin • Phosphorylation of Glucose by Hexokinase • -ATP The Peer Teaching Society is not liable for false or misleading information…

  14. Step 2 • Isomerism • G6PF6P The Peer Teaching Society is not liable for false or misleading information…

  15. Step 3** • F6P F1,6BP • Via phosphofructokinase (PFK is primary regulated step of glycolysis; responds to both cellular energy and hormonal regulation) • -ATP The Peer Teaching Society is not liable for false or misleading information…

  16. Step 6-10 • 6: NADH (x2) produced • 7: ATP (x2) produced • 8: • 9: • 10: 2Pyruvate + ATP (x2) produced • Remember all the enzymes • “Good Gracious, Father Franklin Did Go By Picking Pumpkins (to) Prepare Pies Pyruvate enters the TCA cycle The Peer Teaching Society is not liable for false or misleading information…

  17. Acidosis affecting glycolysis • PFK1 is pH dependent • Inhibited in acidosis Control of glycolysis via: • Step 1 • Step 3* -key regulatory step in glycolysis Negative regulators: H+, ATP, Citrate, hormonal Positive regulators: AMP The Peer Teaching Society is not liable for false or misleading information…

  18. Kreb’s/ TCA cycle In Mitochondrial matrix Acetyl CoA can come from glycolysis/ fatty acid breakdown/ amino acids’ carbon skeletons The Peer Teaching Society is not liable for false or misleading information…

  19. Kreb’s/TCA cycle • Inhibited by ATP, NADH, succinyl CoA • Activated by ADP The Peer Teaching Society is not liable for false or misleading information…

  20. Electron Transport Chain • The electron transport chain(ETC) is a process in which the NADH and [FADH2] produced during glycolysis, β-oxidation, and other catabolic processes are oxidized thus releasing energy in the form of ATP. The mechanism by which ATP is formed in the ETC is called chemiosmoticphosphorylation The Peer Teaching Society is not liable for false or misleading information…

  21. The chemiosmotic theory Based on the following: -inner mitochondrial membrane is impermeable to protons, hence the mitochondrial matrix is a closed environment -the proton pumping of the ETC leads to the proton motive force which in turn provides the energy for ATP synthesis (Proton flow through the ATP synthase protein drives ATP synthesis) The Peer Teaching Society is not liable for false or misleading information…

  22. The chemiosmotic theory The Peer Teaching Society is not liable for false or misleading information…

  23. Substrate level phosphorylation • some ATP can be made in the cytoplasm through a process called substrate-level phosphorylation • With this type of phosphorylation you have an adenosine diphosphate (ADP), which is a unit of adenosine attached to two (di) phosphate groups The Peer Teaching Society is not liable for false or misleading information…

  24. oxidative phosphorylation • Oxidative phosphorylationis the metabolic pathway in which the mitochondria in cells use their structure, enzymes, and energy released by the oxidation of nutrients to reform ATP (involves ETC!!!) The Peer Teaching Society is not liable for false or misleading information…

  25. TOTAL ATP • Total ATP made from one molecule of glucose: 34 ATP But this is very debatable • Some sources will say 30 or 32 ATP The Peer Teaching Society is not liable for false or misleading information…

  26. Fatty acid oxidation/ Beta oxidation • Examples of fatty acids: • Palmitoleic acid • Linoleic acid • Palmitic acid The Peer Teaching Society is not liable for false or misleading information…

  27. Fatty acid oxidation/ Beta oxidation Fatty Acid Acetyl CoA (used in TCA/Krebs cycle) The Peer Teaching Society is not liable for false or misleading information…

  28. Fatty acid oxidation/ Beta oxidation ATP PPi Fatty Acid Acyl adenylate The Peer Teaching Society is not liable for false or misleading information…

  29. Fatty acid oxidation/ Beta oxidation CoA AMP Acyl adenylate Acyl CoA Acyl CoA synthetase The Peer Teaching Society is not liable for false or misleading information…

  30. Fatty acid oxidation/ Beta oxidation The carnitine shuttle !!! The Peer Teaching Society is not liable for false or misleading information…

  31. The Carnitine Shuttle Carnitine CoA Acyl CoA Acyl Carnitine Carnitine Acyl Transferase I The Peer Teaching Society is not liable for false or misleading information…

  32. Inner mitochondrial membrane CoA Carnitine Acyl Carnitine Acyl CoA Carnitine Acyl Transferase II The Peer Teaching Society is not liable for false or misleading information…

  33. Fatty acid oxidation/ Beta oxidation Acetyl CoA Acyl CoA Acyl CoA – 2C • Sequential removal of 2- carbon units • Each round of β-oxidation produces: • 1 mole of NADH • 1 mole of FADH2 • 1 mole of acetyl-CoA The Peer Teaching Society is not liable for false or misleading information…

  34. Ketogenesis The process by which ketone bodies are produced as a result of fatty acid breakdown. Ketones are used for energy at low fat states. The Peer Teaching Society is not liable for false or misleading information…

  35. Ketogenesis 2 Acetyl-CoA CoA-SH thiolase Acetoacetyl-CoA Acetyl-CoA + H20 HMG-CoA synthase CoA-SH HMG-CoA HMG-CoA lyase Acetyl-CoA Acetoacetate Acetone β- hydroxybutyrate The Peer Teaching Society is not liable for false or misleading information…

  36. I know, no pathology … Diabetic ketoacidosis • Reduced supply of glucose due to a significant decline in circulating insulin and an associated increased in circulating glucagon. • The increased production of Acetyl-CoA leads to ketone body production • This lowers the pH of the blood The Peer Teaching Society is not liable for false or misleading information…

  37. Acid/Base/Buffer • Acid = proton (H+) donor HA ⇔ H+ + A- • Base = proton (H+) acceptor B + H+ ⇔ BH+ • Buffer = weak acids or bases that act to maintain H+ concentration The Peer Teaching Society is not liable for false or misleading information…

  38. Acid/base/buffer • Acidosis can either be respiratory or metabolic • Alkalosis can either be respiratory or metabolic • pH range is 7.35-7.45. But ideal pH is 7.4 • Compensation: metabolic is slow, respiratory is fast. The Peer Teaching Society is not liable for false or misleading information…

  39. Henderson-Hasselbalch equation • Henderson’s formula:- [H+ ] x [HCO3 - ] = K x pCO2 • Hasselbalch converted it to pH pH = pK + log ([HCO3 - ] / [CO2]) The Peer Teaching Society is not liable for false or misleading information…

  40. Acidosis • Respiratory • Insufficient ventilation retains CO2 so there is more carbonic acid in the blood leading to acidosis • Causes include COPD (chronic bronchitis + emphysema), asthma Carbonic anhydrase • Metabolic • Low bicarbonate levels leading to acidosis • Causes include bicarbonate losses from the GI tract e.g. diarrhoea, DKA, lactic acidosis (anaerobic respiration), renal failure The Peer Teaching Society is not liable for false or misleading information…

  41. Alkalosis • Respiratory • Blowing off too much CO2 leading to alkalosis • Causes hyperventilation, pink puffers COPD (i.e. type 1 respiratory failure), anxiety, fever • Metabolic • Loss of H+ or too much bicarbonate leading to alkalosis • gastric secretions contain large quantities of hydrogen ions. • Causes include excess vomiting (because you’re losing H+), pyloric stenosis, anorexia nervosa, ingestion of bicarbonate The Peer Teaching Society is not liable for false or misleading information…

  42. Anion Gap The anion gap is calculated by subtracting the serum concentrations of ANIONS (Cl- and HCO3-) from the concentrations of CATIONS (Na+ and K+) BUT potassium concentrations, being very low, usually have little effect on the calculated gap. This leaves the following equation: Anion gap = [Na+] − ([Cl−] + [HCO3−]) =16 meq/lit The magnitude of this difference (i.e., "gap") in the serum is often calculated when attempting to identify the cause of metabolic acidosis. If the gap is greater than normal, then high anion gap metabolic acidosis is diagnosed (due to increased cation: H+) The Peer Teaching Society is not liable for false or misleading information…

  43. Types of Buffer systems • Proteins (51%) • Weak acid/base groups • Bicarbonate (43%) • CO2 removed via lungs, Bicarbonate regenerated by kidneys • Haemoglobin (6%) • Deoxy Hb binds H+  HHb + Bicarbonate • Amine group on Deoxy Hb bind CO2 carbaminohaemoglobin  Most important Haemoglobin binds both CO2 and H+ and so is a powerful buffer The Peer Teaching Society is not liable for false or misleading information…

  44. Oxygen Toxicity Toxic reactive oxygen derivatives with: • Free radicals • Unpaired electrons in outer shell • High reactivity OR DEF: Chemically reactive molecules with unpaired electrons in outer shell & free radicals (unpaired electron) derived from oxygen The Peer Teaching Society is not liable for false or misleading information…

  45. Formation of ROS e-, 2H+ e- O2 Oxygen H2O2 Hydrogen peroxide O2 Superoxide Generates radicals with transition metals (Fenton or Haber Weiss rx) Produced by ETC e-, H+ e-, H+ OH• + H2O H2O Hydroxyl radical The Peer Teaching Society is not liable for false or misleading information…

  46. ROS OH• (hydroxyl radical) • Most potent radical • Lipid soluble • Chain reaction forms lipid peroxides & organic radicals H202 (hydrogen peroxide) • Not actually a radical • Oxidising agent in presence of Fe2+ or other transition metals • Generates hydroxyl radical • Lipid soluble The Peer Teaching Society is not liable for false or misleading information…

  47. Formation of hydroxyl radical Fenton reaction Haber-Weiss reaction - O2 H2O2 + + H2O2 Fe2+ H+ O2 Fe3+ + + H2O OH• + + OH• OH- The Peer Teaching Society is not liable for false or misleading information…

  48. Production of ROS • Endogenous • natural by-product of O2 metabolism • Produced mainly inside cell organelles ie. (mitochondria) • Exogenous • UV radiation, smoking, inflammation The Peer Teaching Society is not liable for false or misleading information…

  49. +ve ROS • Respiratory bursts • ROS released during phagocytosis of bacteria • Damages bacterial cell membrane • Fenton’s reaction • O2  O2-H2O2+Fe2+Fe3+ + OH- + OH• The Peer Teaching Society is not liable for false or misleading information…

  50. -ve ROS • Cellular damage • Damage to membranes of nucleus, mitochondria, endoplasmic reticulum & cell • Increased permeability leads to influx of calcium, water & sodium The Peer Teaching Society is not liable for false or misleading information…

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