8131MED - Metabolism feeding and fasting_2024 - final lecture notes 290124.pdf

Metabolism feeding and fasting Sandra Ramos [email protected] Learning Outcome Outline the effect of feeding and fasting on metabolism. Include alterations in the insulin:glucagon ratio and its metabolic effect, fuel sources for major tissues and any storage molecules formed in each state. Nut...

Metabolism feeding and fasting Sandra Ramos [email protected] Learning Outcome Outline the effect of feeding and fasting on metabolism. Include alterations in the insulin:glucagon ratio and its metabolic effect, fuel sources for major tissues and any storage molecules formed in each state. Nutrient pool Nutrient pool can be drawn upon to meet body’s energy need Carbohydrate Fat Amino acid Linked through interconvertible processes involving key intermediates Acetyl CoA Glycolysis CAC Control of Metabolism Metabolic controls act to equalise blood concentrations of energy sources between two nutritional states. 1. Fed State – Absorptive State During and shortly after eating Nutrients provided by GIT Anabolism exceeds Catabolism 2. Fasting State – Post absorptive state Between meals Nutrients provided by the breakdown of stored nutrients Catabolism exceeds Anabolism Metabolic balance Primary purpose is glucose homeostasis. –Glucose must be maintained at 3.9 –5.8 mM Controlled by the balance of two main hormones: –Insulin –Glucagon Alteration in the release is dependent upon glucose concentrations Fed state Anabolism exceeds catabolism Glucose is the major fuel Dietary fats and amino acids are used to recycle body protein and fat with a small amount of oxidised for energy Excess glucose, protein and fat are converted to fat for storage Insulin Hypoglycaemic hormone Inhibits key enzymes of Gluconeogenesis in the liver Increase glucose oxidation Increase glycogen synthesis, fat synthesis and protein synthesis Fasting state Catabolism exceeds Anabolism Initially catabolise Glycogen – Glycogenolysis Catabolise Fatty Acids and Protein to generate intermediates for gluconeogenesis (making new glucose) Primary Goal – MAINTENANCE of BLOOD GLUCOSE Glucagon Increase glycogenolysis Increase gluconeogenesis Increase ketogenesis Decrease glycogen synthesis Decrease glycolysis Increase fatty acid mobilization Sources of blood glucose Glycogenolysis Liver– first line of glucose reserve can maintain blood sugar for 4 hours Skeletal muscle – lacks enzyme to dephosphorylate glucose and release into the blood Lypolysis Adipose tissue – breakdown of fat to yield fatty acids and glycerol Liver – glycerol produced from triglyceride breakdown is used by the liver to produce glucose (gluconeogenesis) Protein catabolism Major substrate for gluconeogenesis Neural control Sympathetic nervous system also involved in control of glucose homeostasis – In response to a sudden drop in blood glucose Exercise, fight or flight (stress, injury or anxiety) Epinephrine/adrenaline Released by adrenal medulla in response to sympathetic activation Acts on liver, skeletal muscle and adipose tissue Mobilises substrates so we can deal with stress Actions essentially the same as glucagon Mobilise fat Promote glycogenolysis Starvation vs fasting Glucagon elevated ++ Fatty acids mobilised and degraded faster than acetylCoA usage Excess acetyl-CoA converted to ketones (liver) released as fuel Production rises until ~10 days of fasting, when meets nervous system’s energy needs As ketone rises, the pH lowers, ketones spill into urine Body proteins are sacrificed as gluconeogenic precursors Suppression of appetite - ketosis eventually leads to loss of appetite Ketone body formation Ketone bodies include: –Acetoacetate –D-β-hydroxybutyrate –Acetone Synthesis occurs when fat oxidation is increased resulting in an accumulation of Acetyl CoA –Fasting –Starvation –High fat or protein diet Enzymes for synthesis are located mainly in the mitochondria of the liver Allow tissue protein conservation during starvation periods Prolonged fasting Hormonal control of metabolism The synthesis of complex molecules, by using simple precursors of smaller units, is called: A. Catabolism B. Anabolism C. Amphibolism D. Ketogenesis E. Degradation The concentration of lactate in blood plasma before, during and after a 400-m sprint are shown below. [Lactate] What causes the rapid rise in lactate concentration? What causes the decline in lactate level after the run? List the metabolic pathways involved Before run Run After run The concentration of lactate in blood plasma before, during and after a 400-m sprint are shown below. What causes the rapid rise in lactate concentration? Anaerobic glycolysis converting pyruvate to lactate. What causes the decline in lactate level after the run? List the metabolic pathways involved The concentration of lactate in blood plasma before, during and after a 400-m sprint are shown below. What causes the rapid rise in lactate concentration? Anaerobic glycolysis converting pyruvate to lactate. What causes the decline in lactate level after the run? List the metabolic pathways involved The Cori cycle: lactate converted back to pyruvate Gluconeogenesis: utilising pyruvate to produce glucose and replace glycogen Which of the following mammalian cells is unable to aerobically metabolize glucose to carbon dioxide? A. Hepatocytes B. RBC C. WBC D.Muscle cells E. Reticulocytes The citric acid cycle produces which of the following? A. NADH B. FADH2 C. ATP D. All of the above How many of each? 6 NADH, 2 FADH and 2 ATP Gluconeogenesis is the production of glucose from noncarbohydrate molecules. Which of the following is not substrate for gluconeogenesis? A. Lactate B. Alanine C. Glycerol D. Acetyl CoA E. Propionyl CoA Which statements are True regarding the ETC? Lack of ADP and Pi acceptor will stop ETC O2 is essential as terminal electron acceptor Lack of NAD and FAD will stop ETC Uncoupling of ETC will disrupt the chemiosmotic gradient Which of the following hormone decreases blood glucose and increases the uptake of glucose in various tissues like skeletal muscle, adipose tissues? A. Glucagon B. Epinephrine C. Cortisol D. Insulin E. Growth hormone Link the terms to the right description B 1 - The synthesis of glucose from lactate, glycerol, or amino acids B. Gluconeogenesis F 2 - The synthesis of glycogen from glucose C. Glycogenolysis D D. Lipogenesis 3 - The synthesis of triacylglycerol from fatty acids and glycerol C 4 - The process of breaking down glycogen A 5 - The process of breaking down triacylglycerol into free fatty acids and glycerol E 6 - The synthesis of ketone bodies from acetyl CoA A. Lipolysis E. Ketogenesis F. Glycogenesis Which of the following statements is TRUE? A. Glycolysis occurs stimulated by Glucagon B. Glycolysis occurs in mitochondria C. Glycolysis occurs in the presence and absence of oxygen D. Glycolysis occurs when ATP concentration is high The chemiosmotic hypothesis involves all of the following except: A. A membrane impermeable to protons B. Electron transport by the respiratory chain pumps protons to the intermembrane space of the mitochondria C. Proton flow into mitochondria depends on the presence of ADP and Pi D. ATPase activity is reversible E. Only proton transport is strictly regulated, other positively charged ions can diffuse freely across the mitochondrial membrane Which of the following is a 6 C molecule? A. Oxaloacetate B. Succinate C. Acetyl CoA D. Citrate E. Pyruvate During electron transport, protons are pumped out of the mitochondrion at each of the major sites except for: A. Complex I B. Complex II C. Complex III D.Complex IV Complete the sentences: Glycogenolysis can be stimulated by the hormones Glucagon & Epinephrine Non-hormonally, the accumulation of AMP , or low energy level, which indicates low levels of ATP Glycogenolysis Regulation Hormonal inhibition of glycogen synthase Glucagon Epinephrine (muscle) Non hormonal Low energy = Accumulation of AMP Stimulates glycogen phosphorylase b Increases glycogen breakdown What are the fates of pyruvate?