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Transcript
PBL 8 – NIGHT STARVATION 1999 Paper 3, Part F: Q6 Digestive Cycle Mouth-SI CHO in diet: Starch, lactose & sucrose are the 3 main sources. Also small amounts of others, including alcohol, glycogen, lactic acid, dextrins. Cellulose is starch we eat but is not digested. Salivary amylase begins hydrolysis of CHO in the mouth. In stomach, the low pH stops digestion. Digestion continues in the small intestine from pancreatic amylase. The amylase breaks down starch to maltose (diasaccharide), maltotriose (trisacch) and dextrins. The disaccharides are further hydrolysed to monosacchardes by the brush border enzymes on the intestinal epithelium (enzymes are Lactase, maltase and sucrase). Lactose (by lactase) glucose + galactose Maltose (by maltase) glucose + glucose Sucrose (by sucrase) glucose + fructose Dextrins (by dextrinase) small glucose polymers & monosaccharides. Thus, all the final products are monosaccharides. They are taken up by Na-coupled transporter (facilitated diffusion) on the luminal side of the enterocytes, then glucose diffuses into the portal blood via a GLUT-2 transorter on the basolateral side of the enterocytes. Galactose is handled in the same way. Fructose is usually converted to glucose within the enterocytes, then absorbed as per glucose. 2000 Paper 1, Part A: Q1-2, 4-6 A hiker is lost in the Kosciusko ranges for 14 days without food, but with access to water. When rescued, he is weak but alert. Question 1. (2 marks) What is the major metabolic process responsible for the maintenance of blood glucose concentrations (a) 12 hours after the last meal? Glycogenolysis which has kicked in after 4-6 hours (b) 3 days after the last meal? Gluconeogenesis is in full flight from the liver. Other tissues are now using ketones as a fuel Question 2. (9 marks) (a) Explain in what form glucose is stored in the liver, adipose tissue and muscle in the fed state (3 marks) In the fed state, glucose is stored as glycogen within the liver and muscle. It is stored in this state by conversion of glucose to G-6-P and is then joined together into the the highly branched glycogen state. In adipose tissue it is converted into acetyl-CoA and then stored as FA's and TAGS. (b) State whether energy stores in these organs can be used to maintain blood glucose concentrations during fasting, and if not, explain why (3 marks) Liver glycogen can be degraded into glucose and released into the blood to maintain BGL. Muscle glycogen is broken down the glucose but cannot exit the cells into circulation. TAG's undergo Beta oxidation to produce acetyl CoA and ketone bodies; neither of which can be converted into glucose. (c) Explain the effects of insulin on pathways of glucose metabolism in the liver. (3 marks) Insulin directly affects glucose metabolism in the liver. It achieves this by activating phosphofructokinase which will cause phosphorylation of fructose 1 P to F-1,6-P, and it will also upregulate other enzymes like pyruvate kinase which will convert pyruvate into acetyl CoA to be used as an energy source for the TCA cycle. Question 4. (5 marks) Organs such as the liver use fatty acid oxidation to meet most of their energy requirements during fasting. Outline the changes in metabolic regulation that occur during fasting, to promote fatty acid mobilization in adipose tissue, and oxidation in the liver. During fasting, insulin levels will fall to minimal levels due to a decreasing glucose concentration. This decrease in insulin will stop glucose uptake by insulin-mediated uptake into adipose tissues. Subsequently, the decreasing levels of circulating glucose will cause an increase in the levels of glucagon, which will upregulate lipolysis in the adipose tissues. In an insulin dominant state, the levels of malonyl CoA are high and this inhibits the carnitine acyl transporter 1. With low insulin this inhibition is negated and FAs can be uptaken by the hepatic cells. Here, beta-oxidation will occur, creating large amounts of acetyl CoA to be oxidised and used as an energy source. NB: Stops uptake of TAGs into the adipose and the glucose uptake is downreg. Question 5. (6 marks) With the aid of a diagram/s, illustrate how energy derived from the oxidation of fatty acids is used to drive ATP synthesis. Energy yield from Beta oxn. is high and each removal of a C-C yields 1 FADH2 & 1NADH & ATP from TCA. Ketone bodies are usually only in a very low concentration in blood. During fasting, its concentration increases to provide energy to peripheral tissues. KB -> A CoA -> TCA Question 6. (4 marks) Explain how an increase in ATP demand (for example to drive gluconeogenesis) results in an increase in O2 consumption. With an increase in ATP demand, there is an increase in O2 consumption because of an increased need to retain an electric gradient across the inner mitochondrial membrane. When ATP is made at a faster rate, H+ will be shuttled through the 5th ATPase bound membrane protein at a faster rate, resulting in increased H+ concentration within the cell. If this was allowed to continue, there would eventually be an equalising of the electrostatic charge across the membrane, leading to no further H+'s travelling through the ATPase bound protein. Increased O2 will take up and bind these H+'s and remove them from the inner membrane, allowing the electric gradient to be maintained. 2003 Paper 2, Part 2: Q2-4 Question 2. (10 marks) In the fed state, excess carbohydrate is stored as fat. Draw a simple diagram to illustrate how glucose in the liver is converted to fat that is transported to, and ultimately stored in adipose tissue. Question 3. (10 marks) With the aid of a diagram, illustrate how energy derived from the oxidation of NADH in the electron transport chain is used to drive ATP synthesis. Question 4. (8 marks) Organs such as the liver use fatty acid oxidation to meet most of their energy requirements during fasting. Outline the changes in metabolic regulation that occur to promote fatty acid mobilization and oxidation in fasting. 2005 Paper 1: Part A: Q3, 4 Question 3. (10 marks) In the fed state, excess carbohydrate is stored as fat. Draw a simple diagram to illustrate the process in which glucose is converted to fat in the liver, and then transported to, and ultimately stored in, adipose tissue. Question 4. (8 marks) Organs such as the liver use fatty acid oxidation to meet most of their energy requirements during fasting. Outline the changes in metabolic regulation that occur to promote fatty acid mobilization and oxidation in fasting. 2005 Paper 2, Part C: Q1 A 25 year man (Mr Peter D) is found unconscious by his wife in the garage of their house. He was slumped over the steering wheel. The engine of the car was running. He has been brought in by the Ambulance Service to the Emergency Department of the local hospital. Question 1. (10 marks) Below is a list of conditions that can lead to coma in any person. For each, state the underlying mechanism responsible. Condition Diabetes Carbon monoxide Poisoning Renal Failure Head Injury Heart Failure Mechanism Decrease in glucose, brain runs out of energy to stay active Decreased oxygen in blood, brain is affected Blood is full of unwanted substances, not cleared properly, affects heart, and brain Haemorrhage causing ischaemia in brain Decreased blood to brain