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Questions: 1. Glucose can be metabolised through glycolysis, the citric acid cycle and oxidative phosphorylation to produce energy for the body in the form of ATP.a. Calculate the net number of ATP that can be generated from four (4) moles of glucose in the liver. Assume that this is occurring under optimal conditions. Show all workings.b. Would the same number of ATP be produced if the four molecules of glucose were being metabolised in the muscle tissue? How many ATP would be generated? Please explain.2. Diabetes mellitus is a chronic condition in which the levels of glucose in the blood are too high. Blood glucose levels are normally regulated by the hormone insulin, which is made by the -cells of the pancreas.a. Discuss why a person with diabetes mellitus might have fruity smelling breath.b. If they have elevated blood glucose levels, why is the body not able to use this glucose?c. Can a healthy individual produce ketones? Explain your answer.3. The metabolism of protein is influenced by wh ether the body is in a fed or fasted state. Prolonged fasting will also affect metabolism differently from the short fasting periods between meals.a. What is the typical metabolic fate of protein that has just been consumed?b. How does protein metabolism differ during fasting? Discuss how the metabolism of protein changes as fasting becomes more prolonged.c. Vegetarians and vegans are often encouraged to combine complementary sources of protein (e.g. legumes and grains) in a meal. Why might this be recommended?d. It is now thought that protein combining in one meal is no longer necessary, as long as complementary proteins are consumed at some time throughout the day. Why is this?4. The Citric Acid Cycle and Oxidative Phosphorylationa. Discuss the importance of the citric acid cycle in macronutrient metabolism.b. Why is GTP considered to be the equivalent of ATP? c. Explain how one molecule of acetyl CoA entering the citric acid cycle produces 12 molecules of ATP in the liver (please show all workings) Answers: 1. (a): The complete metabolism of glucose includes its processing through phosphorylation in cytosolic glycolysis until oxidation in tricarboxylic acid cycle. The glucose molecule converted to glucose-6-phoshate consuming one molecule of ATP under the influence of enzyme hexokinase. The glucose-6- phosphate molecule further transforms to fructose-6-phosphate under the influence of phosphoglucoisomerase. Furthermore, fructose-6-phosphate consumes one ATP under the influence of phosphofructokinase to reveal fructose-1,6-biphosphatase and an ADP molecule. The fructose-1,6-biphosphatase metabolized to dihydroxyacetone phosphate and glyceraldehyde phosphate by the mediation of aldolaze enzyme. The dihydroxyacetone phosphate transformed to glyceraldehyde phosphate, resulting in net production of its 2-molecules that further react with triose phosphate dehydrogenase enzyme to produce 1,3-bisphosphoglycerate (2-molecules) that assimilate with phosphoglycerokinase and 2 ADP to lead 3-phospho glycerate and two molecules of ATP. Indeed, both molecules of 3-phosphoglycerate combine with phosphoglyceromutase to produce 2 phosphoglycerate that further react with enolase enzyme to produce phosphoenolpyruvic acid (2 molecules) with the elimination of a water molecule. Finally, PEP associates with two molecules of ADP under the influence of pyruvate kinase to form pyruvate (2 molecules) with the production of 2 ATPs (Peet, 2013:p.396). The pyruvate further undergoes oxidation through TCA cycle and electron transport chain to yield 36 molecules of ATP for single mole of glucose. C6H12O6 + 6O2 + 36Pi + 36ADP + 36H+ 6CO2 + 36ATP + 42H20 Therefore, 4-moles of glucose after complete aerobic oxidative metabolism in liver would produce approximately 144 (= 4 x 36) molecules of ATP. (b): The metabolism of glucose in muscle tissue follows the anaerobic glycolysis in context to the ATP production. The incomplete oxidation of glucose in muscle tissue leads to the formation of lactic acid under the influence of lactate dehydrogenase, resulting in the formation of 2 molecules of ATP from a single molecule of glucose (Lodish et al, 2000). Therefore, the net production of 8 ATP molecules (= 4 x 2) achieved from four molecules of glucose under the process of anaerobic metabolism of glucose in muscle tissue. 2. (a): The patients with diabetic ketoacidosis experience fruity smelling breath following lack of nourishment and episodes of abdominal pain and vomiting. Indeed, the excessive vomiting in diabetic ketoacidosis results in removal of acetone, thereby resulting in fruity order indicating the defect in fatty metabolism (Springhouse, 2008:p. 54). (b): The diabetic patients with high blood glucose levels are unable to utilize the additional glucose due to the increased insulin resistance, thereby resulting in the episodes of hyperglycaemia (Ranson, 2007:p.191). Indeed, the increased production of glucose in liver cells attributes to the glucose intolerance by hepatocytes under the influence of impaired insulin metabolism and disrupted insulin sensitivity associated with the beta cells dysfunction (Goldstein Muller-Wieland, 2007:p.13-14). (c): The clinical literature reveals the formation of ketone bodies in healthy people with a concentration of 1 milligram per 100 millilitres in human blood (Satake 2003, pp. 316-317). This production of ketone bodies in trace amount is the normal physiological process in healthy individuals attributing to the production of acetoacetic acid and processing of tricarboxylic acid cycle. 3. (a): The immediate metabolic fate of protein based on its conversion to amino acids under the influence of pancreatic, gastric and hepatic enzymes, thereby resulting in the production of alpha-ketoacids attributing to the production of calories inside the human body. The evidence-based literature reveals the enhancement of protein synthesis and inconsistent patterns of protein degradation following the increase in protein uptake (Walsh Wright 1995:p.7). (b): The fasting state triggers the production of glucagon under the influence of protein kinase leading to glycogen catabolism and ATP production to antagonize the state of starvation. However, during prolonged starvation the intestinal, pancreatic and muscle proteins undergo gradual degradation for glucose production to meet the energy requirements of the body. (c): Vegetarians recommended adding complementary sources of proteins including nuts, grains and legumes in diet to ascertain the intake of essential amino acids required to accomplish the protein requirement of the body. (d): The intent of administering the complementary proteins follows the contention of supplying the essential amino acids through the foods that complement each other in context to accomplishing the requirement of all essential amino acids for the body tissues (Sizer et al, 2012:p. 208). The concept of mutual supplementation ensures the inclusion of protein rich supplements in food for generating complementary proteins, thereby avoiding the need to include single source of protein in one particular meal. 4. (a): The citric acid cycle attributes to the efficient metabolism of proteins, carbohydrates and lipids in human body resulting in the production of ATP for accomplishing the energy requirements of the body. (b): From the biochemical perspective, the molecules of GTP and ATP display different configuration; however, exhibit same energy content in their triphosphate groups as evidenced by the clinical literature. (c): The oxidation of NADH results in the production of 3 ATP molecules through the TCA cycle; however, FADH2 processing leads to the generation of 2 ATP molecules attributing to the consequent production of 12 ATP from the metabolism of single molecule of Acetyl CoA. References Goldstein, B Muller-Wieland, D 2007, Type 2 Diabetes: Principles and Practice, CRC, Florida Lodish, H, Berk, A Zipursky, SL 2000, Molecular Cell Biology (4th edn.), W. H. Freeman, NY Peet, A 2013, Marks' Basic Medical Biochemistry (4th edn.), Lippincott Williams Wilkins, Philadelphia Ranson, B 2007, Type 4 Diabetes: Elevated Insulin. Lower Blood Sugar. 24/7 Pain, BBG-Media, USA Satake, M 2003, Chemistry For Health Science (2nd edn.), Discovery, New Delhi Sizer, F, Whitney, E Piche L 2012, Nutrition: Concepts and Controversies (2nd edn.), Nelson Education, Toronto Springhouse 2008, Nursing Know-how: Evaluating signs symptoms, Lippincott Williams and Wilkins, USA Walsh Wright 1995, Nitrogen Metabolism and Excretion, CRC, USA