Pyruvate Metabolism 1 Identify different directions in which pyruvate metabolism may proceed Pyruvate is very versatile and can be interchanged with lactate alanine and glucose 2 or conversion of pyruvate to acetyl CoA A Recognize that reaction is irreversible How does this explain the general statement that glucose can t be synthesized from fat Fatty acid are turned into Acetyl CoA and never pyruvate Therefore they can never undergo gluconeogenesis and creat fat B Recognize this reaction as an example of oxidative decarboxylation of an alpha ketoacid Are Oxidation reaction in which a carboxylate group is removed forming CO2 3 Regulation of PDH TCA Cycle Krebs Cycle Citric Acid Cycle 1 Recognize and be able to give examples of this cycle s role as a common metabolic pathway e g where can its intermediaries originate What can they be diverted from the cycle and used for Carbohydrates Fatty acids and proteins can all be converted into Acetyl CoA and then go through the TCA cycle 2 Identify example of substrate level phosphorylation Formation of a reaction that results in ATP or CTP by the direct transfer of a phosphoryl group 3 Describe the role of OAA in regulating cycle activity OAA is necessary because it is used to form citrate Electron transport chain ETC 1 State the purpose and cellular location and list the components of the ETC The purpose is to capture energy in the form of ATP by coupling two processes of oxidation and phosphorylation The location of the ETC Is in the mitochondria 2 Discuss how ATP is synthesized via oxidative phosphorylation Transports protons across the inner mitochondrial membrane for phosphorylation of ADP to ATP 3 State why the maximum theoretical yield of ATP s for electrons introduced into the ETC via NADH H is 3 whereas for electrons introduced via FADH2 is 2 The FADH skips a complex allowing only 2 ATPs to be produced in comparison Fructose and Galactose Metabolism 1 Which enzyme is missing in individuals with galactosemia Missing GALT galactose1 PO4 uridyl transferase can cause liver Failure mental deterioration and cataracts 2 Metabolic Problems associated with fructose A Fructosemia or Essential Fructosuria Born with it Caused by lack of Fructokinase Excrete fructose in the urine Cannot phosphorylate fructose What is ingested will be secreted B Hereditary fructose intolerance Caused by lack of Aldolase Results in hypoglycemia Deficient in cleaving Fructose 1 PO4 to DHAP and Glyceraldehyde Add up of Fructose 1 PO4 Allosteric Regulation Tissue Variations 1 Liver a Discuss the role of the liver in glucose homeostasis Gluconeogenesis increase blood glucose Glucose from non carb substitutes to regulate blood glucose levels Glycogenolysis increase in blood glucose Breakdown of glycogen in liver to regulate blood glucose levels Glycogenesis decrease in blood glucose decrease blood glucose levels b Discuss hormonal regulation of glucose homeostasis Low blood Glucose Your body wants to increase the amount of glucose in the blood Glucose is then supplied to the blood in response to the following hormones a Glucagon promotes gluconeogenesis and glycogenolysis b Epinephrine Increase glycogenolysis c Glucocorticoids increase gluconeogenesis Cortisol increase which is a catabolic hormone Fasting blood glucose levels go down glucagon during mRNA level reacted by pyruvate carboxylase Epinephrine activate cAMP cascade Epinephrine not inducing pathway at mRNA levels High Blood Glucose Decrease in blood glucose in response to insulin Beta cells of pancreas a Increase glycogenolysis b increase glycolysis c increases HMP shunt Remember that NADH H is an important for Fatty acid synthesis Synthesizing more Proteins and Lipids 2 Muscle a Understand that muscles are self serving in terms of CHO metabolism because of a lack of glucose 6 phosphatase They lack glucose 6 phosphatase and that is important becase that is what is used to covert to glycogen b Note roles of insulin and GLUT 4 in glucose uptake by muscle Glucose Muscle Need GLUT 4 glucose transporter Usually in middle of cell not available for glucose cell Insulin regulates glucose uptake into these cells by recruiting membrane vesicles containing the GLUT 4 glucose transporters from the interior of cells to the cell surface where it allows glucose to enter cells by facultative diffusion Once in the cytoplasm the glucose is phosphorylated and thereby trapped inside cells The effect of insulin on GLUT 4 distribution is reversible Within an hour of insulin removal GLUT 4 is removed from the membrane and restored intracellular in vesicles ready to be re recruited to the surface by insulin Thus glucose uptake by muscle and fat cells is regulated by modulating the number of GLUT4 on the surface of the cells c Differentiate between muscle and liver CHO pathways major points and their significance d Explain the importance of glycogen for muscles Glycogen is the primary fuel for muscles Stored primarily in the cells of the liver and the muscles Short Response Question IRS4 activates GLUT 4 from interior of cell cell membrane for glucose to be uptaken 3 Brain a Know that the brain is most dependent on CHO metabolism Cannot use any other type of fuel than CHO metabolism b Note that it is necessary for CHO metabolism in the brain to operate aerobically to meet the high energy demands of this tissue c Predominate pathways Glycolysis TCA cycle Hexokinase low Km for glucose 4 Erythrocyte RBC a Explain why RBC s only operate anaerobically and how this makes them totally dependent on glucose Erythrocytes have no mitochondria and are restricted to anaerobic metabolism b Discuss the pathways which utilize glucose which are more prevalent and why they are necessary 5 Know that the kidney is a major contributor to gluconeogenesis in an adapted fast
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