HUN 3224 Exam 2 1 TCA cycle a Know various names for this cycle Krebs cycle Citric acid cycle b Recognize and be able to give examples of this cycles role as a common metabolic pathway Proteins Carbohydrates Lipids Amino Acids Pyruvate Fatty Acids Acetyl CoA TCA cycle i Acetyl CoA is the linkage to all of the pathways ii Synthesizing molecules are used for transamination of Amino c Know reactions enzymes energetics etc Acids i Energetics ATP Isocitrate ketoglutarate CO2 NADH H 3 ATP 1 2 ketoglutarate Succinyl CoA CO2 NADH H 2 3 Succinyl CoA GDP Succinate GTP 1 ATP 4 Succinate Fumarate FADH2 2 ATP 5 Malate OAA NADH H 3 ATP 6 TOTAL 12 ATP molecule of Acetyl CoA ii Rate Limiting enzymes 1 Citrate synthase 2 3 ketoglutarate dehydrogenase Isocitrate dehydrogenase iii Reactions 1 8 steps starts with citrate and ends with OAA 2 Formed 1 GTP 3 NADH H 1 FADH2 2 CO2 d Example of Substrate level phosphorylation i Succinyl CoA GDP succinate GTP e Role of OAA in regulating cycle activity i Oxaloacetate and acetyl CoA form citrate using the enzyme citrate ii synthase initiating the TCA cycle If the amounts of OAA from9p pyruvate is limited such as fasting situations or carb restriction then citrate synthase is inhibited and TCA doesn t occur iii Ex uncontrolled diabetes f Role of NADH and ATP in controlling citric acid cycle activities i NADH H 1 If increases this inhibits dehydrogenases a Dehydrogenase removes hydrogen s from substrates to add to NAD ii ATP 1 2 Electron Transport Chain Inhibits citrate synthase and isocitrate dehydrogenase causing the TCA cycle to slow down a State the purpose and cellular location and list the components i Cell location mitochondria if cell does not have this TCA cycle cannot occur Ex RBC ii Purpose to capture energy in the form of ATP by coupling the two processes of oxidative phosphorylation iii Components 1 Proton pumps 2 Electron Transporters a Complexes which remove electrons from coenzymes located in the inner mitochondrial space or pump protons into the space i Complex 1 NADH dehydrogenase complex ii Complex 3 Cytochrome B C complex iii Complex 4 Cytochrome oxidase complex a Transport electrons between complexes in the electron transport chain i Ubiquinone complex 2 or coenzyme q 1 Transports electrons between complex 1 and 3 helping them get to the complexes ii Cytochrome C transports electrons between complex 3 and 4 contain iron 3 Complex 2 cannot pump protons b Discuss how ATP is synthesized via oxidative phosphorylation i ATP is used to pump protons into inner membrane space creating a gradient Once the gradient is diffused protons flow back to matrix this can be used to make ATP IF protons diffuse back through ATP synthase c State why maximum theoretical yield of ATPs for electrons introduced into the ETC via NADH H is 3 whereas for electrons introduced via FADH2 is 2 i NADH H enters through complex 1 while FADH2 enters through complex 3 causing one less H to be released ii NADH is formed in the mitochondria 1 The enzyme transferring NADH is NADH dehydrogenase in complex 1 Once it is transferred coenzyme q accepts H and transfers it to complex 3 The structure accepting the hydrogens in complex 3 is called cytochrome c which then takes the hydrogen to complex 4 2 No protons are pumped in complex 2 3 For every NADH formed 4 hydrogen s are released into the inner membrane space happening in complex 1 and 3 In complex 4 it only pumps out 2 hydrogen s because 2 are used to reduce oxygen to water 3 Fructose and Galactose Metabolism a Why are fructose and galactose metabolized primarily in the liver i Liver is the major sight because hexokinase in muscle has a higher affinity lower Km for glucose vs fructose and galactose b Discuss how ingestion of large amounts of fructose may have detrimental metabolic consequences STEPS i Fructose is converted to Fructose 1 Phosphate using Fructokinase ii During this step ATP is made into ADP Fructose 1 Phosphate ADP is catalyzed into DHAP glyceraldehyde using Aldolase B iii Glyceraldehyde can be catalyzed into glyceraldehyde 3 phosphate using trio kinase and making another ADP which then can go to glycolysis along with DHAP DHAP and glyceraldehyde can catalyze to fructose 1 6 bis phosphate which would favor gluconeogenesis using aldolase A Since both can enter glycolysis or gluconeogenesis after the enzyme PFK 1 it means that there is no rate controlling enzyme to regulate the amount being metabolized more triacylglycerol formation iv Excess fructose can lead to excess fatness increased risk of heart disease 1 Fructosemia excrete fructose in the urine caused by 2 Fructose intolerance results in hypoglycemia caused by fructokinase lack of aldolase c Understand how fructose and galactose enter the metabolic pathways i Fructose triose phosphate pyruvate acetyl CoA FA TAG ii Galactose Metabolism makes glucose and energy 1 Galactose Galactose 1 phosphate by galactokinase making ADP 2 Galactose 1 phosphate UDP galactose by galactose 1 phosphate uridyl transferase UDP glucose glucose 1 phosphate 3 UDP galactose UDP glucose by UDP galactose 4 4 UDP glucose glycogen by glycogen synthase 5 Glycogen Glucose 1 phosphate by glycogen epimerase phosphorylase 6 Glucose 1 phosphate glucose 6 phosphate 7 Glucose 6 phosphate glucose by glucose 6 phosphatase UDP glucose can feedback to supply the substrate in galactose metabolism d Which enzyme is missing in individuals with galactosemia i Missing galactose 1 phosphate uridyl transferase 1 Can cause liver failure mental retardation and cataracts 2 Unable to go from galactose 1 phosphate to UDP galactose 4 Tissue Variations a Liver i Discuss the role of the liver in glucose homeostasis 1 Gluconeogenesis high blood glucose 2 Glycogenolysis high blood glucose 3 Glycogenesis low blood glucose a During low blood glucose starvation your body wants to increase the blood glucose using certain hormones ii Discuss hormonal regulation of glucose homeostasis 1 Glucose is supplied to the blood in response to the following hormones glycogenoylysis a Glucagon promotes gluconeogenesis and b Epinephrine glycogenolysis c Glucocorticoids gluconeogenesis 2 During high blood glucose fed state a You want to lower the blood glucose level i In response to insulin 1 2 3 Increases glycogenesis Increases glycolysis Increase HMP shunt b Muscle glycolysis and glycogenolysis glycogenesis i Understand that muscles are self serving in terms of CHO metabolism because of a lack of glucose 6 phosphatase ii Note roles
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