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HNF461FS13 Exam 1 Study Guide Regulation of Energy Metabolism 1. AMDR – No exact numbers, need to know which accounts for the most and the rough ratio. - AMDR- acceptable macronutrient distribution range- Carbohydrates- 45-65% in adults and children - Lipids- 20-35% in adults and 30-40% in children- Protein- 10-35 % in adults and 5-20% in children2. What’s special about the macronutrient composition of milk compared to normal AMDR, human or animals? Why is it important? - Breast milk is high in fat - Lipids provide energy for infants - Less carbohydrates and protein in milk, but more fat.3. Understand what makes a pathway/reaction endothermic or exothermic. - Endothermic- absorb/ take in energy (gluconeogenesis) - Exothermic- releases energy (glycolysis); spontaneous 4. What is substrate level phosphorylation? - In substrate level phosphorylation high energy reactants (phosphoenolpyruvate, phosphocreatine, 1,3-diphosphoglycerate) with a phosphate group phosphorylate ADP to make ATP. 5. How is enzyme activity regulated? - Allosteric regulation- Phosphorylation/dephosphorylation - Control of enzyme gene expression 6. AMPK function, what actives AMPK? What pathways does AMPK targeting?- AMPK (AMP- activated protein kinase) is activated by high levels of AMP/ATP - Activation of AMPK stimulates processes that generate ATP, and inhibits those that consume ATP, but are not acutely required for survival - AMP promotes phosphorylation of AMPK and this activates the enzyme. Kinase is phosphorylated and activated- only case. - Leptin INHIBITS AMPK (you do not need energy since you are full- your adipocytes produced leptin)Glucose Metabolism. TCA and ETC 7. Fate of glucose in the cells. In other words, what is glucose used for? - Provide fuel for ATP synthesis - Glycogenesis (Glycogen synthesis- in liver and muscle) - Minor uses- synthesis of ribose, NADPH, glucose for glycoprotein and glycolipid synthesis - Lowest priority- substrate for fatty acid and TAG synthesis 8. The starting and end points of glycolysis, gluconeogenesis, glycogenesis etc etc. Fig 3-12.- Glycolysis: start- glucose end- 2 pyruvate- Gluconeogenesis: start- pyruvate end- glucose- Glycogenesis: start- glucose end- glycogen - Glycogenolysis: start- glycogen end- glucose 9. The regulated/irreversible steps in glycolysis. How is each step regulated by allosteric molecules, phosphorylation/dephosphorylation, and other mechanisms, for example, the translocation of GK. What role do hormones play in those regulations? Pay special attention to glucagon. - Hexokinases (inhibited by glucose-6-phosphate product inhibition). Has a higher Km lower affinity than glucokinase. - Glucokinase (in liver) is inhibited by fructose-6-phosphate and directly stimulated by glucose glucose induces translocation - Phosphofructokinase. Inhibited by ATP and citrate. Activated by AMP and high levels of fructose 2,6 bisphosphate. High levels of fructose-2,6-bisphosphate means that there is low levels of fructose 1,6-bisphosphate, so reaction goes in the forward direction (fructose-6-phosphate fructose-1,6-bisphosphate). Insulin also activated PFK2. Glucagon inhibits this enzyme.- Pyruvate kinase- When glucagon level is high, pyruvate kinase is phosphorylated and inactivated. Thus, you cannot make pyruvate from phosphoenolpyruvate. 10. What does glycolysis consume and what does it produce? - Glycolysis consumes 2 ATP. - It produces 2 net ATP. - It produces 2 NADH. 11. How is glycolysis connected to the TCA cycle? - Glycolysis forms pyruvate which is then converted into acetyl-coA through the pyruvate dehydrogenase complex - Acetyl-coA enters the TCA cycle by reacting with oxaloacetate citrate- The pyruvate dehydrogenase complex forms an NADH (and acetyl-CoA) in order to regenerate the FADH2 used.12. How does it connect to ETC? - The TCA cycle oxidizes substrates by removal of hydrogens to an electron acceptor to produce NADH and FADH2 - The TCA cycle also produces carbon dioxide- The NADH and FADH2 from the TCA cycle travel to the ETC in order to generate ATP with the proton-motive force.13. What does TCA cycle consume and produce? - The TCA cycle consumes 6 NAD, 2 FAD, and 2 GDP- The TCA cycle produces 6 NADH, 2 FADH2, and 2 GTP, and 2 CO214. What does a cell do with the NADH made by glycolysis? - The NADH made from glycolysis goes through the malate-aspartate shuttle (oxaloacetate+ NADH malate mitochondria malate- NADH oxaloacetate) or the glycerol-3-phosphate (DHAP+ NADH glycerol 3-phosphate donation of H to FAD in mitochondrial matrix) channel to get to the mitochondrial matrix.15. Understand the concept of oxidation/reduction. The flow of electrons. - Oxidation- take away electrons- Reduction- addying electrons 16. How ETC works to make ATP? - The ETC uses the proton-motive force to make ATP.17. What’s UCP1 for? Why is it important? - Uncoupler 1. - There is a high number in the mitrochondria. - Used in brown adipose tissue to generate heat for temperature regulationGI. Insulin Glucagon Action. Glycogenolysis. 18. Know where the source of glucose is at different hours after fasting. - First 4 hours glucose- After 4 hoursglycogen/gluconeogenesis - After 16 hours gluconeogenesis…. 19. Know the concept of GI. What is it useful for? What might influence it? - Glycemic index estimates how much gram of carbohydrate in food raises a persons blood glucose level, relative to the consumption of pure glucose- Area under curve of food/ are under curve of pure glucose x 100%= GI- Determinants of glycemic index of foods: the rate of glucose taken up by the food, and the rate of glucose transport into tissue 20. What organs and tissues are important for blood [glucose] regulation? How doeseach tissue or organ contribute individually? What hormones are involved? What’s the target organ for each hormone? Focusing on glucagon, what specific enzymes in what pathways are regulated by glucagon and how does that contribute to blood glucose control? - Liver- glycogenolysis and gluconeogenesis - Pancreas- insulin and glucagon - Insulin- targets muscle cells - Glucagon- targets liver cells (for gluconeoegenesis) - Glucagon activates protein kinases which activate glycogenolysis 21. What is glycogen? Why is it important? How glycogenolysis is controlled by hormones? What enzymes are involved and how each enzyme is regulated? - Glycogen is a polymer of glucose - It is the storage form of glucose- Glucagon

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MSU HNF 461 - Exam 1 Study Guide

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