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 children 2 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 CO2 14 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 regulation GI 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 does each 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 activates glycogenolysis need E glucagon activates protein kinases protein kinase A which activate glycogenolysis activation of glycogen phosphorylase 22 In the broad scheme of things what happens to hormone levels in the blood during fasting fed states and during exercising and fight or flight response What pathways the ones we learned are active