BMB 462 Lecture 16 Outline of Last Lecture I Ammonia incorporation into Carbon Compounds II Amino Group Transfers III Amino Acid Anabolism IV Important biomolecules derived from Amino acids V Hormonal Signaling VI Hormone Classification Outline of Current Lecture I Continuation of Hormone Classification II Hormone Signaling Cascades III Specialized Metabolic function of Tissues IV Major Metabolic Pathways in the Liver V Secretion and Effects of Insulin VI Effects of Glucagon VII Stored Metabolic Fuels VIII Effects of Epinephrine IX Effects of Cortisol Current Lecture Concepts to remembers from previous courses lectures I Continuation of Hormone Classification a Release point Target tissue i Endocrine insulin glucagon cortisol and epinephrine are all endocrine hormones 1 Endocrine paracrine and autocrine differ based on their release point vs the target tissue 2 Endocrine hormones are released from somewhere and then have to travel through bloodstream to targets that are farther away These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute a i e insulin and glucagon are produced in pancreas and then travel through the blood to the liver muscle tissues adipose tissues etc ii Paracrine works locally doesn t move through blood i e eicosanoids like prostaglandins and leukotrienes iii Autocrine works on same cell that creates them II Hormone Signaling Cascades a Cortisol signals come from outside for cortisol it s stress i Causes the central nervous system to cause the hypothalamus to release hormones called releasing factors 1 The releasing factors activate the anterior pituitary then corticotrophin goes to adrenal cortex and causes cortisol to be released and act on many things to help deal with long term stress a This illustrates amplification Initially release ng quantities of initial signals which release ug quantities which release mg quantities b Also an example of feedback inhibition The more cortisol is present it inhibits previous target Presence of that target inhibits the one before it b Epinephrine Epinephrine is essentially the opposite of cortisol It is the fight or flight hormone instead of spending time making and releasing various hormones when the signal is sensed the body gives an immediate response c Insulin and Glucagon insulin and glucagon don t go through the central nervous system Blood glucose levels and the pancreas control release of insulin glucagon to target tissues III Specialized Metabolic function of Tissues a The liver s job is to store and release energy Everything that comes in nutrients fats carbs proteins goes to liver to determine what happens to them storage breakdown etc i Regulated by the pancreas the pancreas controls whether the liver breaks down or makes molecules by releasing insulin and glucagon b The brain requires constant glucose for blood If there is insufficient glucose it can substitute in ketone bodies i So the liver s main job is monitoring blood glucose levels and controlling them to make sure there s enough energy for the brain to keep functioning ii The brain stores NO energy neither as fat or glycogen iii Fatty acids can t be imported into brain in a way that can be used as energy c Adipose tissue is the main storage for lipids d Muscles store glycogen for their own use e The liver stores glycogen to replenish blood sugar levels IV Major Metabolic Pathways in the Liver a Pathway example Glucose metabolism i GLUT2 moves glucose into and out of liver depending on concentration ii Glucokinase phosphorylates the glucose to make glucose 6 phosphate iii Then it gets dephosphorylated and sent back out through GLUT2 into the blood stream iv Glucose can then be stored in the liver as glycogen for energy use later v Metabolism of glucose also prevents oxidative damage by reducing the molecules via NADPH vi Produces energy by putting carbons through the TCA cycle b Look at Amino Acid Metabolism and Fatty Acid Metabolism on your own c Control of the Liver by the Pancreas i Both glucagon and insulin are peptide hormones Both start out longer and then undergo proteolytic cleavage ii It s not like you re producing glucagon or insulin always some of both being produced at all times It s not like regulation completely stops one or the other 1 Instead the levels of each hormone compete and the more prevalent hormone triggers the desired reaction Integrating the levels of glucagon and insulin in the cells and the ratio determines which target enzymes are being phosphorylated and how much which then determines what s happening iii General rule 1 Effect on target enzyme i e glycogen synthase a target enzyme that is controlling metabolism 2 Insulin causes dephosphorylation of target enzyme to regulate it Glucagon and epinephrine phosphorylate the enzyme These are the effects on the final target of signal cascade iv How does pancreas decide how much insulin is secreted based on glucose levels Involved in insulin release 1 Order of action a Glucose is taken into pancreas through GLUT2 transporter same one used in the liver As it comes in it goes through glycolysis causes increase in ATP ATP acts as ligand for ligand gated K channel blocks the channel closing of K channel the sodium potassium pump keeps k flowing into cell membrane depolarization Opening of Ca channel b Membrane is positive outside so when you stop moving K positive ions outside the membrane is depolarized because more positive inside so less of a charge difference across the membrane c Insulin causes increase in GLUT4 receptors in muscles and adipose tissue so taking up glucose out of blood stream and liver starts metabolism of glucose This means blood sugar levels and levels in pancreas go down which decreases the ATP ADP ratios which will reopen the K channel the membrane will re polarize and the pancreas will stop releasing insulin 2 Effect of insulin release is to reduce blood glucose levels which will cause feedback to reduce insulin release 3 Increase in GLUT4 receptors in muscles and blood stream so glucose levels go down which reduces ATP and allows the K channel to reopen 4 Pancreas releases insulin so that blood sugar goes down When it s low enough the system shuts itself off V Effects of Insulin a Insulin results in dephosphorylation of target enzymes b When glycogen synthase is dephosphorylated it s more active When Glycogen phosphorylase is dephosphorylated it s less active c
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