BMB 462 Lecture 16 Outline of Last Lecture I. Ammonia incorporation into Carbon CompoundsII. Amino Group TransfersIII. Amino Acid AnabolismIV. Important biomolecules derived from Amino acidsV. Hormonal SignalingVI. Hormone Classification Outline of Current Lecture I. Continuation of Hormone ClassificationII. Hormone Signaling CascadesIII. Specialized Metabolic function of TissuesIV. Major Metabolic Pathways in the LiverV. Secretion and Effects of InsulinVI. Effects of GlucagonVII. Stored Metabolic FuelsVIII. Effects of EpinephrineIX. Effects of CortisolCurrent LectureConcepts to remembers from previous courses/lectures:-I. Continuation of Hormone Classificationa. Release point/Target tissuei. Endocrine - insulin, glucagon, cortisol and epinephrine are all endocrine hormones1. Endocrine, paracrine and autocrine differ based on their release point vs. the target tissue.2. Endocrine hormones are released from somewhere and then haveto 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 themII. Hormone Signaling Cascadesa. 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 releasemg 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/glucagonto target tissues.III. Specialized Metabolic function of Tissuesa. 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 energyc. 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 levelsIV. Major Metabolic Pathways in the Livera. Pathway example: Glucose metabolismi. GLUT2 moves glucose into and out of liver, depending on concentrationii. Glucokinase phosphorylates the glucose to make glucose 6-phosphate.iii. Then it gets dephosphorylated and sent back out through GLUT2 into the blood streamiv. Glucose can then be stored in the liver as glycogen for energy use laterv. Metabolism of glucose also prevents oxidative damage by reducing the molecules via NADPHvi. Produces energy by putting carbons through the TCA cycle b. Look at Amino Acid Metabolism and Fatty Acid Metabolism on your ownc. Control of the Liver by the Pancreasi. Both glucagon and insulin are peptide hormones. Both start out longer and then undergo proteolytic cleavageii. 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 metabolism2. 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 glucoselevels? Involved in insulin release1. Order of action:a. Glucose is taken into pancreas through GLUT2 transporter (same one used in the liver). As it comes in, it goes throughglycolysis (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+ channelb. Membrane is positive outside so when you stop moving K (positive ions) outside, the membrane is depolarizedbecause more positive inside, so less of a charge differenceacross 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 Insulina. Insulin results in dephosphorylation of target
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