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CU-Boulder IPHY 4440 - Exam 2 Study Guide
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IPHY 4440 1st EditionExam# 2 Study Guide Lectures: 7-13Lecture 7 (Feb 3) Introduction to membrane receptors Describe the receptors on the cell surface. What are some important features and give examplesof some hormones that bind to these receptors on the surface. Then describe some lipid soluble molecule features and some examples. Receptors on cell surface:- Water-soluble, cannot readily pass through the membrane, receptors embedded on the membrane- Examples: biogenic amines, peptides, proteins Lipid soluble molecules:- Can either bind inside or outside the cell- Depending on where its bound (on what tissue), can either bind intracellularly or on membrane receptors - Example: thyroid and steroid hormones Name the three domains where these membrane receptors can be? 1) Ligand-binding domain= extracellular (always bind outside the cell)2) Transmembrane domain= crosses membrane and contacts cytosol 3) Intracellular domains: inside the cytoplasm Why are GPCR (G protein coupled receptors) important?- Most abundant membrane receptor in our bodies- Not an enzyme, ion channel, or transcription factor! Relies on generation of second messengers to activate cellLecture 8(February 5th) How does occupied receptor bring about change in a target cell?- Can either form homodimers or heterodimers- If cannot open/close ion channels, function as an enzyme, or function as a transcription factor then must activate a second messenger.. GCPRs do this and can now increase enzyme or ion channels or act on transcription factors Map out the typical second messenger pathway.- Bioregulator (1st messenger)  occupied receptor  activate effector protein = signal generating protein (different than R)  second messenger  effect- The signal-generating protein acts directly on some sort of substrateList the cAMP pathway in the liver starting with epinephrine binding to its substrate.- E binds to B-adrenergic receptor (GPCR)  activates enzyme system  AC (adenylcyclase)  Converts ATP  to cAMP  activate PKA (protein kinase A)  phosphorylase kinase A phosphorylase B (inactive state)  phosphorylase A (active) glycogen  glucose-phosphate  1) metabolism via glycolysis/krebs cycles or 2) enter blood as free glucose Describe the amplification system and the importance of the steps.1st messenger  2nd messenger  protein kinase  (+) enzyme  tons of effects- It is a cascade of events and second messengers that have the ability to amplify their biological effects- Amplify effects with every step – very flexible - This system is why hormones can exist at such low levels but create so many biological effects - Second messengers can produce different effects depending on the tissue and the enzymes availableWhat effects does the second messenger cAMP have when it binds to epinephrine on the adipose tissue and on the cardiac muscle?- - cAMP in the adipose tissue activates PKA that is either a hormone-dependent lipase or induce lipolysis (breakdown of fats) - cAMP in cardiac muscle activates PKA which opens calcium channel (keeps them more open and for longer) to create stronger and more sustained contractionsThere are three ways to shut this amplification system down. What are they and give a description of each. - Inactivation of ligand= degrading enzyme in cell membrane and in extracellular fluids, bio-regulators do not persist for a very long time, enzymes have more specific purposes that make sure they don’t stay around for too long - Reuptake of ligand by secreting cell: works for neuromodulators, neurotransmitters,paracrine/autocrine but not hormones..why?Because hormones end up in the blood,as soon as secreted it is quickly transported and Neurocrines are released into synapse so easy to take back up - Internalization of occupied receptors: Clathrin-coated pits: patch of membrane, induce endocytosis (endosomes) and fuse with lysosomes called endolysosomes (break down stuff in vesicles), another way to shut down the system, can also degrade or recycle, goal of internalized receptors are to destroy Review: name the three membrane receptor types and what they are specialized to do. 1) G-protein coupled receptors (bind GTP to GDP)- All G-proteins have 3 subunits: alpha, beta, gamma2) Receptors with inherent enzyme activity - 3) Receptors that are ion channels (mostly neurotransmitter receptors): Inactive state (gamma-beta-alpha-GDP)- Active state gamma-beta dissociates from alpha-GTPLecture 9 (February 10th) What does “cross-talk” mean in Endocrinology? One messenger can affect another messenger via common intracellular pathways (Just know that they do occur along these pathways)What are nuclear receptor families and give some examples:- Over 300 members identified, they are all transcription factors, most ligands are unknown: orphan receptors - Transcription factors: orphans, no known ligand. - Ligand activated: has known ligand = ligand activated transcription factors (LATFs)- Examples:- Orphans: Aryl hydrocarbon receptor (AhR) or SF-1 receptor- LATFs: Steroid receptors, Thyroid receptors, Retinoic acid receptor, 1, 25 dihydroxy Vitamin D3 receptorThere are 4 classes of steroid receptors. List the name of each class and go in to detail about each one.- Estrogen receptors (ER): Era (alpha), ERb (beta) (different affinities for various ligands) E1, E2, E3 are promiscuous SERMs Phthalates, BPA, Nonylphenol, Pesticides, Phytoestrogens, etc. - Androgen receptors (AR): two isoforms, A & B. Greatest affinity DHT > T > AND > DHEA- Corticoid receptors (GR & MR): glucocorticoid receptor (GR) binds only coritcosterone or cortisol -Progesterone receptors (PR): mineralocorticoid receptor (MR) B, F > aldosteronetwo forms: PR-A & PR-B, progesterone is most common progestogen ligand MR binds to both glucocorticoids as well as mineralocorticoids with greater affinity to B,F then Aldo What do type 1 GR and type 2 GR stand for?- Type 1 GR: GR-1 binds B, F > aldosterone = MR- Type 2 GR: GR-2 binds B & F only = GR*So glucocorticoids can activate both GR and MR*What are the thyroid receptors? - TRa, TRB1, TRB2 - Retinoic acid receptor: RAR & RXR (retinoic X receptor, orphan)- Both can dimerizeWhat is unique about the Aryl hydrocarbon receptor (AhR)?- It is an orphan because no naturally occurring ligand that we produce to bind AhR so binds to things external, binds to environmental contaminants (PCBs, dioxins)/external contaminants, this particular receptor has evolved


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CU-Boulder IPHY 4440 - Exam 2 Study Guide

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