Transcript for:
Comprehensive Overview of Digestive System

1/27/25 Alimentary canal begins in the mouth Digestive process: * Ingestion * Physical digestion mastication (chewing) * Chemical digestion: enzymes * Propulsion: swallowing Mouth: * Teeth - used in mastication * Tongue - synthesizes and secretes enzymes; will also position food into bolus * Salivary glands - synthesizes and secretes saliva (ions, glycoproteins, enzymes, waste products, water, lysosomes) helps maintain pH of 7 in the mouth and helps lubricate the bolus Enzymes produced in mouth: 1. Salivary amylase: breakdown of starch and glycogen 1. Synthesized and secreted by salivary glands 2. Active in mouth, pharynx, and esophagus 3. Inactive in the stomach 2. Lingual lipase: breakdown of lipids 1. Synthesized and secreted from tongue 2. Inactive in mouth, pharynx, and esophagus 3. Active in the stomach What type of digestion occurs in the mouth? * Chemical and mechanical! * Chemical: salivary amylase * Mechanical: mastication Pharynx and esophagus * Pharynx: area where both air and food travels * Esophagus: moves only food * Upper esophageal sphincter: smooth muscls that controls movement of bolus into esophagus * Upper ⅔ of esophagus composed of smooth muscle (involuntary) and skeletal muscle (voluntary) * Lower ⅓ of esophagus composed of only smooth muscle (involuntary) * Lower esophageal sphincter: prevent stomach juices (highly acidic) from entering esophagus After the esophagus, what is the next part of the alimentary canal? Stomach! Stomach: Regions: * Fundus: top part * Body: middle part * Pylorus: last part Other structures: * Rugae: folds that allows stomach to expand * Pyloric sphincter: controls the movement of chyme into small intestine * Surface mucus cells: cover stomach, synthesize and secrets alkaline mucus to protect surface of the stomach * Gastric pits: connects stomach to gastric glands Cells in the gastric pits: * Parietal cells: s/s HCl - kills microorganisms; also s/s intrinsic factor (molecule needed for B12 absorption) * Mucus neck cells: s/s mucus - function is unknown! * Chief cells: s/s pepsinogen (inactive form of pepsin (protease - digest proteins)) * Enteroendocrine cells: s/s hormone (ex: G cells s/s gastrin (hunger…)) What digestive processes occur in the stomach? Propulsion: peristalsis and gastric emptying Mechanical digestion: gastric mixing Chemical digestion: pepsin (proteins), lingual lipase (lipids), gastric lipase NO absorption happens in the stomach! Match cell with what it produces: Surface mucus cells: Alkaline mucus Parietal cells: Hydrochloric acid (HCl) Chief cells: Pepsinogen Enteroendocrine cells: Gastrin Small intestine: What digestive processes occur in the small intestine? * Propulsion: peristalsis * Chemical digestion: enzymes * Mechanical digestion: segmentation * Absoption of nutrients!! Duodenum Jejunum Ileum Structures and cells: 1. Circular folds: increase surface area for absorption 2. Villi: increase SA for absorption 3. Microvilli: increase SA for absorption; also contain brush border enzymes (chemical d) 4. Goblet cells: s/s mucus (provides protection and lubrication) 5. Crypts of Lieberkuhn: s/s intestinal juices (lubricate SI and buffers HCl from stomach) The molecules used in the small intestine to digest lipids are: a. Bile b. Pancreatic lipase e. Co-lipase Large Intestine: Ileocecal sphincter: separates SI from LI Internal anal sphincter: smooth muscle (involuntary) External anal sphincter: skeletal muscle (voluntary) What is the main function of the large intestines? * Finish absorption * Absorb H2O - form and defecate feces Digestive processes within the large intestines? * Some absorption * Propulsion: mass movement; peristalsis * Mechanical digestion: haustral contractions; mass movement * Defecation * NO chemical digestion in LI ACCESSORY ORGANS Liver/gallbladder: 1. Synthesizes bile 2. Removes old RBCs 3. Processes nutrients after a meal 4. Processes nutrients between meals 5. S/s hormones 6. S/s plasma proteins 7. Help eliminate wastes 8. Store essential vitamins (vitamin A) Bile salts: * Synthesized in liver from cholesterol * Sectredted in bile to duodenum * Amphipathic molecule (polar and nonpolar) * Emulsify fat * Turns big fat glob into lots of smaller fat droplets that are surrounded by water * Increases SA of the fat (helps with digestion) * Nonpolar parts face lipids; polar parts face water * DO NOT digest fats; only emulsify What part of the bile molecule should face water? Polar Pancreas - s/s pancreatic juice (Exocrine factor) * Contains zymogens: Inactive proteases (activated in the small intestine * Bicarbonate buffer juice: base that neutralizes HCl from the stomach w/ small intestine * Co-lipase: molecule that helps load lipase onto lipids * Enzymes: pancreatic lipase; pancreatic amylase (starch/glycogen) Zymogens: inactive storage form of proteases produced via exocrine acinar cells of the pancreas * Trypsinogen * Chymotrypsinogen * Procarboxypeptidase Pathway: 1. Acinar cells 2. Pancreatic duct 3. Ampulla of vader (pancreatic duct joins w hepatic/cystic duct) 4. Sphincter of oddi (controls how much juice gets into small intestine) 5. Duodenum Pancreatic Acinar cells: s/s zymogens -hydrophilic -exocytosed -can’t pass through membrane -proteins are hydrophilic Make zymogens via protein synthesis * Dna transcripted into mRNA → translated by ribosomes on the rough endoplasmic reticulum → peptides will undergo modification within rough ER → travel to golgi apparatus→ packaged into zymogen granules (secretory vesicles) → exocytosed into pancreatic duct (out of acinar cells) → ampulla of vader → through open sphincter of Oddi → duodenum of SI → in SI - zymogens are actived by brush border enzymes (BBE) Which of the following is NOT matched correctly with the corresponding term? Parietal cells: Pepsinogen Crypt of Lieberkuhn: Intestinal juice Lactose: Disaccharide Microvilli: Brush border enzymes Carbohydrate digestion and absorption Generic term for the enzymes that breakdown polysaccharides: amylase Where are these enzymes synthesized and secreted? Salivary glands and pancreas Starch/glycogen → maltose + limit (alpha) dextrins Maltose (bbe) → 2 glucose Dextrinase (bbe) → glucose Sodium/ potassium pump role in absorption: 3 Na out → ICF [low Na] Establish a Na gradient in epithelial cells to allow cotransport of nutrients against gradient into cells Absorption of Carbs: (only absorb monosaccharides) Glucose apical: cotransport with Na (form of active transport) Basolateral: facilitated diffusion (glucose from lumen of GI tract into blood) (passive but needs TM bc its hydrophilic) Galactose Apical: same as glucose Basolateral: same as glucose Fructose apical: facilitated diffusion Basolateral: facilitated diffusion Proteins: * Typical diet: 125 g/day (only require 40-50g) * Proteins to be absorbed / digested * Consumed * Secreted into lumen of intestinal tract (enzymes) * Sloughed off with cells lining intestinal tract (enterocytes) * Generic term for enzymes that break down proteins = proteases * Proteins: * Amino acids (AA) * Dipeptides (AA-AA) * Tripeptides (AA-AA-AA) What types of enzymes digest proteins? Proteases Types of proteases: * Endopeptidases * Split polypeptides at interior peptide bonds * Cleave inside bonds * Product = small peptide fragments (di/tripeptides) * Exopeptidases * Cleave off amino acis from one end of polypeptide * Product = amino acids * Cleave outside bonds (individual) Protein digestion in the stomach (start): Chief cells - s/s pepsinogen Parietal cells - HCl & intrinsic factors Ingested protein → pepsin→ dipeptides and tripeptides (ENDOpeptidase) Protein digestion in the small intestine: Water released from pancreas (zymogens (inactive)) → activated by enzymes → Trysinogen activated by BBE enterochymase → trypsin (activated) → digest proteins into di/tri peptides → trypsin also converts chymotrysiogen into chymotrypsin → di/tri peptides → trypsin converts PCX into carboxipeptidase → digest proteins into amino acids Trypsin = endopeptidase Chymotrypsin = endopeptidase Pepsin = endopeptidase Carboxypeptidase (ONLY) = exopeptidase Absorption of Amino Acids: Need Na/K pump (establish sodium gradient) (pump out K, pump in Na) * We want low Na * Allow amino acids to go against gradient (co-transport) Apical: co-transport w/ Na (high to low) Basolateral: facilitated diffusion Convert di/tri peptides into amino acids with brush border enzymes (aminopeptidase/ dipeptidase) Carrier protein Absorption of di/tri peptides: Apical - co transport w Hydrogen ions within epithelial cells of GI Di/tri peptides → individual AA (cross basolateral membrane via facilitated diffusion) What happens to di/tri peptides in the small intestines? Absorbed across the apical membrane with co-transport with hydrogen ions Broken down by brush border enzymes into individual amino acids Absorbed across the basolateral membrane with co-transport with hydrogen ions A and B are correct B and C are correct 2/3/25 Lipids - 25-160g lipids * 90% triglycerides * Not water soluble * Do not mix * Enzymes of digestion = lipases * Secreted from * Lipases can only act on molecules near edge of fat droplet * Bile salts increase SA of droplets by breaking large droplet into several small droplets = emulsification * Co-lipase is needed to help load lipase onto lipid Lingual lipase - s/s from tongue, activated in the stomach Gastric lipase - s/s from stomach Pancreatic lipase & colipase - s/s from pancreas Bile - made in liver; stored/concentrated in gallbladder Lipoprotein lipase (blood) - s/s from liver Action of bile salts and colipase Bile salts - emulsify lipids → increases SA of lipids to allow water soluble lipase efficient digestion Co-lipase - move bile salts out of the way to load lipase onto the lipid Absorption of Lipids: 1. Micelles release lipophilic molecules 2. Lipophilic molecules cross apical membrane via simple diffusion 3. Smooth ER - reassemble molecules into a triglyceride 4. Triglycerides travel to golgi apparatus 5. In GA, add proteins and other lipids to triglycerides → molecule is now hydrophilic 6. Transformed into chylomicron (hydrophilic!) 1. Crosses basolateral membrane via exocytosis 2. Too large to be absorbed via capillaries 3. Bypass capillaries 7. Enter lymphatic system via lacteals 1. To blood (lipoprotein lipase (blood) 2. Digests chylomicrons into glycerols and fatty acids 3. Fatty acids and glycerols enter cells via simple diffusion Important to not have globs of fat in bloodstream! → fat embolisms Chylomicrons = way for fat/lipids to be absorbed in bloodstream What happens to bile salts? Enterohepatic circulation * Absorb the bile in ileum → recycled by liver How do fat soluble vitamins (lipophilic) get absorbed across the apical membrane of epithelial cells of the GI tract? Simple diffusion LIPOPHILIC = simple diffusion Fat soluble vitamins - A, D, E, and K * Absorbed w lipids * Dissolve with micelles, simple diffusion Water soluble vitamins - B and C * Carrier proteins B12 - intrinsic factor (parietal cells) Calcium: absorbed in duodenum/jejunum * Binds to BBE = calcium binding protein * Into epithelial cell Water: water in GI tract * 7 liters from GI secretions * 2 liters * Passive * Follows absorption of solutes by osmosis * Where does most water absorption occur in GI tract? Large intestine Sue has a genetic mutation that decreases the amount of enterokinase proteins on the brush border of her small intestines. What will be the result of her disorder? Less carbohydrate digestion Less lipid digestion Less protein digestion More carbohydrate digestion READING 3 Presence of oxygen AKA: aerobic respiration/complete oxidation 1. Glycolysis 2. Pyruvate oxidation (linking step; transition stage) 3. Krebs cycle (TCA; citric acid cycle) 4. Oxidative phosphorylation 1. Electron transport chain 2. Chemiosmotic coupling Absence of oxygen AKA: anaerobic respiration/ incomplete oxidation 1. Glycolysis 2. Fermentation Carbohydrate Metabolism NEED to know * What goes into each pathway * What comes out * Location First Pathway: Glycolysis: Location: Occurs within cytoplasm In: 1 glucose, 2 ATP, 2 NAD+, 4 ADP Out: 2 ADP, 2 NADH, 4 ATP, 2 pyruvates Costs 2 ATP Make 4 ATP NET: 2 ATP ONLY PATHWAY THAT REQUIRES ATP 2/5/25 Second pathway: linking step (Pyruvate Oxidation) Location: mitochondrial matrix In: 2 pyruvates 2 NAD+ 2 CoA Out: 2 CO2 2 NADH 2 Acetyl CoA What are the products of the linking step per glucose molecule? 2 Acetyl CoA, 2 NADH, 2 CO2 Third Pathway: Krebs Cycle, TCA cycle/citric acid cycle Location: in mitochondria matrix In: 2 Acetyl coA 6 NAD+ 2 FAD 2 ADP H2O Out: 6 NADH 2 FADH2 2 ATP CoA CO2 Fourth Pathway: Oxidative Phosphorylation: 1. Electron Transport Chain (ETC) 2. Chemiosmotic coupling Goal of ETC: create a proton/hydrogen gradient between the intermembrane space (IMS) and the mitochondrial matrix Mechanism: takes NADH and FADH2 (made in glycolysis, pyruvate oxidation, krebs cycle) → are oxidized (lose electrons) (donated to ETC) As electrons are removed → THIS RELEASES ENERGY Pump H+ ions from mitochondrial matric into intermembrane space Where do the electrons go? Puts all donated electrons onto Oxygen Oxygen serves as final electron acceptor Goal of chemiosmotic coupling: to create ATP Mechanism: H/protons move down gradient through ATP synthase → energy released from Hydrogen going through ATP synthase allows Pi + APD → ATP In: 10 NADH 2 FADH2 O2 34 ADP Out: 10 NAD+ 2 FAD H2O 34 ATP Calculate the total number of ATP produced via the complete oxidation of one glucose molecule Glycolysis: 2 ATP 2 NADH 0 FADH2 Pyruvate Oxifation: 0 ATP 2 NADH 2 FADH2 Krebs: 2 ATP 6 NADH 2 FADH2 Every 1 glucose produces 36 ATP What happens to the NADHs and FADH2 that were created during glycolysis, linking step, and Krebs Cycle? They become reduced in the electron transport chain within the intermembrane space. They become oxidized in the electron transport chain within the mitochondrial matrix. They become oxidized in the chemiosmotic coupling within the intermembrane space. They become reduced in the chemiosmotic coupling within the mitochondrial matrix. They become oxidized in the electron transport chain within the intermembrane space What region does the electron transport chain actively pump hydrogen ions into? Nucleus Mitochondrial matrix Cytoplasm Intermembrane space (from mitochondrial matrix INTO intermembrane space) Excess of glucose → covert glucose into glycogen via glycogenesis (liver or skeletal mm) OR convert into triglycerides via lipogenesis (adipose tissue (fat)) No glucose LIVER → glycogenolysis (glycogen into glucose) → OR glyconeogenesis (convert non-carbs into glucose) 1. Pyruvate 2. Glycerol 3. Lactate 4. Amino acids READING 4 Lipid Metabolism Lipogenesis: building lipids Glycerol + 3 Fatty Acids = triglycerides Occurs in adipose tissue and liver Excess glucose → glycolysis → pyruvate oxifation → excess acetyl CoA → fatty acids → triglycerides → adipose tissue OR live → cholesterol → steroid hormones → dependent on location → bile → liver (stored and concentrated in gallbladder) Lipolysis: break down triglycerides adipose tissue or liver Lipolysis and beta oxidation are rich sources of ATP. If your dietary intake included one fatty acid chain of 14 carbons, your body would produce approximately 114 ATP while the carbohydrate metabolism of a single glucose gives rise to approximately 36 ATP. Which type of metabolism produces more ATP? LIPID metabolism Ketogenesis → releases a lot of CO2 CO2 + ketones are acidic → blood concentration becomes acidic Metabolic acidosis (ketoacidosis) If lipid metabolism produces more ATP than carbohydrate metabolism, then why is glucose our primary energy currency? In other words, why is it utilized before fat metabolism? * Lipid metabolism produces ketones which can cause ketoacidosis (acidic blood) which would prevent proteins in the blood from functioning normally. 2/7/25 Protein Metabolism: What are the individual monomers of protein digestion and how do they cross the apical membrane of the epithelial cells of the small intestine? Glucose : Facilitated diffusion Amino acid : Co-transport with hydrogen ions Amino acid : Anti-transport with sodium ions Amino acid : Co-transport with sodium ions Proteogenesis: building of proteins from amino acids Lipogenesis: building of fats Gluconeogenesis: glucose → Some amino acids can be turned into pyruvate → pyruvate oxidation (skips glycolysis) Excess amino acids → transporters → amino acids (deaminate (remove NH2)) → urea → kidneys → excrete urea in urine (excess amino acids are released via urine) PUTTING IT ALL TOGETHER: Insulin is considered an anabolic, while glucagon is considered a catabolic hormone. * Anabolic: building blocks * Catabolic: breaks down stored molecules Absorptive state = fed state = when body is absorbing nutrients If actively absorbing nutrients, blood glucose levels increases and plasma amino acids levels increases this causes: The release of insulin from the beta cells of the pancreas How would these fx affect plasma con of glucose, fa, and aa → decrease because we are removing from blood into cells Post absorptive state = fasted state = no food intake * Not actively absorbing nutrients → glucose levels falls then release glucagon → from alpha cells of pancreas * Important to avoid hypoglycemia (low blood glucose) * Actions of glucagon * Alpha cells in pancreas: glucagon secretion * Liver: glycogenolysis, gluconeogenesis, ketone synthesis, protein breakdown * Adipose tissue: lipolysis, triglyceride synthesis 1. What causes glucagon secretion? Low blood glucose 2. What will happen to level of glucose in the blood? increase 3. What will happen to the level of fatty acids in the blood? Increase 4. Amino acids → increase 5. Were any fuel storages increased? No Intercellular Communication: How cells are able to communicate with each other How can you classify chemical messengers? Chemical only Structural only Functional only Chemical and functional Which of the following best characterizes hormones? Hormones are released by a neuron into the interstitial fluid and then targets a certain organ. Hormones are released by an endocrine gland and travel via a gap junction to an adjacent cell. Hormones are released by an endocrine gland via the axon terminal and travel through the synaptic cleft to reach their target cell. Hormones are released by an endocrine gland into the IF and then into the blood and then targets a certain organ CHEMICAL CLASSIFICATION: Amino Acid - neurotransmitter Amines - paracrines, neurotransmitter, Peptides/Proteins Steroids Which chemical classes are lipophilic? Steroids * Fat loving, can pass through cell membranes via simple diffusion * Not stored! * Release rate depends on how synthesis Which chemical classes are lipophobic? Amino acids, amines, peptide/proteins * Cannot use simple diffusion * Stored in secretory vesicles * Leave cell determine by exocytosis Amines (except thyroid hormone), peptide/proteins, amino acids are polar, while steroid hormones are non-polar. Amine synthesis: derived from amino acids Tryptophan → amine Through enzyme catalyzed reactions NEED TO KNOW Serotonin derived from tryptophan Melatonin derived from tryptophan Histamine derived from histidine Thyroid hormone derived from tyrosine Catecholamines derived from tyrosine Catecholamines: group of amines * Derived from tyrosine * Through ECR→ turn tyrosine into any catecholamine Peptide and protein synthesis: formed by cleaving larger proteins * Cleaves off aa Steroids: Start w cholesterol turn into steroid hormone NEED TO KNOW Start with cholesterol and use enzyme catalyzed reactions! 2/10/25 From secretory cell to target cell Transport → diffusion only through IF (AKA IF only) - nearby cells → diffusion through the IF first then blood borne transport (AKA IF and blood) - to far away cells * Bound to carrier protein * Dissolved in plasma Messenger Transport: * Diffusion through IF only * Secretory cell and target are nearby * Ligand is quickly degraded * Hydrophilic * Functional class: Paracrines, NTs, * Blood borne transport * Secretory cell and target are far away * Lipophobic (hydrophilic): dissolved in plasma * Chemical classes: peptide/proteins, amines * Lipophilic (hydrophobic): bound to a carrier protein * Chemical classes: steroids (& thyroid hormone) * Functional: hormones, neurohormones * 99% bound to a carrier protein * 1% dissolved in plasma * Simple diffusion Messenger half life How long it takes for 50% of messenger to be degraded Do messengers dissolved in plasma have a long or short half-life compared to messengers bound to carriers? Short half life What organ degrades these messengers and which organ excretes their breakdown products? Liver degrades Kidney breaksdown I'm a ligand that is transported through the interstitial fluid then blood. I am never bound to a carrier protein so I must be..... Lipophobic READING 2 - Intercellular Communication * Altering number receptors If we change # of receptors, we will change response If we change # of ligands, we will change response level What happened to the number of receptors? Based on what happened to the number of receptors would this cell have an increase in sensitivity or decrease in sensitivity to the ligand? Decrease, decreased (harder for ligand to find the receptor - sensitivity of target cell is correlation to # of receptors) Based on your response to the previous question, would this target cell have an increased response or decreased response to the ligand? Decreased Down Regulation and Up regulation Normal # of ligands = x level of response Double # of ligands = larger response We want normal response! (homeostasis obvi) Down regulation: when the body decreases # of receptors in response to having more ligands than normal Ex: drug tolerance Up regulation: when cells increase number of receptors in response to having to few ligands Signal Transduction Pathway: Signal molecule - chemical messenger - binds to Receptor protein - activates Intracellular signal molecules - alters Target proteins - create Response Intracellular mediated response - within cell * In cytoplasm or nucleus * Lipophilic (simple diffusion) * Chemical classes: steroids (& thyroid hormone) * Gene activation Membrane bound receptor mediated response - within the membrane * Lipophobic (doesnt have to get in cell) * Chemical classes: Amino acids, peptides/proteins, amines * Enzyme activation * Changes membrane permeability * Permeability of target to ions may be altered * Types: * Ligand linked: channel linked or g protein linked * Enzyme linked Types of channels Leak - always open Gated - open/close in response to stimuli * Voltage gated: change in response to a change in membrane potential * Chemically (ligand) gated: when ligands bind to them * - Mechanically gated: physically open/close by force * Thermally gated: changes in temperature Ligand gated channels: ligand must bind → Fast channels: when receptor and channel are same protein (ionotropic) → Slow channels: when receptor and channel are separate proteins (metabotropic) 2/12/25 I am a ligand that is made through a series of enzyme catalyzed reactions that starts with an amino acid so I must be a(n)...... Amine Peptide/protein (through protein synthesis) Steroid (ECR starting with cholesterol) Channel-linked receptors: fast ligated (can only open channels) Slow: channel and receptor are different proteins (need some type of protein) (g proteins link receptor and channel/enzyme) Structure of a g-protein: 3 subparts * At rest all 3 subunits are together & GDP attached to alpha subunit * To activate a g-protein: * Ligand has to bind to the receptor * GDP to fall off the alpha subunit * GTP attaches to alpha subunit * Causes alpha subunit with GTP to slide over (activate ion channel (open or close)) * To inactivate a g-protein: * Ligand has to fall off receptor * Hydrolyze alpha GTP → GDP * Alpha subunit with GDP returns back to beta and gamma units Slow g protein: 1. Direct coupling 1. Ligand binds to receptor 2. Activates g-protein - GDP falls off, GTP attaches, alpha unit with GTP slides over 3. Open or close a channel (allows ions to move in or stop ions from moving) 2. 2nd messengers 1. Triggered by first messenger (ligand) activating the g protein which actives an amplifier enzyme which activates 2nd messenger production which activates or inhibits cellular pathways 2. Two types: 1. Gi- inhibitory amplifier enzyme (decreases cell response) 2. Gs - stiulatory amplifier enzyme (increases cell response) cAMP: The cAMP second messenger system is used to reabsorb water from the kidneys back to the plasma. If water is not reabsorbed it is excreted in the urine. You are nurse at Normal Regional Hospital. A patient has arrived in the ER and is immediately diagnosed with hypothermia. What effect will this have on the this patient’s cAMP messenger system? Protein kinase A will not function properly and therefore PKA cannot activate cAMP and the patient will urinate profusely. The likelihood of vasopressin binding to the receptor is decreased causing increased activation of the G-protein. Adenylate cyclase will slow the conversion of ATP to cAMP resulting in a large volume of urine produced by the patient’s kidneys. The alpha-subunit will be slow to activate phosphatase. IP3/DAG/Ca: Cytokines are proteins that act as signaling messengers for your immune response. They are released from secretory cells to only act on nearby cells. Choose the CORRECT statement. Since cytokines are chemical messengers, they are functionally classified as hormones. (far away cells) Cytokines leave the secretory cell via simple diffusion. (exocytosis) Cytokines are derived from cholesterol. (protein synthesis) Cytokines will bind to receptors on the membranes of the nearby cells to initiate a signal transduction pathway to start a cell response. 2/14/25 How are the IP3/DAG systems turned off? 1. Ligand falls off receptor 2. Hydrolyze GTP → GDP 3. Dephosphorylate the protein 4. Degrade 2nd messenger (IP3, DAG) 5. Reuptake Ca Enzyme Linked Receptors: 1. Binds to receptor 2. Enzyme undergoes a conformational change (active) 3. Phosphorylate a protein 4. Protein casus cell response Ex: insulin receptor = tyrosine kinase Long distance communication: * Endocrine system * What chemical messenger: Hormones * Through what avenue must this messenger travel to reach target cell? * IF → blood → IF → receptor on target cell * Slower systems have a longer effect * Endocrine system is slower than nervous system * Nervous System * Two major cell types: neurons and glial cells * Are neurons capable of communicating short or long distances? Short * Uses chemical and electrical signals * Chemical: axon terminal at synaptic cleft * Electrical: axon * Uses voltage gates and ligand gated channels Nervous Communication: Dendrites - receive info via ligand channels Soma - “” Axon hillock - start an action potential Axon - propagate action potential Axon terminal- release neurotransmitters Axon hillock and axon have voltage gated channels Would a steroid hormone or a peptide/protein hormone bind to a receptor on the surface of the target cell? Steroid hormone - lipophilic - receptor will be in cell Peptide/protein hormone - lipophobic - receptor on the surface ENDOCRINE: 1. Hypothalamus will release a releasing hormone 2. RH travels to the anterior pituitary bind to excitatory receptor for RH = Erh 3. Anterior pituitary will synthesize and secrete stimulating hormones (SH) 4. SH travels through endocrine gland (binds to Esh 5. Causes endocrine gland to s/s fnal hormone 6. Hormone travels to target tissues/cells (bind Eh) 7. Cell response * Neurosecretory cells in the hypothalamus will release releasing hormones (neurohormones) * RH are release via exocytosis from axon terminals (lipophobic) * Travel in blood to anterior pituitary * RH will bind to excitatory receptors are on the endocrine receptor cells of anterior pituitary → s/s SH into the blood * SH will travel to the endocrine gland * Cause the cell response IF: hypothalamus releases inhibiting hormones → IH bind inhibitory receptors on anterior pituitary → causes ant pit to stop releasing hormones Feedback loops Control of endocrine systems - VIA NEGATIVE FEEDBACK (back to normal) Hypothalamus release tropic hormone 1 → bind to excitatory receptors (ant pit) → release tropic hormone 2 (SH) → travel to endocrine gland and bind to excitatory receptors → s/s final hormone → travel to target tissues and bind to Ehs → cell response To stop: bind to Ihs on ant pit to stop making tropic hormone 2, so we dont make final hormone EXAMPLE: Cortisol → stress hormone Stress → causes hypothalamus CRH secretion → ant pit (bind to excitatory receptors) → causes ant pit ACTH secretion (release via exocytosis (lipophobic)) travel in blood to → adrenal glands (binds to EATCH) → release of cortisol (final hormone) (release cortisol via simple diffusion (lipophilic)) → travel in blood to target tissues/cells → bind to excitatory receptors to cause cell response * Too much of cell response – eventually stops due to inhibitory receptors (stop releasing ATCH) 2/17/25 Control of endocrine systems Circadian rhythms controlled by time of day -melatonin When you stop releasing melatonin, you wake up Adenoma- benign tumor that forms on glands in the body Functioning: cause hypersecretion Nonfunctioning: cause hyposecretion If there was a non-functioning adenoma on the adrenal gland would cortisol by gland be hypo- or hypersecreted? Hyposecretion and primary disorder (because it is on the gland) If the adrenal gland atrophied, would cortisol be hypo- or hypersecreted? Hyposecreted Based on your response above, would the level of CRH be high or low? ACTH? Up If there was a functioning adenoma on the adrenal gland would cortisol be hypo- or hypersecreted? Hypersecreted Based on your response, would the levels of CRH be high or low? ACTH? Up, down, primary endocrine disorder READING 2 Oxytocin and ADH are synthesized in the posterior pituitary. True False Posterior pituitary is not a true endocrine gland Stored and released in posterior pituitary, hypothalamus makes them GROWTH HORMONE - peptide Hypothalamus releases gh (releasing hormone) travels to ant pit and binds to EGHRH which causes secretion of GH and binds to EGH on liver and causes secretion of IGF1 and bind to ET0F1 on target cells which causes cell response Hypothalamus releases gh (inhibitory hormone) which binds to IGHTH on ant pit which inhibits secretion of GH →cells throughout body → binds to EGH on cells throughout the body which causes cell response Where will the excitatory Growth Hormone Releasing Hormone receptors be located at? In the cytoplasm of the cells in the anterior pituitary In the membrane of the cells in the anterior pituitary In the cytoplasm of the cells in the liver In the membrane of the cells in the liver In 2003, FDA approved a use of recombinant human GH for treating children with non-GH deficient short stature (more than 2.25 standard deviations below the mean height for their age and sex). Average cost: $22,000 per year for hGH injections, this comes out to more than $33,000 per inch of height gained. Side effects: glucose intolerance and pancreatitis Hyposecretion of GH causes Dwarfism. Which of the following may explain hyposecretion of GH? Non-functioning pituitary adenoma Upregulation of GHRH receptors on the anterior pituitary Downregulation of GHRH receptors on the liver Atrophy of the hypothalamus THYROID HORMONE - amine Hypothalamus releases → TRH → binds to ETRH on ant pit → secretion of TSH → binds to ETH on thyroid gland s/s What type of receptors will thyroid hormone bind to? ​[Choose all that apply] Inhibitory receptors on the hypothalamus Excitatory receptors on the hypothalamus Excitatory receptors on the anterior pituitary Inhibitory receptors on the anterior pituitary Excitatory receptors on the thyroid gland Inhibitory receptors on the thyroid gland (And ETH on target tissues) Thyroid gland - releases 3 hormones: T3, T4, calcitonin C cells secret calcitonin Follicular cells secrete TH Follicular cells produce/secrete thyroglobin (precursor to TH) and bring iodide to the colloid. (iodid is brought into the follicular cells via AT from the blood) 2/19/25 Hypothyroidism - not making enough TH decrease BMR decrease HR Increase weight Decrease heat (cannot tolerate cold) Treatment: synthetic TH If lack TH from birth, cretinism (short, dwarfism, mentally underdeveloped) Hyperthyroidism - too much TH Increase BMR Increase HR Decrease weight Increase heat (cannot tolerate heat) You have a patient with a secondary hypersecretion disorder of the anterior pituitary. Indicate the levels TSH, TH, and TRH and diagnose the patient. TRH high ; TSH high ; TH high ; hypothyroidism TRH low ; TSH high ; TH high ; hyperthyroidism TRH high ; TSH high ; TH high ; hyperthyroidism Hypothalamus → TRH → ant pit → TSH → Thyroid gland → TH TRH low: Since TH (thyroid hormone) is high, it will exert negative feedback on the hypothalamus, suppressing TRH secretion. TSH high: The anterior pituitary is overproducing TSH, which is the hallmark of secondary hypersecretion. TH high: The thyroid gland responds to the high TSH levels by producing more thyroid hormone, leading to hyperthyroidism. READING 3 Adrenal Hormones What type of control regulates the synthesis/secretion of parathyroid hormone and calcitonin? (both Ca regulation (in the plasma)) Humoral control Hormonal control Neural control Adrenal glands - sit on top of the kidneys 2 major layers - adrenal cortex (outer), adrenal medulla (inner) Zona glomerulosa: secretes mineralcotricoids (adrenocorticoids) Steroid = lipophilic * Aldosterone * Target: kidneys * Fxn: reabsorption of Na and K excretion Zona fasciulata : cortisol Zona reticularis: sex hormones How would the majority of aldosterone be transported in blood? Bound to a carrier protein Dissolved in plasma Chemical class = steroid = lipophilic = bound to carrier protein Control of aldosterone: Steroid hormone controlled via humoral control S/s of aldosterone - Increase Na in blood, decrease K in blood Cortisol: Steroid - hypothalamic - CRH, ATCH = peptide Adrenocorticotropic hormone will be converted to cortisol. True False Causes release of cortisol (peptide via protein synthesis) Cortisol - steroid from cholesterol Thymus - involved in immune response Secretes thymosin * Regulate t cell function (type of WBC) * Cortisol suppresses the thymus Adrenal medulla Secretory cells = chromafin cells = modified neurons Secrete: 80% epi, 20% norepinephine, 1% dopamine (ALL amines, all catecholamines, LIPOPHOBIC) Under neural control Epi causes: gluconeogenesis, glycogenolosis, lipolysis, ketogenesis INCREASE fuel substrates (adrenaline during fight/flight) PINEAL GLAND: Glandular tissue in brain Secrete melatonin * Amine - tryptophan * Circadian rhythms (sleep schedule) GONADS: male- testes * Testosterone: steroid * androstenedione Female - ovaries Testosterone: Hypothalamus secretes GnRH to ant pit