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Biology 212 – Principles of Human Physiology Fall 2015 REVIEW SHEET FOR WEEKS #14 (material for inclass Exam #1) Disclaimer: You will be tested on your understanding of all material covered in lecture, on the textbook’s information with respect to the topics covered in lecture, and on the following specific textbook pages: Ch. 1 (entire chapter), Ch. 2 (cell structures and organelles; exocytosis and endocytosis), p. 59 (cystic fibrosis), p. 72 (exercising muscles), pp. 7577 (vesicular transport exocytosis and endocytosis), p. 611 (oral rehydration therapy and cholera), pp. 630635 (thermoregulation), and pp. 689699 (insulin, glucagon, diabetes). 1. (From lecture and text): Know levels of organization in body (atoms, molecules, cells, etc.) Define lumen. Know properties and examples of epithelial tissue, connective tissue, exocrine glands, endocrine glands. atoms→ molecules→ cells→ tissues→ organs→ organ systems Lumen→ the interior space of a hollow organ or tube Epithelial tissue→ protection, secretion, absorption. Ex: the skin can exchange little between the body and outside environment, making it a protective barrier. By contrast the epithelial cells lining the small intestine of the digestive tract are specialized for absorbing nutrients that have come from outside the body. Connective tissue→ structural support. Ex: it includes such diverse structures as the loose connective tissue that attaches epithelial tissue to underlying structures; tendons, which attach skeletal muscles to bones; bone, which gives the body shape, support, and protection; and blood, which transports materials from one part of the body to another. Exocrine glands→ during development, if the connecting cells between the epithelial surface cells and the secretory gland cells within the depths of the pocket remain intact as a duct between the gland and the surface, an exocrine gland is formed. They secrete through ducts to the outside of the body (or into a cavity that opens to the outside) (exo means “external”; crine means “secretion”). Ex: sweat glands and glands that secrete digestive juices. Endocrine glands→ If, in contrast, the connecting cells disappear during development and the secretory gland cells are isolated from the surface, an endocrine gland is formed. Endocrine glands lack ducts and release their secretory products, known as hormones, internally into the blood (endo means “internal”). Ex: the pancreas secretes insulin into the blood, which transports this hormone to its sites of action throughout the body. Most cell types depend on insulin for taking up glucose (sugar). 2. Define: homeostasis, extracellular fluid, intracellular fluid. What is the “internal environment” which is maintained in homeostasis? What are the two main compartments of the ECF? What is the third, smaller compartment of ECF? Homeostasis→ maintaining equilibrium, processes in the body to maintain a relatively stable internal environment (controlled by lower parts of the brain automatically). Controlling body temperature; maintaining right amount of water, pH blood, sodium, potassium, etc. Extracellular fluid (ECF)→ internal environment of body, body that surrounds cells Intracellular fluid (ICF)→ inside the cell ECF is the internal environment maintained in homeostasis 2 main components of ECF→ interstitial fluid (fluid in tissues; surrounds and bathes the cells), plasma (in blood cells; fluid portion of the blood) 3rd smaller component of ECF→ transcellular fluid 3. (From lecture and text): Understand and be able to identify: negative feedback, positive feedback, feedforward control. Which of these is more common? Know the terms: set point, effector, sensors (receptors), integrating center. Contrast intrinsic and extrinsic controls. Negative feedback→ self-regulating process; a change in a homeostatically controlled factor triggers a response that seeks to restore the factor to normal by moving the factor in the opposite direction of its initial change. Homeostatic processes operate under negative feedback. Ex: blood sugar (glucose) is high, so the pancreas releases hormones and they’re sent into the bloodstream. *most common* Positive feedback→ self propagating; the output enhances or amplifies a change so that the controlled variable continues to move in the direction of the initial change. Ex: nerve impulse, childbirth (stretches cervix) Feed forward control→ reflexes that enable the body to predict that a change is about to occur and start the response loop in anticipation of the change. Ex: when a meal is still in the digestive tract, a feedforward mechanism increases secretion of a hormone (insulin) that promotes the cellular uptake and storage of ingested nutrients after they have been absorbed from the digestive tract. This anticipatory response helps limit the rise in blood nutrient concentration after nutrients have been absorbed. Setpoint→ desired value (normal value). Ex: desired temperature level Effector→ the component of the control system commanded to bring about the desired effect (bring variable back to what it’s supposed to be). Ex: the furnace Sensors (receptors)→ detect the change in the variable; which monitors the magnitude of the controlled variable. The sensor typically converts the original information regarding a change into a “language” the control system can “understand.” Ex: the thermometer Integrating center→ also known as control center; it compares the sensor’s input with the set point and adjusts the heat output of the furnace to bring about the appropriate response to oppose a deviation from the set point. Ex: the thermostat Intrinsic controls→ also known as local controls, are built into or are inherent in an organ (intrinsic means “within”). Ex: as an exercising skeletal muscle rapidly uses up to generate energy to support its contractile activity, the concentration within the muscle falls. This local chemical change acts directly on the smooth muscle in the walls of the blood vessels supplying the exercising muscle, causing the smooth muscle to relax so that the vessels dilate, or open widely. As a result, increased blood flows through the dilated vessels into the exercising muscle, bringing in more. This local mechanism helps maintain an optimal level of in the fluid immediately around the exercising muscle’s cells. Extrinsic controls→ most factors in the internal environment are maintained, however, by extrinsic, or systemic, controls, which are regulatory mechanisms initiated outside an organ to alter the organ’s activity (extrinsic means “outside of ”). Extrinsic control of the organs and body systems is accomplished by the nervous and endocrine systems, the two major regulatory systems. Extrinsic control permits coordinated regulation of several organs toward a common goal; in contrast, intrinsic controls serve only the organ in which they occur. 4. (From lecture and text): Know thermoregulation in the body: Where is the body’s thermoregulation center (thermostat)? Where are the body’s thermoreceptors, and what does each type specifically monitor? What are the effectors? Explain the body’s response to cold exposure and a drop in core body temperature. What is nonshivering thermogenesis, and where in the body does this process occur? (Contrast the role of the mitochondrion in this process to its role in glucose metabolism.) Explain the body’s response to heat exposure and an increase in core body temperature. In the context of the thermoregulation system, explain what pyrogens are and how a “fever” occurs. What is heat exhaustion? heat stroke? What is hypothermia? What is hyperthermia? The body’s thermoregulation center (thermostat)→ located in the hypothalamus The body’s thermoreceptors→ they’re in the skin, body core, and hypothalamus. They are specialized nerve cells that are able to detect differences in temperature. Temperature is a relative measure of heat present in the environment. Thermoreceptors are able to detect heat and cold, and are found throughout the skin in order to allow sensory reception throughout the body. First, heat receptors are closer to the skin's surface, while cold receptors are found deeper in the dermis. This means that sensitivity to hot temperatures will be higher than lower temperatures based on the location. Additionally, different sections of the skin will have more receptors than others. The hand, for example, has more thermoreceptors than the thigh or shin, which means it will be more sensitive to temperature changes. Effectors→ sweat glands, blood vessels, shivering (skeletal muscles) Body’s response to cold exposure→ redirects blood flow from the skin to the internal organs- shifts heat from extremities. Shivering (using skeletal muscles so heat is released), vasoconstrict blood vessels in the skin and vasodilate vessels in core (keep heat in where heart, lungscore are). Nonshivering thermogenesis→ is mediated on cold exposure by the sympathetic nervous system, which increases heat production by stimulating brown adipose tissue, or brown fat, a special type of adipose tissue that is especially capable of converting chemical energy from food into heat. In humans, it is most important in newborns, who have prominent deposits of brown fat. Unlike the ordinary white adipose tissue that stores energy in the form of triglyceride deposits, brown adipose tissue acts like a furnace that burns energy to generate heat. Newborns use brown fat to keep warm because they cannot shiver. Brown fat is brown in color because it has an abundance of mitochondria that contain iron, which causes the tissue to appear reddish brown. The mitochondria of brown fat contain a unique uncoupling protein called thermogenin (“heat producer”) that uncouples the electron transport system from the process of generating ATP (see Oxidative Phosphorylation) during oxidation of glucose and fatty acids. Instead of some of the energy released by the electron transport system being harnessed in ATP by chemiosmosis, all of the energy is dissipated as heat. Body’s response to heat exposure→ sweating (releases liquid onto your skin and to evaporate it uses up the heat, so it brings the temp. down), vasodilate blood vessels in the skin (more blood is going to the skin, so when blood goes to the surface the heat is released) Pyrogens and how a “fever” occurs→ pyrogens are small molecules that reset the thermostat to a higher temperature. In a fever, pyrogens are released and reset the thermostat to a higher temp. (39 c). The body then begins shivering (chills) which generates heat, and it also redirects blood flow away from the skin (pale) to the core. Benefits of a fever include: speeds up metabolism, and germs can’t survive at such a high temp. Heat exhaustion→ is a state of collapse, usually manifested by fainting, that is caused by reduced blood pressure brought about as a result of overtaxing the heatloss mechanisms. Thus, heat exhaustion is a consequence of overactivity of the heatloss mechanisms rather than a breakdown of these mechanisms. Because the heatloss mechanisms have been very active, body temperature is only mildly elevated in heat exhaustion. By forcing cessation of activity when the heatloss mechanisms are no longer able to cope with heat gain through exercise or a hot environment, heat exhaustion serves as a safety valve to help prevent the more serious consequences of heat stroke. Heat stroke→ is an extremely dangerous situation that arises from the complete breakdown of the hypothalamic thermoregulatory systems. Heat stroke is more likely to occur on overexertion during a prolonged exposure to a hot, humid environment. Hypothermia→ a fall in body temperature, occurs when generalized cooling of the body exceeds the ability of the normal heatproducing and heatconserving regulatory mechanisms to match the excessive heat loss. As hypothermia sets in, the rate of all metabolic processes slows because of the declining temperature. Hyperthermia→ any elevation in body temperature above the normally accepted range; no sweating occurs, despite a markedly elevated body temperature, because the hypothalamic thermoregulatory control centers are not functioning properly and cannot initiate heatloss mechanisms. 5. Know the “basics” of blood sugar regulation in the body (from lecture, pp. 689699, and iLearn handouts): Which molecule is “blood sugar”? In humans, which complex carbohydrate is the storage form for this blood sugar? How does the body maintain blood sugar levels within a normal range, and what type of feedback control is involved? Big picture …What is the role of insulin? Details … From which cells, and from which organ, does insulin come, and what stimulates its release? Which body cells respond to insulin (and how do these cells “know” that insulin is there)? What do the responding cells do when insulin arrives? (For example, what is GLUT4 and what is transporter recruitment?) Thinking question … why would it evolve that brain cells do not rely on insulin signals for glucose transport? Big picture …What is the role of glucagon? Details … From which cells, and from which organ, does glucagon come, and what stimulates its release? What do the responding cells do when glucagon arrives? “Blood sugar”→ glucose Complex carbohydrate storage form of glucose→ glycogen How the body maintains blood sugar levels within a normal range→ *negative feedback* if blood sugar levels are too high= beta cells in Islet of Langerhans in pancreas detect high levels, release insulin into the bloodstream, insulin binds to insulin receptors (liver, skeletal musclefat cells and adipose tissue), liver and muscle cells store glucose as glycogen, adipose cells store glucose as fat if blood sugar is too low= alpha cells in Islet of Langerhans in pancreas detect low blood sugar levels, release glucagon into the bloodstream, cells that have glucagon receptors are liver (chops up glycogen to make glucose and lets glucose back out into the bloodstream) and fat cells (breaking down fat, glucose is sent into bloodstream). What is the role of insulin→ Insulin comes from Beta cells in the pancreas; high blood sugar stimulates its release Adipose tissue (fat cells), skeletal muscle (muscle cells), and liver cells respond to insulin and they know it’s is there because they have insulin receptors When insulin arrives the responding cells use the carrier protein GLUT4 to transport glucose. GLUT4 protein binds to the membrane and recruits more carrier proteins to increase the rate of diffusion (takes more glucose into the cell from the bloodstream). Transporter recruitment→ the phenomenon of inserting additional transporters (carriers) for a particular substance into the plasma membrane, thereby increasing membrane permeability to the substance, in response to an appropriate stimulus. Brain cells do not rely on insulin signals for glucose transport because it works off transport recruitment, such as exercising muscle cells do. Exercising muscle cells don’t respond to insulin, so it puts more GLUT4 proteins into the membrane on its own (take in more glucose because your muscle cells need more energy when you’re working out). Similarly, our brain cells constantly need energy b/c it controls all of our body functions. What is the role of glucagon→ Glucagon comes from Alpha cells in the pancreas; low blood sugar stimulates its release When glucagon arrives the responding cells send glucose back into the bloodstream. Liver (chops up glycogen to make glucose and lets glucose back out into the bloodstream), Adipose tissue (break down stored fat into fatty acids for use as fuel by cells). 6. (From lecture and text): Know diabetes mellitus – know the different types (Type 1, Type 2); for each, know typical age of onset, what the defect is in each case, how each is treated, new approaches to treatment. Which type of diabetes is most common? Diabetes Mellitus→ high rate of glucagon secretion concurrent with insulin insufficiency because the elevated blood glucose cannot inhibit glucagon secretion as it normally would; a metabolic disorder characterized by abnormally high blood glucose concentrations. Type 1→ diagnosed in childhood usually and have it for the rest of their life. Issue is that they do not make insulin; Beta cells aren’t making insulin. Mainly thought that it is an autoimmune disease. Have very high blood sugar and have to test their own blood sugar throughout the day. They’re taking insulin and determine how much insulin based on how high or low their blood sugar is (maintaining homeostasis). Type 2→ *most common* usually diagnosed in adults. Linked to diet, lifestyle, being overweight, and genetic component (runs in families). The individuals make insulin, but the body cells do not respond to it. The issue is the body cells, because they don’t have the receptors, so they can’t recognize the insulin; the sugar stays out in the blood, so blood sugar is high. Solution: try and fix lifestyle, medications to increase sensitivity of the cells. Exercising because it helps control blood sugar by placing GLUT-4 proteins in the membrane without having to intake more sugar. 7. (From text): Review functions of the following organelles and cell structures: cell membrane, nucleus, mitochondria, cytoplasm, cytoskeleton, ribosomes, rough ER, smooth ER, transport vesicles, Golgi complex, lysosomes, secretory vesicles, peroxisomes. Cell membrane→ property is hydrophobic, and it is semi-permeable; thin membranous structure that encloses each cell and is composed mostly of lipid (fat) molecules and studded with proteins, carbohydrates, and cholesterol. Bilayer of phospholipid molecules that acts as a gateway between ECF and ICF Nucleus→ it is surrounded by a doublelayered membrane, the nuclear envelope, which separates the nucleus from the rest of the cell. The nuclear envelope is pierced by many nuclear pores that allow necessary traffic to move between the nucleus and the cytoplasm. The nucleus houses the cell’s genetic material, deoxyribonucleic acid (DNA), which, along with associated nuclear proteins, is organized into chromosomes. Mitochondria→ are the energy organelles, or “power plants,” of the cell; they extract energy from the nutrients in food and transform it into a usable form for cell activities. Mitochondria generate about 90% of the energy that cells—and, accordingly, the whole body —need to survive and function. Cytoplasm→ that portion of the cell interior not occupied by the nucleus. It contains a number of discrete, specialized organelles (the cell’s “little organs”) and the cytoskeleton (a scaffolding of proteins) dispersed within the cytosol (a complex, gellike liquid). Cytoskeleton→ an interconnected system of protein fibers and tubes that extends throughout the cytosol. This elaborate protein network gives the cell its shape, provides for its internal organization, and regulates its various movements, thus serving as the cell’s “bone and muscle.” Ribosomes→ Granules of RNA and proteins—some attached to rough ER, some free in cytosol; nonmembranous organelles, carry out protein synthesis by translating mRNA into chains of amino acids in the ordered sequence dictated by the original DNA code. Rough ER→ synthesizes proteins for secretion and membrane construction Smooth ER→ synthesis of fatty acids, steroids and lipids; contains enzymes specialized for detoxifying harmful substances produced within the body by metabolism or substances that enter the body from the outside in the form of drugs or alcohol Transport vesicles→ Membranous sac enclosing newly synthesized proteins that buds off the smooth endoplasmic reticulum and moves the proteins to the Golgi complex for further processing and packaging for their final destination Golgi complex→ Modifies, packages, and distributes newly synthesized proteins Lysosomes→ Serve as cell’s digestive system, destroying foreign substances and cellular debris Secretory vesicles→ Membrane-enclosed sacs containing proteins that have been synthesized and processed by the endoplasmic reticulum and Golgi complex of the cell and which are released to the cell’s exterior by exocytosis on appropriate stimulation Peroxisomes→ are membranous organelles that produce and decompose hydrogen peroxide in the process of degrading potentially toxic molecules (peroxi refers to “hydrogen peroxide”). They too arise from the ER and Golgi complex. 8. Know adenosine triphosphate (ATP). How does ATP provide energy to the cell? How and where does the cell make ATP? What is the relationship between ATP and ADP? ATP→ is the universal energy carrier—the common energy “currency” of the body. Cells can “cash in” ATP to pay the energy “price” for running the cell machinery. To obtain immediate usable energy, cells split the terminal phosphate bond of ATP, which yields ADP. ATP provides energy for a cell by storing energy in the bond between the second and third phosphate group; when the highenergy bond that binds the terminal phosphate to adenosine is split, a substantial amount of energy is released. The cell makes ATP from the sequential dismantling of absorbed nutrient molecules in three stages: glycolysis in the cytosol, the citric acid cycle in the mitochondrial matrix, andoxidative phosphorylation at the mitochondrial inner membrane (cristae). ATP has one more phosphate group than ADP 9. (See iLearn handout) Know glycolysis; pyruvate metabolism, especially comparing the results during times when oxygen is available (aerobic), and times when oxygen is limited (anaerobic); pyruvic acid’s conversion to acetyl CoA; Krebs cycle (citric acid cycle); electron transport chain (oxidative phosphorylation) – where specifically does each process occur? what are starting substances and endproducts of each process? how many net ATP are produced in each process? how many FADH an2 NADH molecules are produced in each process? what is the purpose of FADH 2nd NADH? which processes stop if there is no oxygen? Thinking questions … a) When a cell doesn’t have many mitochondria, what would be the primary purpose for this cell to convert pyruvate to lactic acid? b) Later, if the cell can make more mitochondria, some of the lactic acid is converted back to pyruvate. Explain this in terms of the Law of Mass Action. (If necessary, review Law of Mass Action on p. 472.) Glycolysis→ set of 10 chemical reactions; happens in cytoplasm, started with glucose and ends up with 2 pyruvate molecules. In order for this to happen, we need 2 molecules of NAD (picks up high energy electrons), so we end up with 2 NADH+. Need 2 ADP (building blocks to make ATP) → need 2 ATP to kickstart glycolysis, but we make 4, so we have 2 additional ATP molecules. Pyruvate (3 carbon molecules) moves into the mitochondria (mitochondrial matrix). It then has to be converted into Acetyl coA; 2 NADH (holding high energy electrons) created. Krebs Cycle→ Pyruvate has 3 carbons, but Acetyl coA only has 2, so the 3rd carbon becomes carbon dioxide (Co2)- gets ride of the last carbon. 2 Acetyl coA goes through the Krebs cycle (in the mitochondrial matrix); create 6 NADH, 2 FADH, create 4 Co2 (what we breathe out), make 2 ATP. Electron Transport Chain→ all these high energy electrons go through the electron transport chain; occurs in cristae of mitochondria (folds) ; enzymes are built onto the cristae membrane structure. Electrons from FADH and NADH drop of electrons at a protein and pass them onto other proteins. As they transport down the chain, their high energy is being harnessed and being put into ATP makes a lot of ATP). The system recycles NAD; NADH and FADH2 get rid of their electrons so they go back to NAD & FAD. Final electron acceptor is O2, as electrons go down the chain, they get attached to oxygen and it creates water (breathe in O2, then the body uses oxygen to make ATP and we breathe out CO2). Without oxygen, Krebs cycle and e- chain (e-chain creates NAD + FAD) can’t happen; the e-chain will not happen, so that means no ATP; the krebs cycle shuts down b/c we are not going to be making NAD & FAD to restart the cycle. They can’t get rid of their high energy electrons, so it causes back up b/c we aren’t getting the NAD & FAD needed. Glycolysis continues working, it is not 100% dependent on getting NAD from the e-chain; we can get NAD from somewhere else to run glycolysis. Pyruvate don’t go into mitochondria, so they stay in the cytoplasm & become lactic acid. Pyruvate → lactic acid (anaerobic) uses NADH to convert pyruvate to lactic acid (NAD+). Pyruvate regenerates NAD+ from NADH; only get 2 ATP when O2 is not available. No O2= pyruvate in cytoplasm goes up. If oxygen becomes available, some of the lactic acid will be converted back to pyruvate b/c O2 present= pyruvate moves into the mitochondria, which means the amount in the cytoplasm goes down & lactic acid creates more pyruvate. Law of Mass Action→ rate of the reaction depends on the amount of the reactant or the product, keeping a balance b/w reactants and products. 10. Describe the fluid mosaic model of the cell membrane, and the locations and roles of each molecule type: phospholipids, proteins, cholesterol, carbohydrates. Understand the concepts of polar vs. nonpolar molecules, hydrophilic vs. hydrophobic. Fluid mosaic model of cell membrane→ “fluid” (everything in cell membrane is moving) “mosaic” (proteins) Phospholipid→ primary molecule and assemble into a phospholipid bilayer; made of two fatty acid chains and a phosphate group, phosphate head is polar and hydrophilic, fatty acid tail is nonpolar and hydrophobic Proteins→ second molecule; different shapes & sizes. Glycoproteins receptors to receive signals; involved in cell identification (which are yours and not yours). Integral Proteins=extend all the way across membrane, hydrophobic. Peripheral proteins=attach loosely to integral proteins or polar heads of membrane Cholesterol→ basic building blocks contributes to both the fluidity and the stability of the membrane. Cholesterol molecules are tucked between the phospholipid molecules, where they prevent the fatty acid chains from packing together and crystallizing, a process that would drastically reduce membrane fluidity. Carbohydrates→ only on ECF side “sugar coating” the cells. Short carbohydrate chains protrude like tiny antennas from the outer surface, bound primarily to membrane proteins and, to a lesser extent, to lipids. These sugary combinations are known as glycoproteins (receptors to receive signals; involved in cell identification which are yours and not yours) and glycolipids, respectively, and the coating they form is called the glycocalyx. Polar vs. Nonpolar→ phospholipids have a polar (electrically charged) head containing a negatively charged phosphate group and two nonpolar (electrically neutral) fatty acid chain tails. Hydrophilic vs. Hydrophobic→ hydrophilic mixes with water (polar head) and hydrophobic doesn’t mix with water (nonpolar tail) 11. Know the various functions of the membrane. Besides acting as a mechanical barrier that traps needed molecules within the cell, the plasma membrane helps determine the cell’s composition by selectively permitting specific substances to pass between the cell and its environment. The plasma membrane controls the entry of nutrient molecules and the exit of secretory and waste products. In addition, it maintains differences in ion concentrations inside and outside the cell, which are important in the membrane’s electrical activity. The plasma membrane also participates in the joining of cells to form tissues and organs. Finally, it plays a key role in enabling a cell to respond to signals from chemical messengers in the cell’s environment; this ability is important in communication among cells. 12. Define, distinguish, and know purpose of: desmosomes, tight junctions, and gap junctions. Know examples of where each type of cell junction might be found. Which cell junction consists of connexons? Which cell junction involves cadherins? Which type of junctions are “communicating junctions”? Desmosomes→ proteins (cadherins) interlock with each other and creates this network of proteins which hold the cell together. Allows some flexibility; tend to have them in tissues that have to stretch, such as the heart (beats & relaxes). strongest cellcell junction. Ex: skin, the heart, and the uterus Tight Junction→ found in epithelial tissue sheets of cells (touching each other) protein structure that’s holding the cell together; covering the outside and lining the inside. Protections through tight junctions so that nothing could leak; no gaps, they’re fused together. Gap junction→ proteins on left & right line up and create a connexon (hollow in the inside) create this hollow tube so ions & molecules can pass through. Allow communication b/w the two cells; Ex: cardiac muscle (heart) and smooth muscle 13. Understand the concept of membrane permeability. What is meant by semipermeable or selectively permeable? Selectively permeable→ It permits some particles to pass through while excluding others; property of cell membrane is hydrophobic, so molecules w/ a charge are going to be harder to get in, such as water. Two properties of a molecule influence permeability→ size of molecule and lipid solubility 14. Define concentration gradient. Define net movement. Define equilibrium (in terms of movement of molecules). Concentration gradient→ a diference in concentration of a particular substance between two adjacent areas; but the net movement of molecules by difusion is from the area of higher concentration to the area of lower concentration. Net movement→ the diference between the opposing movements of two types of molecules in a solution; if 10 molecules move from area A to area B while 2 molecules simultaneously move from B to A, the net diffusion is 8 molecules moving from A to B. Molecules spread in this way until the substance is uniformly distributed between the two areas and a concentration gradient no longer exists Equilibrium→ at this point, even though movement is still taking place, no net diffusion is occurring because the opposing movements exactly counterbalance each other. Movement of molecules from area A to area B is exactly matched by movement of molecules from B to A. 15. Understand the different types of membrane transport (see Table 32 on p. 78): channel proteins vs. carrier proteins, simple diffusion across the phospholipid bilayer, facilitated diffusion, primary active transport, secondary active transport, osmosis. Which of these types of transport are passive? Which types are in the category of “carriermediated transport”? What is symport (cotransport), and what is antiport (countertransport)? (With which type of transport are these terms used?) Channel protein→ spans all the way across the membrane; hollow down the inside. small, Passive; ions move down electrochemical gradient through open channels (from high to low concentration and by attraction of ion to area of opposite charge); Specific small ions (e.g.,Na+, K+, Ca2+, Cl). Channels are highly selective. Some channels are leak channels that always permit passage of their selected ion. Others are gated channels that may be open or closed to their specific ion as a result of changes in channel shape in response to controlling mechanisms. Carrier protein→ only open on one side at a time; Transport of a substance across the plasma membrane facilitated by a carrier molecule. Bind with specific substrates and carry them across membrane by changing conformation, can move larger molecules than channel proteins can. Slower rate than simple difusion, but still selective. Simple diffusion through lipid bilayer→ Passive; molecules move down concentration gradient (from high to low concentration); Nonpolar molecules of any size (e.g., O2, CO2, fatty acids); Continues until gradient is abolished (dynamic equilibrium with no net difusion) Facilitated diffusion→ Passive & carrier-mediated transport; molecules move down concentration gradient (from high to low concentration). Specific polar molecules for which carrier is available (e.g., glucose); Displays a transport maximum; carrier can become saturated Primary active transport→ Active & carriermediated transport; ions move against concentration gradient (from low to high concentration); requires ATP. Na+/K+ pump that pumps 3 Na+ out and 2 K+ into the cell. Specific cations for which carriers are available (e.g.,Na+, K+, H+, Ca2+). Displays a transport maximum; carrier can become saturated Secondary active transport→ Active & carrier-mediated transport; substance moves against concentration gradient (from low to high concentration); driven directly by ion gradient (usually ) established by ATP-requiring primary pump. In symport, cotransported molecule and driving ion move in same direction; in antiport, transported solute and driving ion move in opposite directions. Specific polar molecules and ions for which coupled transport carriers are available (e.g., glucose, amino acids for symport; some ions for antiport). Displays a transport maximum; coupled transport carrier can become saturated Osmosis→ Passive; water moves down its own concentration gradient (to area of lower water concentration—that is, higher solute concentration); Water only. Continues until concentration difference is abolished or until stopped by opposing hydrostatic pressure or until cell is destroyed. 16. What are the primary factors which control the rate of simple diffusion across the cell membrane? Know all of the variables in Fick’s Law, the consequences of hydration shells, and the concept of partition coefficient. Understand the concept of membrane permeability. Primary factors which control rate of diffusion→ ↑ Concentration gradient of ↑ substance (ΔC) ↑ Surface area of membrane (A) ↑ ↑ Lipid solubility (β) ↑ ↑ Molecular weight of substance (MW ↑ ↑ Distance (thickness) (ΔX) ↓ Fick’s Law→ Delta C= difference in concentration; A= surface area; MW= molecular weight; Delta X= distance; Beta= lipid solubility Hydration shells→ Na+ atomic number is 11, and K+ is 19. So, w/o water (non hydrated radius) Na is 0.9 (more dense) and K is 1.3 (more dilute). Positive ions ends up with a hydrated shell of water around the ion as its moving around. Na+ gathers a larger shell around it than K+ does. Density of surface area charge in Na+ is more dense, so it attracts greater electrical charge. K+ will move faster throughout the body because it is smaller. (Larger particle= slower rate of diffusion) Partition coefficient→ lipid soluble/ water soluble this ratio, then you get a number. More lipid soluble= bigger partition coefficient= faster rate of diffusion. Lower partition coefficient= slower rate of diffusion. Membrane permeability→ Beta, MW, and Delta X all contribute to membrane permeability. Two properties of particles influence whether they can permeate the plasma membrane without assistance: 1. the relative solubility of the particle in lipid and 2. the size of the particle. Highly lipidsoluble particles of any size can dissolve in the lipid bilayer and pass through the membrane 17. Know properties of channel proteins: Are channel proteins specific? Do channel proteins typically get saturated? What substances are transported through channels? Distinguish between leak (open) channels and gated channels. For gated channels, what controls whether the gate is opened or closed? Channel proteins are waterfilled pathways through the lipid bilayer Watersoluble substances small enough to enter a channel can pass through the membrane by this means without coming into direct contact with the hydrophobic lipid interior. Channels are highly selective. Only small ions can fit through channels leak channels always permit passage of their selected ion; open all the time. gated channels may be open or closed to their specific ion as a result of changes in channel shape in response to controlling mechanisms. Some gated channels are chemically gated, chemical determines whether its opened or closed (ligands bind); others are voltagegated (open and close depending on electrical properties of membrane); others are mechanically gated (open and close depending on some mechanical force like pressure) 18. (From text): Know cystic fibrosis (CF): how does one get it? what are the symptoms? Why does the person develop those symptoms? (In other words, what is the specific defect in CF, and how does it result in the symptoms observed?) What treatments are employed or are being investigated? What the most common fatal genetic disease in the United States, strikes 1 in every 2000 Caucasian children. It is characterized by the production of abnormally thick, sticky mucus. Most dramatically affected are the respiratory airways and the pancreas; normally forms the CL channels in the plasma membrane; Cystic fibrosis (CF) is a genetic disease that affects the viscosity of mucous in the lungs and digestive system, affecting not only the lungs, but also the pancreas, liver and intestines. The patient suffers from chronic respiratory infections and generalized malnutrition. How caused by one of a number of genetic defects; CF, the defective CFTR gets “stuck” in the endoplasmic reticulum–Golgi system, which normally manufactures and processes this product and then ships it to the plasma membrane. In patients with CF, the mutated version of CFTR is only partially processed and never makes it to the cell surface. The resultant absence of CFTR protein in the plasma membrane makes the membrane impermeable to Cl symptoms repeated respiratory infections, why develop symptoms/specific defect in CF The presence of thick, sticky mucus in the respiratory airways makes it difficult to get adequate air in and out of the lungs. Also, because bacteria thrive in the accumulated mucus, patients with CF experience repeated respiratory infections. They are especially susceptible to Pseudomonas aeruginosa, an “opportunistic” bacterium that is often present in the environment but usually causes infection only when some underlying problem handicaps the body’s defenses. Gradually, the involved lung tissue becomes scarred (fibrotic), making the lungs harder to inflate. This complication increases the work of breathing beyond the extra effort required to move air through the clogged airways. Pancreas produces enzymes important in the digestion of food, malnourishment eventually results. In addition, as the pancreatic digestive secretions accumulate behind the blocked duct, fluidfilled cysts form in the pancreas, with the affected pancreatic tissue gradually degenerating and becoming fibrotic. treatments physical therapy and mucusthinning aerosols to help clear the airways of excess mucus and antibiotic therapy to combat respiratory infections, plus special diets and administration of pancreatic digestive enzymes to maintain adequate nutrition 19. Know properties of carrier proteins: How are they different from channel proteins? Are carrier proteins specific? Do they get saturated? For a particular cell, how can the rate of transport via a specific carrier protein be increased? (For example, see p. 72, p. 691, and figure on iLearn: how does resting skeletal muscle increase glucose transport? How does exercising muscle increase glucose transport? Making a connection … Why is exercise an important treatment for diabetes?) carrier they transfer across the membrane specific substances that are unable to cross on their own. Each carrier can transport only a particular molecule (or ion) or group of closely related molecules. channel proteins vs carrier proteins Channel protein→ spans all the way across the membrane; hollow down the inside. small, Passive; ions move down electrochemical gradient through open channels (from high to low concentration and by attraction of ion to area of opposite charge); Specific small ions (e.g.,Na+, K+, Ca2+, Cl). Channels are highly selective. Some channels are leak channels that always permit passage of their selected ion. Others are gated channels that may be open or closed to their specific ion as a result of changes in channel shape in response to controlling mechanisms. Carrier protein→ only open on one side at a time; Transport of a substance across the plasma membrane facilitated by a carrier molecule. Bind with specific substrates and carry them across membrane by changing conformation, can move larger molecules than channel proteins can. Slower rate than simple difusion, but still selective. carrier proteins specific yes do they get saturated yes how can the rate of transport via a specific carrier protein be increased only way rate of diffusion can increase is if there are more carrier proteins resting skeletal muscle increase glucose transport GLUT 4 proteins bind to membrane and recruits more carrier proteins to increase the rate of diffusion how exercising muscle increase glucose transport Glucose transport occurs primarily by facilitated diffusion, an energy independent process that uses a carrier protein for transport of a substrate across a membrane. The glucose transporter carrier proteins in mammalian tissues are a family of structurally related proteins that are expressed in a tissuespecific manner . GLUT4 is the major isoform present in both human and rat skeletal muscle, whereas the GLUT1 and GLUT5 isoforms are expressed at a much lower abundance . The major mediators of glucose transport activity in muscle are fiber contractions and insulin, although numerous other factors including catecholamines, hypoxia, growth factors, and corticosteroids can alter glucose transport. Glucose transport in skeletal muscle follows saturation kinetics, and most reports have shown that exercise and insulin increase glucose transport through an increase in the maximal velocity of transport (V max) without an appreciable change in the substrate concentration at which glucose transport is halfmaximal, orK m . This increase in transportV max may occur through an increase in the rate that each carrier protein transports glucose (transporter turnover number), an increase in the number of functional glucose transporter proteins present in the plasma membrane, or both. why is exercise an important treatment for diabetes physical work can stimulate muscle glucose uptake; exercise and insulin stimulate muscle glucose transport by distinct mechanisms 20. (From lecture and text): Know GLUT what is its function? For what type of membrane transport is it used … primary active transport? facilitated diffusion? or what? Distinguish between GLUT1, GLUT2, GLUT3, and GLUT4. GLUT a plasma membrane carrier that accomplishes passive facilitated diffusion of glucose across the plasma membrane Once GLUT facilitates entry of glucose into a cell down this nutrient’s concentration gradient, an enzyme within the cell immediately phosphorylates glucose to glucose6phosphate. what type of membrane transport is it used facilitated diffusion GLUT1 transports glucose across the bloodbrain barrier GLUT 2 transfers into the adjacent bloodstream the glucose that has entered the kidney and intestinal cells by means of the sodium and glucose cotransporter GLUT 3 is the main transporter of glucose into neurons. GLUT 4 The transporter responsible for glucose uptake by most body cells 21. Understand Na /K ATPase (pump) – Which ions are moved? How many at a time? In which compartment (ECF vs. ICF) is sodium concentration high? In which compartment is potassium concentration high? Given these answers, in + + which direction does the Na /K pump move each of these ions? What is the relationship between ATP and the phosphorylation/dephosphorylation of the pump, and how do phosphorylation and dephosphorylation relate to the function of the pump? Is this primary or secondary active transport? Which cells have the sodium/potassium pump? Primary Active Transport every cell has a Na+/K+ pump ATP is used by the carrier protein NA+/K+ 3NA+ out, 2 K+ in Na+ is high ECF K+ is high ICF Process 3 Na+ binds → ATP attaches → ATP is cut by the pump into ADP → leaves phosphate to the pump (phosphorylated) → causes pump to change shape → dumps 3 Na+ → picks up 2 K+ causes pump to dephosphorylate → changes shape and releases them → process repeats 22. Describe the glucose transport system (using the SGLT transporter) in the intestinal cell membrane (see Fig. 318, and see image on iLearn). Overall, how does the body transport glucose from the lumen into the blood? What transport proteins are in the luminal membrane? What transport proteins are in the basolateral membrane? What role do tight junctions play in how the luminal membrane is different from the basolateral membrane? Where in the overall process is energy (ATP) directly used? What aspect of the system requires an alternate form of energy, in the form of an ion concentration gradient? Making a connection … where in this glucose transport system is there a GLUT protein, and (from text p. 691) which specific GLUT protein is it? How does the body transport glucose from lumen into blood→ because of this Na+ concentration difference, more Na+ binds to the SGLT when it is exposed to the lumen than when it is exposed to the ICF. Binding of Na+ to this carrier increases the carrier’s affinity for glucose, so glucose binds to the SGLT when it is open to the lumen side where glucose concentration is low. When both Na+ and glucose are bound to it, the SGLT changes shape and opens to the inside of the cell. Both Na+ and glucose are released to the interior— Na+ because of the lower intracellular Na+ concentration and glucose because of the reduced affinity of the binding site on release of Na+. The movement of Na+ into the cell by this cotransport carrier is downhill because the intracellular Na+ concentration is low, but the movement of glucose is uphill because glucose becomes concentrated in the cell. The glucose carried across the luminal membrane into the cell by secondary active transport then moves passively out of the cell by facilitated diffusion across the basolateral membrane and into the blood. This facilitated diffusion, which moves glucose down its concentration gradient, is mediated by a passive GLUT identical to the one that transports glucose into other cells, but in intestinal and kidney cells it transports glucose out of the cell. The difference depends on the direction of the glucose concentration gradient. In the case of intestinal and kidney cells, the glucose concentration is higher inside the cells. What transport proteins are in the luminal membrane→ SGLT- cotransport carrier protein What transport proteins are in the basolateral membrane→ GLUT- glucose transporter What role do tight junctions play in how the luminal membrane is different from the basolateral membrane→ they are impermeable junctions that join the lateral edges of epithelial cells near their luminal borders, thus preventing movement of materials between the cells. Only regulated passage of materials can occur through these cells, which form highly selective barriers that separate two compartments of highly different chemical composition. Where in the overall process is energy (ATP) directly used→ ATP is required for the Na+/K+ pump to constantly pump 3 Na+ out, so that Na+ could move back in through the SGLT carrier protein What aspect of the system requires an alternate form of energy in the form of an ion concentration gradient→ SGLT requires Na+ to move down its ion concentration gradient from a high concentration in the lumen to low concentration in the ICF. Uses the energy of Na+ going downhill to make glucose go uphill. Where in this glucose transport system is there a GLUT protein→ the glucose carried across the luminal membrane into the cell by secondary active transport then moves passively out of the cell by facilitated diffusion across the basolateral membrane and into the blood. This facilitated diffusion, which moves glucose down its concentration gradient, is mediated by a passive GLUT identical to the one that transports glucose into other cells, but in intestinal and kidney cells it transports glucose out of the cell. Which specific GLUT protein is it→ GLUT 2 23. (From text): Understand transport by vesicular transport: exocytosis and endocytosis. Why are these transport processes needed? (In other words, why not just use a carrier protein?) Which type of transport is “secretion”? Which type of transport is followed by lysosomal action? Do the processes of exocytosis and endocytosis require energy? Also, compare and contrast: pinocytosis, receptor mediated endocytosis, and phagocytosis. To transport larger molecules exocytosis “out of”; the primary mechanism for accomplishing secretion; releases to the exterior of substances originating within the cell; fusion of a membraneenclosed intracellular vesicle with the plasma membrane followed by the opening of the vesicle and the emptying of its contents to the outside endocytosis internalization of extracellular material within a cell as a result of the plasma membrane forming a pouch that contains the extracellular material, then sealing at the surface of the pouch to form an endocytic vesicle Require energy; active method type of transport for secretion exocytosis, secretory vesicles transport followed by lysosomal action phagocytosis exocytosis and endocytosis require energy YES, they both require energy pinocytosis “cell drinking”; droplet of ECF is taken up non selectively; plasma membrane dips inward, forming a pouch that contains a bit of ECF, plasma membrane seals at the surface of the pouch trapping the contents in a small, intracellular endocytic vesicle or endosome. Dynamin, the protein responsible for pinching off an endocytic vesicle forms rings that wrap around and “wring the neck” of the pouch, severing the vesicle from the surface membrane. Pinocytosis provides a means to retrieve extra plasma membrane that has been added to the cell surface during exocytosis. receptormediated endocytosis a highly selective process that enables cells to import specific large molecules that it needs from its environment, it is triggered by the binding of a specific target molecule such as a protein to a surface membrane receptor specific for that molecule , the binding causes the plasma membrane at the site ot pocket inward and then seal at the surface trapping the bound molecule inside the cell. The pouch is formed by the linkage of clathrin molecules, which are membranedeforming coat proteins on the inner surface of the plasma membrane that bow inward, in contrast to the outwardcurving coat proteins that form buds. the resulting pouch is known as a coated pit because it is coated with clathrin. Cholesterol complexes, vitamin B12, the hormone insulin, and iron are examples of substances selectively tak
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