PHGY 170 Module 03: The Plasma Membrane and Mitochondria PDF

PHGY 170 oiw HUMAN CELL PHYSIOLOGY MODULE 03 THE PLASMA MEMBRANE AND MITOCHONDRIA Please note: This course was designed to be interacted and engaged with using the online modules. This Module Companion Guide is a resource created to complement the online slides. If there is a discrepancy between this guide and the online module, please refer to the module. How can you help protect the integrity and quality of your Queen’s University course? Do not distribute this Module Companion Guide to any students who are not enrolled in PHGY 170 as it is a direct violation of the Academic Integrity Policy of Queen’s University. Students found in violation can face sanctions. For more information, please visit https://www.queensu.ca/academic- calendar/health-sciences/bhsc/. MODULE 03 COMPANION GUIDE PHGY 170 TABLE OF CONTENTS INTRODUCTION..................................................................................................................................................... 6 Video: Introduction to Module 03................................................................................................................... 6 Module 03: Module Learning Outcomes........................................................................................................ 7 Module Assessments........................................................................................................................................ 7 Course Icons...................................................................................................................................................... 7 Module Outline.................................................................................................................................................. 8 SECTION 01: Introduction to the Plasma Membrane and Lipids..................................................................... 9 Introduction to The Plasma Membrane and Lipids...................................................................................... 9 Phospholipids.................................................................................................................................................... 9 The Six Major Types of Phospholipid Head Groups....................................................................................10 Phospholipids are Unique Building Blocks...................................................................................................12 Other Common Lipids in the Plasma Membrane........................................................................................12 Checkpoint Activity: Lipids in the Plasma Membrane Review....................................................................14 Section 01: Summary......................................................................................................................................14 SECTION 02: The Semipermeable Membrane.................................................................................................16 Introduction to The Semipermeable Membrane........................................................................................16 The Formation of the Plasma Membrane....................................................................................................16 Plasma Membrane Leaflets...........................................................................................................................18 Plasma Membrane Leaflets...........................................................................................................................19 Lipid Asymmetry..............................................................................................................................................21 Maintaining Lipid Asymmetry........................................................................................................................21 The Selective Permeability of the Plasma Membrane................................................................................23 Selective Permeability and Gradients...........................................................................................................24 Osmotic Gradients..........................................................................................................................................24 Aquaporins.......................................................................................................................................................25 Tonicity.............................................................................................................................................................25 Video: Osmosis and Tonicity..........................................................................................................................26 Video: Semipermeable Membrane Review..................................................................................................27 Checkpoint Activity: Selective Permeability..................................................................................................28 Checkpoint Activity: Tonicity..........................................................................................................................29 Section 02: Summary......................................................................................................................................30 SECTION 03: The Fluid-Mosaic Model...............................................................................................................31 HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 2 MODULE 03 COMPANION GUIDE PHGY 170 Introduction to The Fluid-Mosaic Model......................................................................................................31 The Original Fluid-Mosaic Model...................................................................................................................31 Revising the Fluid-Mosaic Model...................................................................................................................32 Factors Affecting Membrane Fluidity............................................................................................................33 Membrane Proteins........................................................................................................................................34 Checkpoint Question: Membrane Fluidity and Temperature....................................................................35 Checkpoint Question: Membrane Fluidity and Fatty Acids........................................................................35 Checkpoint Question: Membrane Fluidity and Cholesterol.......................................................................36 Section 03: Summary......................................................................................................................................36 SECTION 04: Membrane Transport...................................................................................................................37 Introduction to Membrane Transport..........................................................................................................37 Types of Membrane Transport......................................................................................................................37 Passive Transport: Channels and Carriers...................................................................................................37 Active Transport..............................................................................................................................................38 Active Transport: Symporters and Antiporters............................................................................................40 Activity: Cellular Transport Review................................................................................................................40 Checkpoint Question: Cellular Transport.....................................................................................................41 Section 04: Summary......................................................................................................................................41 SECTION 05: Cellular Metabolism and Mitochondria......................................................................................42 Introduction to Cellular Metabolism and Mitochondria.............................................................................42 Cellular Metabolism........................................................................................................................................42 Adenosine Triphosphate (ATP)......................................................................................................................42 Guanosine Triphosphate (GTP)......................................................................................................................43 Other High-Energy Molecules........................................................................................................................44 Power Plants of the Cell: Mitochondria........................................................................................................44 Mitochondrial Structure.................................................................................................................................45 Checkpoint: Cellular Metabolism..................................................................................................................46 Checkpoint Activity: Cellular Metabolism.....................................................................................................46 Section 05: Summary......................................................................................................................................47 SECTION 06: Metabolism (ATP Production)......................................................................................................48 Introduction to Cellular Respiration (ATP Production)................................................................................48 Energy Storage.................................................................................................................................................48 Storing ATP.......................................................................................................................................................49 HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 3 MODULE 03 COMPANION GUIDE PHGY 170 Sources of Glucose for Cellular Metabolism................................................................................................50 Getting Glucose into Cells..............................................................................................................................50 The 10 Steps of Glycolysis..............................................................................................................................51 Glycolysis in Three Stages..............................................................................................................................51 Stage 1 of Glucose Metabolism.................................................................................................................51 Stage 2 of Glucose Metabolism.................................................................................................................51 Stage 3 of Glucose Metabolism.................................................................................................................52 Summary of Glycolysis....................................................................................................................................52 The Fates of Pyruvate.....................................................................................................................................52 Anaerobic Metabolism....................................................................................................................................53 Question: Anaerobic Metabolism..................................................................................................................55 The Stages of Aerobic Respiration................................................................................................................55 Converting Pyruvate to Acetyl-CoA...............................................................................................................56 Krebs Cycle.......................................................................................................................................................57 Products of the Krebs Cycle...........................................................................................................................58 Oxidative Phosphorylation.............................................................................................................................59 The Electron Transport Chain (ETC)..............................................................................................................60 Complexes of the ETC......................................................................................................................................60 Video: Electron Transport Chain....................................................................................................................61 The Chemiosmotic Gradient..........................................................................................................................62 ATP Synthase....................................................................................................................................................63 Video: ATP Synthase........................................................................................................................................64 Aerobic Respiration: Counting ATP................................................................................................................65 Aerobic Respiration: Realistic Values............................................................................................................65 Aerobic Respiration Summary.......................................................................................................................66 Excess ATP........................................................................................................................................................68 Checkpoint Activity: Glucose Metabolism....................................................................................................69 Section 06: Summary......................................................................................................................................69 SECTION 07: Other Sources of Cellular Energy................................................................................................71 Introduction to Other Sources of Cellular Energy.......................................................................................71 Fat Metabolism................................................................................................................................................71 Transport of Fatty Acids.................................................................................................................................72 Beta Oxidation.................................................................................................................................................72 HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 4 MODULE 03 COMPANION GUIDE PHGY 170 Example: Beta Oxidation............................................................................................................................73 ATP Yield from Palmitic Acid......................................................................................................................73 Video: Fat Metabolism Summary..................................................................................................................74 Question: Beta Oxidation of a 10-Carbon Fatty Acid..................................................................................75 Question: Beta Oxidation Energy Yield of an 18-Carbon Fatty Acid..........................................................75 Protein Metabolism.........................................................................................................................................76 Destinations of Protein Metabolites.............................................................................................................76 Energy Preferences.........................................................................................................................................77 Energy Demands.............................................................................................................................................78 Section 07 Summary.......................................................................................................................................78 CONCLUSION.......................................................................................................................................................80 Module Conclusion.........................................................................................................................................80 Module 03: Complete!.....................................................................................................................................80 Module 03: Credits..........................................................................................................................................80 HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 5 MODULE 03 COMPANION GUIDE PHGY 170 INTRODUCTION Please see the online learning module for the full experience of interactions within this document. VIDEO: INTRODUCTION TO MODULE 0 3 This content was retrieved from Introduction Slide 2 of 6 of the online learning module. Welcome to Module 03, The Plasma Membrane and Mitochondria. In this module, you will explore the cell membrane and its transport mechanisms, as well as the mitochondrion and how it is essential in the metabolic processes of cellular respiration. Watch the video for an introduction to Module 03 from a content specialist. (01:24) Start of Video Transcript: Hi, I’m Dr.Chris Ward, one of your Physiology 170 content experts. In Module 03, we are exploring the plasma membrane and the mitochondria. The plasma membrane is probably one of the most important cellular structures. In this module, we will go over many functions of the plasma membrane. The most important function of the plasma membrane though, is that it allows a cell to regulate its internal environment which is essential for the overall function of the cell. This internal regulation is accomplished by the plasma membrane controlling how and when molecules and ions are able to move either in or out of the cell. In this module, we will take an in-depth look at all the structural components of the plasma membrane and the roles they contribute to its overall function. A focus on the functions of the plasma membrane where we learn all about the different types of membrane transport pathways. From simple diffusion of lipid soluble molecules to the energy-consuming process of active transport. These transport processes are essential to regulate their internal environment. Module 03 also takes an in-depth look at the mitochondria: the cellular organ responsible for the production of ATP, the primary energy for most cellular functions. We will examine how the mitochondria’s unique membrane structure allows the mitochondria to take some common molecules such as glucose and fatty acids and turn them, through the processes of glycolysis, Kreb’s cycle, and oxidative phosphorylation, into the energy necessary to power the cell. Thank you for watching this introduction to Module 03. End of Video Transcript. Page Link: https://player.vimeo.com/video/745483627 Reference: Chem Academy. (2015, Sept. 22). Chemical Symbols - Explained [Video]. Retrieved October, 2021 from: HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 6 MODULE 03 COMPANION GUIDE PHGY 170 https://www.youtube.com/watch?v=278r0UaP1Zs MODULE 03: MODULE LEARNING OUTCOMES This content was retrieved from Introduction Slide 3 of 6 of the online learning module. By the end of Module 03, you will be able to: 1. Explain the fluid-mosaic model and structures of the plasma membrane. 2. Discuss how membrane fluidity can be altered. 3. Describe different ways cells move materials from one side of the plasma membrane to the other. 4. Describe the membrane structure of mitochondria in order to explain the role of these membranes in ATP synthesis. 5. Compare the high-energy molecules found in cells to explain the cellular importance of ATP. 6. Outline the processes of glycolysis, Krebs Cycle, and oxidative phosphorylation in order to explain how ATP is produced in both aerobic and anaerobic conditions. 7. Compare how much energy can be made from proteins, carbohydrates, and fats. MODULE ASSESSMENTS This content was retrieved from Introduction Slide 4 of 6 of the online learning module. There are assessments associated with this module. At the end of this module, you will answer questions that will assess your understanding of the learning outcomes for the module. It is recommended that you read these learning outcomes and work to understand them as you progress through the content. For specific details about your module assessments, visit the assessment page in your online learning environment. Activities Throughout the Module: Note that responses to questions within the learning modules will not be graded unless otherwise specified. These are here to help you gauge your learning. However, your responses to these interactions are recorded in the module and viewable to the instructor(s). COURSE ICONS This content was retrieved from Introduction Slide 5 of 6 of the online learning module. As you navigate the course modules, you will come across these course icons. Continue to learn its purpose and function. Audio Clip: This icon indicates the presence of an audio clip on the slide from your instructor or other content experts. To play the audio clip, click the play button. Full transcripts and closed captions are available. References: This icon lives in the sidebar of the slides. Clicking it will reveal the references for content and/or images on the slide. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 7 MODULE 03 COMPANION GUIDE PHGY 170 Process: This icon lives in the sidebar of the slides. It will appear when there is a process or concept being described over multiple slides. Clicking it will reveal the full process or concept being described. MODULE OUTLINE This content was retrieved from Introduction Slide 6 of 6 of the online learning module. Section 01: Introduction to the Plasma Membrane and Lipids Section 02: The Semipermeable Membrane Section 03: The Fluid-Mosaic Model Section 04: Membrane Transport Section 05: Cellular Metabolism and Mitochondria Section 06: Metabolism (ATP Production) Section 07: Other Sources of Cellular Energy HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 8 MODULE 03 COMPANION GUIDE PHGY 170 SECTION 01: INTRODUCTION TO THE PLASMA MEMBRANE AND LIPIDS INTRODUCTION TO THE PLASMA MEMBRANE AND LIPIDS This content was retrieved from Section 01 Slide 2 of 8 of the online learning module. Recall from Module 01 that the plasma membrane is made of phospholipids. These phospholipids form a double layered sheet called a lipid bilayer, which is often referred to as being semi- permeable*. Specialized proteins can be found within the membrane that help to move molecules in and out of the cell, while certain kinds of molecules can pass right through the membrane. Hydrophobic molecules and small neutral molecules can freely diffuse through a membrane. Polar organic molecules, ions, and proteins cannot diffuse through a membrane. Some molecules can pass freely through the lipid bilayer whereas others cannot. Definition*: Semi-permeable: This means that some molecules may cross it while others cannot, which is how the membrane can control what comes in or out. PHOSPHOLIPIDS This content was retrieved from Section 01 Slide 3 of 8 of the online learning module. Phospholipids are a class of lipids found in the plasma membrane. Phospholipids, or phosphoglycerides, are composed of four major components: a head group, phosphate group, glycerol, and two fatty acid tails. Both the head group and the fatty acid tails can vary in structure, meaning that phospholipids are very diverse. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 9 MODULE 03 COMPANION GUIDE PHGY 170 Continue to learn about the four components of phospholipids. Head Group: The head group attaches to the phosphate group, and its chemical properties determine where the phospholipid ends up in the cell membrane. You will learn about the different head groups on the next slide. Phosphate Group: The hydrophilic charged component of the phospholipid. Glycerol: Glycerol is a three-carbon chain with three hydroxyl groups. It acts as the backbone of the phospholipid. Fatty Acid Tails: Two long hydrocarbon chains which can vary in composition and bond number (which alters rigidity). Thes attach to the glycerol backbone. THE SIX MAJOR TYPES OF PHOSPHOLIPID HEAD GROUPS This content was retrieved from Section 01 Slide 4 of 8 of the online learning module. Six major phospholipid head groups are found in eukaryotic cells. Recall that the chemical properties of these groups lead to their final destinations in cell membranes, and can give membranes some of their properties. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 10 MODULE 03 COMPANION GUIDE PHGY 170 It is not important to memorize full names or structures, but rather note their charges and letters (abbreviations). Continue to learn more about the six major head groups. Polar Phosphatidyl - inositol (PI) Phosphatidyl - glycerol (PG) Cardiolipin (CL) Charged Phosphatidyl- serine (PS) Phosphatidyl- ethanolamine (PE) Phosphatidyl- choline (PC) HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 11 MODULE 03 COMPANION GUIDE PHGY 170 PHOSPHOLIPIDS ARE UNIQUE BUILDING BLOCKS This content was retrieved from Section 01 Slide 5 of 8 of the online learning module. In previous modules, you learned that nucleotides and proteins are made of individual building blocks that form large complex polymers. Sugars exhibit this structural trend as well. In contrast, phospholipids are independent entities and do not form polymers. Rather, phospholipids are separate molecules that cluster together to form structures such as membranes. A phospholipids cluster forming a liposome. OTHER COMMON LIPIDS IN THE PLASMA MEMBRANE This content was retrieved from Section 01 Slide 6 of 8 of the online learning module. Other classes of lipids, such as cholesterol, glycolipids, and sphingomyelin (SM), are also found in the plasma membrane. Continue to learn about three important lipids in the plasma membrane. Cholesterol HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 12 MODULE 03 COMPANION GUIDE PHGY 170 Cholesterol is a major plasma membrane component in animal tissues. A key component of cholesterol is that it has a hydroxyl group on one of its rings. This ring will interact with the surface of the membrane, while the rest of the cholesterol molecule will interact with the lipid part of the membrane. Cholesterol in the lipid bilayer. Glycolipids Glycolipids are also common in membranes, and have a sugar carbohydrate group attached to the lipid, but no phosphate group. They are often involved in cell-to-cell signalling. The most common backbones for glycolipids are sphingosine and glycerol. Fatty acids attached directly to sugar moieties are another type of glycolipid. Glycolipids with a sphingosine and a glycerol backbone. Sphingomyelin Sphingomyelin (SM) is another common component in cell membranes. It resembles a phospholipid, but has a sphingosine backbone rather than glycerol. SM consists of a phosphocholine head group, sphingosine, and a fatty acid. Sphingolipids are common to the myelin sheaths found wrapping around the axons of nerve cells. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 13 MODULE 03 COMPANION GUIDE PHGY 170 Sphingomyelin. CHECKPOINT ACTIVITY: LIPIDS IN THE PLASMA MEMBRANE REVIEW This content was retrieved from Section 01 Slide 7 of 8 of the online learning module. Select the correct lipid type from the drop down menu to match with the proper characteristics. Options of Lipid Types: Sphingomyelin, Cholesterol, Phospholipids, Glycolipids Characteristics 1. Consists of a phosphocholine head group, phosphate group, sphingosine, and a fatty acid. 2. A four ring structure with a hydroxyl group that will be on the membrane surface. 3. Consists of a head group, a phosphate group, glycerol, and two fatty acid tails. 4. Have sugar groups attached to a sphingosine or glycerol backbone, but no phosphate group. Feedback: Correct answer: 1. Sphingomyelin 2. Cholesterol 3. Phospholipids 4. Glycolipids The lipids found in the plasma membrane serve important functions that vary on their specific characteristics. SECTION 01: SUMMARY This content was retrieved from Section 01 Slide 8 of 8 of the online learning module. In this section, you learned about the plasma membrane and the role it plays within cells. You briefly explored the types of molecules that can and cannot cross the plasma membrane. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 14 MODULE 03 COMPANION GUIDE PHGY 170 You learned that phospholipids are the main component of the plasma membrane and are composed of a head, phosphate group, glycerol, and a fatty acid tail. Finally, you were introduced to other lipids in the plasma membrane that play an important role in managing the integrity of the cell, including cholesterol, glycolipids, and sphingomyelins. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 15 MODULE 03 COMPANION GUIDE PHGY 170 SECTION 02: THE SEMIPERMEABLE MEMBRANE INTRODUCTION TO THE SEMIPERMEABLE MEMBRANE This content was retrieved from Section 02 Slide 2 of 17 of the online learning module. Recall from Section 01 that the cell membrane is a semipermeable lipid bilayer composed of phospholipids, which allows some molecules to freely cross while others require specialized proteins to move in and out of the cell. Phospholipids cluster spontaneously to maximize hydrophobic and hydrophilic interactions. This is important, because it means that membranes can reform easily and formation does not require high amounts of energy. Phospholipids aligning based on hydrophobic and hydrophilic interactions. THE FORMATION OF THE PLASMA MEMBRANE This content was retrieved from Section 02 Slide 3 of 17 of the online learning module. Phospholipids form four major types of phospholipid clusters: micelles, liposomes, monolayers, and bilayers. Continue to learn about the four types of phospholipid clusters. Micelles and Liposomes When surrounded by polar water (H2O), phospholipids will form either droplets with fatty acid tails in the center (micelles), or tight bilayers with a hollow middle (liposomes). HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 16 MODULE 03 COMPANION GUIDE PHGY 170 Monolayer At the boundary of water and atmosphere, phospholipids will form a single layer with the polar head groups pointed down into the polar H2O. Bilayer In cells, phospholipids form bilayers with the polar head groups pointed out towards the aqueous environment inside and outside of the cell. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 17 MODULE 03 COMPANION GUIDE PHGY 170 Reference: Plopper, G., & Ivankovic, D. B. (2020). Principles of Cell Biology (3rd ed.; pp.150). Jones & Bartlett Learning, LLC. Retrieved March 2022, from: http://ebookcentral.proquest.com/lib/queen- ebooks/detail.action?docID=6002586 PLASMA MEMBRANE LEAFLETS This content was retrieved from Section 02 Slide 4 of 17 of the online learning module. In cells, the phospholipid bilayers are called leaflets: The leaflet facing the cytoplasm is called the cytosolic face, or the cytoplasmic leaflet. The leaflet facing the exterior of the cell is the exoplasmic face, or the exoplasmic leaflet. Notice that for organelles with a single layer plasma membrane (i.e., endoplasmic reticulum, endosomes, and the lysosome), the “exoplasmic” face will now be the luminal face named for the lumen or interior space of the organelle. Two organelles have a double membrane. The nucleus has two layers, so the cytosolic face is on the exterior and interior, while the mitochondria requires the second membrane to form the intermembrane space which you will learn more about in the module. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 18 MODULE 03 COMPANION GUIDE PHGY 170 The positioning of exoplasmic and cytosolic faces of the membranous structures of a eukaryotic cell. Composition of the PLASMA MEMBRANE LEAFLETS This content was retrieved from Section 02 Slide 5 of 17 of the online learning module. Recall from Section 01 that different head groups of phospholipids possess different charges. The lipid asymmetry* of the plasma membrane is observed in composition of the exoplasmic and cytosolic leaflets. Relative lipid amounts differ between cell types, and even different organelles will have different ratios. Continue to explore the link between charge and location in the membrane. Plasma Membrane The amount of sphingomyelin (SM), phosphatidyl-choline (PC), phosphotidyl-serine (PS), and Phosphatidylinositol (PI) is variable between the exoplasmic and cytosolic leaflet. The cytosolic leaflet also contains phosphatidyl-ethanolamine (PE). HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 19 MODULE 03 COMPANION GUIDE PHGY 170 Red blood cell plasma membrane composition. Exoplasmic Leaflet Positively charged phospholipids like phosphatidyl-choline (PC) and sphingomyelin (SM) are the major components of the exoplasmic leaflet. This is also where glycolipids are located. Although phosphotidyl-serine (PS) is present, more is in the cytosolic leaflet. Percentage of total membrane lipid in the exoplasmic leaflet. Cytosolic Leaflet Neutral and negatively charged phospholipids tend to be in the cytosolic leaflet like phosphatidyl- serine (PS). Positively polar phosphatidyl-ethanolamine (PE) is also a major component in the cytosolic leaflet. Percentage of total membrane lipid in the cytosolic leaflet. Note: Note that cholesterol is found in both leaflets, although the amount is variable between the leaflets, membranes, and cell types. Cardiolipin is found in the inner membrane of mitochondria. This difference in leaflet composition reflects a property of plasma membranes termed lipid asymmetry. Definition*: Lipid Asymmetry: The irregular distribution of lipids. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 20 MODULE 03 COMPANION GUIDE PHGY 170 Reference: Adapted from: Lorent, J.H., Levental, K.R., Ganesan, L. et al. Plasma membranes are asymmetric in lipid unsaturation, packing and protein shape. Nat Chem Biol 16, 644–652 (2020). Retrieved March 2022, from: https://doi.org/10.1038/s41589-020-0529-6 LIPID ASYMMETRY This content was retrieved from Section 02 Slide 6 of 17 of the online learning module. Asymmetry is used by the cell to maintain function of the plasma membrane and the organelle membranes within the cell. If the lipid bilayer loses this organization, this serves as a danger signal that can trigger cell death. Glycolipids are found on the exoplasmic leaflet. You will learn more about cellular communication and cell death in Module 04. An example of asymmetry in the lipid bilayer. MAINTAINING LIPID ASYMMETRY This content was retrieved from Section 02 Slide 7 of 17 of the online learning module. Three types of transporters regulate the phospholipid composition of the plasma membrane. Continue to learn the functionality of lipid transporters. Floppases Selective floppases keep most PC, sphingomyelin, and cholesterol in the exoplasmic leaflet. Floppases like to flOp Out. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 21 MODULE 03 COMPANION GUIDE PHGY 170 Flippases Selective flippases keep most PS, PE, and PI in the cytosolic leaflet. Flippases like to flIp In. Scramblases Scramblases briefly disrupt membrane asymmetry by randomizing phospholipids. Scramblases scramble up the asymmetry. Reference: HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 22 MODULE 03 COMPANION GUIDE PHGY 170 Plopper, G., & Ivankovic, D. B. (2020). Principles of Cell Biology (3rd ed.; pp.179). Jones & Bartlett Learning, LLC. Retrieved March 2022, from: http://ebookcentral.proquest.com/lib/queen- ebooks/detail.action?docID=6002586 THE SELECTIVE PERMEABILITY OF THE PLASMA MEMBRANE This content was retrieved from Section 02 Slide 8 of 17 of the online learning module. The plasma membrane is said to be selectively permeable, which means that some molecules can diffuse freely into and out of the cell, while others cannot. Continue to review what type of molecules can and can’t pass through the membrane. Can Diffuse Freely Small uncharged and hydrophobic molecules can pass through or diffuse freely. This includes gases like oxygen (O2), nitric oxide (NO), carbon dioxide (CO2) that diffuse freely through the membrane. Cannot Diffuse Freely Hydrophilic compounds and large molecules cannot pass through. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 23 MODULE 03 COMPANION GUIDE PHGY 170 SELECTIVE PERMEABILITY AND GRADIENTS This content was retrieved from Section 02 Slide 9 of 17 of the online learning module. Diffusion of small, hydrophobic molecules can only occur through the plasma membrane if there is a sufficient gradient moving them in this direction. A gradient is defined as an increase or decrease of the magnitude of a property (such as molecule concentration, in the case of concentration gradients) from one point to another. When able, molecules naturally move from areas of high concentration to areas of low concentration. On the next slides, you will learn about two kinds of gradients: osmotic gradients and concentration gradients. OSMOTIC GRADIENTS This content was retrieved from Section 02 Slide 10 of 17 of the online learning module. When a membrane is semi-permeable to a certain molecule and there is a difference in the concentration of the molecule between one side of the membrane and the other, there is a concentration gradient. This leads to osmotic pressure, a specific type of gradient that determines water movement, called an osmotic gradient. This describes how water moves across a membrane to areas of higher solute concentration. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 24 MODULE 03 COMPANION GUIDE PHGY 170 AQUAPORINS This content was retrieved from Section 02 Slide 11 of 17 of the online learning module. Water can move freely through the plasma membrane, but this is a slow process. The cell needs to maintain water balance on each side of the membrane. To do this, the cell uses passive transport channels called aquaporins. Aquaporins are channels that have a hydrophilic interior to allow water to move through the plasma membrane. TONICITY This content was retrieved from Section 02 Slide 12 of 17 of the online learning module. Osmotic pressure is measured in a cell by a property called tonicity. Tonicity describes the relative concentrations of solutes on either side of a cell’s membrane. There are three classifications of tonicity. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 25 MODULE 03 COMPANION GUIDE PHGY 170 Continue to learn about the three types of tonicity. Hypertonicity A hypertonic solution has greater amounts of solute outside of the cell than inside, causing water to flow out of the cell. This can cause the cell to lose volume. Isotonicity An isotonic solution has equal amounts of solute inside and outside of the cell. This is the ideal state for a cell. Hypotonicity A hypotonic solution has lower amounts of solute outside the cell than inside, causing water to flow in. This makes the cell swell, and can result in cell lysis. VIDEO: OSMOSIS AND TONICITY This content was retrieved from Section 02 Slide 13 of 17 of the online learning module. You will now watch a video that reviews the concepts of osmosis and tonicity, and explores their applications in the cell. Watch the video for an overview of osmosis and tonicity. (02:24) As you watch, think about the applications that these properties would have in the body, and how they could contribute to etiologies of diseases such as diabetes. Start of Video Transcript: Before we take a look at how osmosis and tonicity affect a cell, let’s review what each of these terms means. Osmosis represents the diffusion of water across a semipermeable membrane. The term tonicity refers to the relative solute concentration of two environments separated by a semipermeable membrane. In other words, by comparing the tonicity of the solution, you can determine the direction in which osmosis will occur. To demonstrate how tonicity affects a cell, let’s place some red blood cells into a beaker containing pure water. In this case, the solute concentration is greater inside the cells, than in the surrounding water. In other words, the contents of the cells are hypertonic in relation to the hypotonic contents of the beaker. Because of this, osmotic pressure results in the diffusion of water across the membrane and into the cells. Over time, if enough water enters the cells, the cell membranes may burst. This is called lysis. Now let’s place the red blood cells in a beaker containing a solution of salt, such as sodium chloride. Since the contents of the beaker are hypertonic in relation to the interior of the cell, the water within the cell will diffuse across the membrane and into the contents of the beaker. This causes crenation or shrinking of the cells. If the red blood cells are placed in a beaker whose contents match the tonicity within the cells, then there is no net gain or loss of water. The environments within the beaker and inside the cells are said to be isotonic, or the same. An important thing to remember, is that osmotic pressure always causes water to move from a hypotonic environment toward a hypertonic environment. In other words, water moves toward areas of high HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 26 MODULE 03 COMPANION GUIDE PHGY 170 salt or sugar concentrations. This simple process is used to drive the operation of our kidneys and explains some of the physiological consequences of diseases such as diabetes. End of Video Transcript. Page Link: https://www.youtube.com/embed/Y_w07A7chnk Reference: RicochetScience. (2013, Sept 13). Osmosis and Tonicity. Retrieved March 2022, from: https://www.youtube.com/watch?v=Y_w07A7chnk VIDEO: SEMIPERMEABLE MEMBRANE REVIEW This content was retrieved from Section 02 Slide 14 of 17 of the online learning module. You will now watch a video to solidify your understanding of how substances move across the semipermeable membrane. Watch the video for an overview of the semipermeable plasma membrane. (10:50) As you watch, think about some of the examples you learned about in this section and how they would apply. Start of VideoTranscript: Substances move into and out of a cell through several different processes, called membrane transport. There are two main processes, passive transport processes and active transport processes. The main difference between the two is that passive processes do not require energy expenditure and active processes do require the cells to expend energy. Let’s start by looking at the passive processes, which include simple diffusion, facilitated diffusion, and osmosis. Diffusion is the movement of a substance from where it has a high concentration to where it has a low concentration, or the tendency of a substance to spread out evenly over a given space. For instance, when a sugar cube is dissolved in water, over time the cube will dissolve and eventually spread out evenly in the water, until it reaches equilibrium. Diffusion occurs down a concentration gradient, which is a difference in concentration of a substance between two areas. So, the sugar molecules will move from an area of high concentration to an area of low concentration. Cellular diffusion is when diffusion of a solute, which is a dissolved substance, occurs across the plasma membrane from an area of high concentration to an area of low concentration. This is dependent on the concentration of a substance in the interstitial fluid outside the cell, and the cytosol inside the cell. This can occur through simple diffusion or facilitated diffusion. Simple diffusion occurs with solutes that are small and non-polar. By being non polar they can move in between phospholipid molecules that form the plasma membrane because the interior region of the membrane is non-polar. Some of the materials that move by simple diffusion include the gases oxygen and carbon dioxide, and small fatty acids. So, if there is a higher concentration of oxygen O2 molecules outside of a cell, they can move down the concentration gradient, across the membrane without assistance, and into HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 27 MODULE 03 COMPANION GUIDE PHGY 170 the cell, as long as the concentration gradient exists. And if there is a higher concentration of carbon dioxide CO2 molecules inside a cell, they can move across the membrane without assistance, out of the cell into the interstitial fluid. So, again, simple diffusion is when non polar molecules pass directly through a membrane. The second type of diffusion is facilitated diffusion. This applies to solutes that are small and either charged or polar. Because these solutes are polar, the non-polar phospholipid bilayer blocks them from passing through the membrane and into or out of the cell by simple diffusion. However, they can pass into and out of the cell with the assistance of plasma membrane proteins through a process called facilitated diffusion. There are two types of facilitated diffusion, channel mediated diffusion and carrier mediated diffusion. The difference between the two is the type of transport protein used to move the substance across the membrane. Channel mediated diffusion is when an ion, which is a charged particle where its total number of electrons does not equal its total number of protons, giving it a positive or negative charge, moves across the membrane through a water-filled protein channel. Each protein channel is typically specific for one type of ion, and there are two types of channels, a leak channel, which is continuously open, and a gated channel, which only opens due to a stimulus, and only stays open for a fraction of a second. So, for a sodium positive ion, it can pass through a sodium positive leak channel continuously and a gated sodium positive channel will only open due to a stimulus to allow the ion to pass through into the cell. Carrier mediated diffusion involves the movement of polar molecules such as simple sugars or simple carbohydrates and amino acids across the membrane. This is accomplished by a carrier protein, which actually changes shape in the process. For instance, glucose binds to a carrier protein, which changes shape and moves the glucose molecule to the other side of the membrane. Now, for osmosis. Osmosis is the passive movement of water through a selectively permeable membrane. This occurs when there is a difference in concentration of water on either side of the membrane. This can happen in one of two ways, water can slip between the phospholipid molecules that make up the plasma membrane, or through integral protein water channels that are called aquaporins. The plasma membrane is not permeable to most solutes, such as charged, polar and large substances, so for example, one side of the membrane, the cytosol or interstitial fluid, can have more solutes than the other side. Let's say the interstitial fluid has 3 percent solutes and 97 percent water, and the cytosol side has 1 percent solutes and 99 percent water. In this example water will move down its concentration gradient from the 99 percent cytosol side to the 97 percent interstitial side to achieve equilibrium. End of Video Transcript. You will learn more about active and passive transport in Section 04 Page Link: https://www.youtube.com/embed/J5pWH1r3pgU?start=42&end=349 Reference: Whats Up Dude. (2018, January 15). Cell Membrane Transport—Transport Across A Membrane—How Do Things Move Across A Cell Membrane. https://www.youtube.com/watch?v=J5pWH1r3pgU CHECKPOINT ACTIVITY: SELECTIVE PERMEABILITY This content was retrieved from Section 02 Slide 15 of 17 of the online learning module. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 28 MODULE 03 COMPANION GUIDE PHGY 170 Complete the activity by selecting whether each substance can or cannot freely pass through the plasma membrane. Options: Can pass, Cannot pass Substance 1. Small, uncharged molecules 2. Hydrophilic compounds 3. Large molecules 4. Gases Feedback: Correct answers: 1. Can pass 2. Cannot pass 3. Cannot pass 4. Can pass Small uncharged molecules and gases such as oxygen, nitric oxide, and carbon dioxide can pass freely through the plasma membrane, while hydrophilic compounds and large molecules cannot and require specialized proteins. CHECKPOINT ACTIVITY: TONICITY This content was retrieved from Section 02 Slide 16 of 17 of the online learning module. Select the correct term from the drop down menu to match the definition. List of terms: Hypotonic, Isotonic, Hypertonic HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 29 MODULE 03 COMPANION GUIDE PHGY 170 Definition: 1. A solution that has greater amounts of solute outside of the cell than inside, causing water to flow out of the cell. 2. A solution that has equal amounts of solute inside and outside of the cell. 3. A solution that has lower amounts of solute outside the cell than inside, causing water to flow in. Feedback: Correct answer: 1. Hypertonic 2. Isotonic 3. Hypotonic SECTION 02: SUMMARY This content was retrieved from Section 02 Slide 17 of 17 of the online learning module. In this section, you learned more about the semipermeable nature of the plasma membrane, meaning it allows some molecules to pass through and limits others. You learned about the formation of the plasma membrane through four types of phospholipid clusters - micelles, liposomes, monolayers, and lipid bilayers. The plasma membrane has a cytoplasmic and exoplasmic leaflet, and each of these leaflets is composed of different ratios of phospholipid head groups. This asymmetry between the cytoplasmic and exoplasmic leaflets is important for maintaining cell function. Lipid asymmetry is maintained by transporters, including floppases, flippases, and scramblases. Finally, you learned about molecules that can freely pass through the plasma membrane (small uncharged molecules) and those that cannot (hydrophilic compounds and large molecules). Aquaporins allow water to move down its osmotic gradient. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 30 MODULE 03 COMPANION GUIDE PHGY 170 SECTION 03: THE FLUID-MOSAIC MODEL INTRODUCTION TO THE FLUID -MOSAIC MODEL This content was retrieved from Section 03 Slide 2 of 10 of the online learning module. In Section 01 of this module, you learned that lipids are not the only components in the cell membrane. In addition to phospholipids, glycolipids, cholesterols, and sphingomyelins, other major components of the membrane include proteins and sugars. This contributes to a changing “mosaic” of components in the membrane, a concept that is described in the prevailing theory of cell membranes: the fluid-mosaic model. In Module 02, you learned that once proteins are translated, they can then be transported through the endomembrane network to their final destinations, including the plasma membrane. This is the process by which the membrane proteins reach the membrane “mosaic”. THE ORIGINAL FLUID-MOSAIC MODEL This content was retrieved from Section 03 Slide 3 of 10 of the online learning module. The fluid-mosaic model states that membranes can be considered a two-dimensional liquid where all lipid and protein molecules can diffuse more or less easily. The “mosaic” part of the fluid-mosaic model is based on the fact that there are multiple components to the membranes, rather than just the phospholipid bilayer. The “fluid” part of the model refers, in part, to the lipids and other molecules being able to move freely in the two-dimensional plane of the membrane, and to do so rapidly. A single phospholipid can move from one end of a eukaryotic cell to the other in a few seconds. Continue to learn about the original fluid-mosaic model. Original Model The original fluid-mosaic model assumed that the phospholipid bilayer was homogenous and of even thickness. The thickness of the phospholipid bilayer is now known to be quite variable. Reference: HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 31 MODULE 03 COMPANION GUIDE PHGY 170 Plopper, G., & Ivankovic, D. B. (2020). Principles of Cell Biology (3rd ed.; pp.153). Jones & Bartlett Learning, LLC. Retrieved March 2022, from: http://ebookcentral.proquest.com/lib/queen- ebooks/detail.action?docID=6002586 REVISING THE FLUID -MOSAIC MODEL This content was retrieved from Section 03 Slide 4 of 10 of the online learning module. Elaborating on the concepts described by the original model, a revised fluid-mosaic model was created 30 years later. Continue to learn about two key elements of the revised fluid-mosaic model. Membrane Constituents Membrane constituents such as phospholipids, cholesterol, and proteins can join together to form complexes in the membrane. Hydrophilic Groups The hydrophilic head groups of phospholipids can interact with hydrophilic portions of membrane proteins. A cluster of membrane proteins, phospholipids and other membrane constituents is called a lipid raft*. Definition*: Lipid Raft: A lipid raft is a cluster of membrane proteins, phospholipids, and other membrane constituents forming distinct patches that are chemically and physically distinct from the surrounding membrane. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 32 MODULE 03 COMPANION GUIDE PHGY 170 Reference: Plopper, G., & Ivankovic, D. B. (2020). Principles of Cell Biology (3rd ed.; pp.153). Jones & Bartlett Learning, LLC. Retrieved March 2022, from: http://ebookcentral.proquest.com/lib/queen- ebooks/detail.action?docID=6002586 FACTORS AFFECTING MEMBRANE FLUIDITY This content was retrieved from Section 03 Slide 5 of 10 of the online learning module. Several factors can affect the nature of the plasma membrane, especially its fluidity. Continue to explore the factors affecting membrane fluidity. Temperature As temperature increases, the motion in the membrane increases, making it more flexible. Cooler temperatures will cause the membrane to become more rigid. A graph showing the relationship between temperature and membrane flexibility. Lipid Content The length of lipid chains influences the rate of movement of the plasma membrane. Shorter lipids (less than 16 carbons) move much more compared to longer chains. Further, whether the lipids are saturated or unsaturated will influence the movement across the membrane. Unsaturated lipids have kinks in the fatty acid tail of the phospholipid, which cause more space in the plasma membrane. This leads to more movement, since the phospholipids cannot interact with each other as closely as with saturated lipids which don’t have these kinks. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 33 MODULE 03 COMPANION GUIDE PHGY 170 Cholesterol Content Cholesterol is rigid, bulky, and hydrophobic, and thus, acts as a spacer in lower concentrations making a membrane more fluid. In higher concentrations (50% or higher), it will make the membrane more rigid and reduce membrane fluidity. Protein Content Proteins tend to be in complexes with each other and other parts of the cell membrane, sometimes forming “rafts.” Some membranes in the cell are very protein rich, and therefore have less movement in the membrane (i.e., the membrane is stiffer). There are several different structural classes of proteins in the membrane (shown in the figure). Additional proteins or sugars can also associate with each other. MEMBRANE PROTEINS This content was retrieved from Section 03 Slide 6 of 10 of the online learning module. Recall what you learned about protein content in the plasma membrane. There are many different types of proteins that associate with the membrane. Some you have already seen, some you will investigate further in later modules. Continue to learn about different kinds of membrane proteins. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 34 MODULE 03 COMPANION GUIDE PHGY 170 Signalling Molecules Signalling molecules include proteins involved in cell communication. You will learn about signalling molecules in Module 04. Integrins Integrins are membrane-bound proteins that facilitate cell adhesion and cytoskeleton movement. You will learn about integrins in Module 05. Receptors Receptors on the surface of cells can facilitate endo- or exocytosis or be used in cell signalling. You learned about some receptors in Module 02 and will learn more about receptors in Module 04. Channels and Transporers You will learn about channels and transporters moving material across the membrane in Section 04 of this module. Anchors and Junctions These proteins help cells move and attach to other cells and the extracellular matrix. You will learn about anchors and junctions in Module 05 and Module 06 respectively. CHECKPOINT QUESTION: MEMBRANE FLUIDITY AND TEMPERATURE This content was retrieved from Section 03 Slide 7 of 10 of the online learning module. Answer the question using what you have learned about factors that affect membrane fluidity. Question 1 of 3: High temperatures increase membrane fluidity. a) True b) False Feedback: Correct answer: a High temperatures increase membrane fluidity and low temperatures decrease membrane fluidity. The membrane is more flexible at higher temperatures and more rigid at lower temperatures. CHECKPOINT QUESTION: MEMBRANE FLUIDITY AND FATTY ACIDS This content was retrieved from Section 03 Slide 8 of 10 of the online learning module. Answer the question using what you have learned about factors that affect membrane fluidity. Question 2 of 3: How do unsaturated and saturated fatty acids affect the plasma membrane’s fluidity? HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 35 MODULE 03 COMPANION GUIDE PHGY 170 a) Unsaturated fatty acids decrease membrane fluidity and saturated fatty acids increase membrane fluidity. b) Unsaturated fatty acids increase membrane fluidity and saturated fatty acids decrease membrane fluidity. c) All fatty acids increase membrane fluidity. d) All fatty acids decrease membrane fluidity. Feedback: Correct answer: b Unsaturated fatty acids increase membrane fluidity and saturated fatty acids decrease membrane fluidity. The kinks in unsaturated fatty acids create more space in the membrane which increases fluidity. CHECKPOINT QUESTION: MEMBRANE FLUIDITY AND CHOLESTEROL This content was retrieved from Section 03 Slide 9 of 10 of the online learning module. Answer the question using what you have learned about factors that affect membrane fluidity. Question 3 of 3: Low concentrations of cholesterol decrease membrane fluidity. a) True b) False Feedback: Correct answer: b High concentrations of cholesterol decrease membrane fluidity and low concentrations of cholesterol increase membrane fluidity. Cholesterol acts as a spacer in low concentrations which increases the flexibility of the membrane, but in high concentrations it adds to the rigidity of the membrane. SECTION 03: SUMMARY This content was retrieved from Section 03 Slide 10 of 10 of the online learning module. In this section, you were introduced to the concept of the fluid-mosaic model of the plasma membrane. The original fluid-mosaic model assumed the plasma membrane was homogenous and of even thickness. However, thickness of the phospholipid bilayer is now known to be quite variable. The characteristics of the plasma membrane (particularly its fluidity) is influenced by temperature, lipid content, cholesterol content, and protein content. Various proteins can be found in the plasma membrane, including signalling molecules, integrins, receptors, channels and transporters, anchors and junctions. You will learn about channels and transporters in Section 04 of this module. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 36 MODULE 03 COMPANION GUIDE PHGY 170 SECTION 04: MEMBRANE TRANSPORT INTRODUCTION TO MEMBRANE TRANSPORT This content was retrieved from Section 04 Slide 2 of 9 of the online learning module. As discussed in Section 02, the plasma membrane is selectively permeable. But the cell also needs to be able to move specific cargo across the membrane, even if it cannot diffuse across the membrane. This requires intermembrane proteins like transporters and channels. These can allow cells to alter gradients and move cargo into or out of the cell. TYPES OF MEMBRANE TRANSPORT This content was retrieved from Section 04 Slide 3 of 9 of the online learning module. There are two categories of membrane transport: passive and active. Both are mediated by channel or carrier proteins. You will learn more about both types of transport throughout the rest of this section. Reference: Ancinec, DA. (2016). What do active transport require that osmosis does not? [Digital Image]. Biology 107 Resources. Retrieved March 2022, from: http://homework.sdmesa.edu/dancinec/sectional- review/chemistry/ans-11.htm PASSIVE TRANSPORT: CHANNELS AND CARRIERS This content was retrieved from Section 04 Slide 4 of 9 of the online learning module. Passive transport is the movement of molecules across a membrane down their concentration gradient, which does not require energy. This can include simple diffusion (like gasses) or facilitated diffusion described below. The two types you will focus on are: HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 37 MODULE 03 COMPANION GUIDE PHGY 170 Channel-mediated transport Carrier-mediated transport Continue to compare channel and carrier proteins. Channel Proteins Channel proteins form pores allowing water and small charged molecules, such as ions, to pass through the hydrophobic membrane. Some channels act as gates that open and close when turned on or off by a signal. Aquaporins are an example. Carrier Proteins Carrier proteins undergo a conformational change to allow their cargo to pass from one side of the membrane to the other. Some carriers are considered active transporters if this conformational change requires energy. Reference: Plopper, G., & Ivankovic, D. B. (2020). Principles of Cell Biology (3rd ed.; pp.167). Jones & Bartlett Learning, LLC. Retrieved March 2022, from: http://ebookcentral.proquest.com/lib/queen- ebooks/detail.action?docID=6002586 ACTIVE TRANSPORT This content was retrieved from Section 04 Slide 5 of 9 of the online learning module. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 38 MODULE 03 COMPANION GUIDE PHGY 170 Active transport requires energy to move molecules across the membrane against their concentration gradient. Pump proteins are common active transporters, and are modified carrier proteins that use energy to build gradients. Adenosine triphosphate (ATP) is typically the type of energy that is used. You will learn more about ATP in the next section. Active transporters can be direct or indirect. Continue to learn more about direct and indirect active transporters. Direct The Na+ /K+ antiporter pump is an example of a direct active transporter. The pump directly uses ATP to create Na+ and K+ gradients. The pump moves molecules across the membrane against a gradient. Indirect The Na+/glucose symporter is an example of an indirect active transporter. It uses the Na+ to create a glucose gradient (no ATP required). The pump does not directly use ATP, rather it uses the Na+ gradient established by a direct active transporter. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 39 MODULE 03 COMPANION GUIDE PHGY 170 Reference: Plopper, G., & Ivankovic, D. B. (2020). Principles of Cell Biology (3rd ed.; pp.170). Jones & Bartlett Learning, LLC. Retrieved March 2022, from: http://ebookcentral.proquest.com/lib/queen- ebooks/detail.action?docID=6002586 ACTIVE TRANSPORT: SYMPORTERS AND ANTIPORTERS This content was retrieved from Section 04 Slide 6 of 9 of the online learning module. Active transporters can also be classified as symporters or antiporters. Continue to distinguish between symporters and antiporters. Symporters Symporters will move molecules in the same direction. Antiporters Antiporters will move one molecule in and the other molecule out. Reference: Plopper, G., & Ivankovic, D. B. (2020). Principles of Cell Biology (3rd ed.; pp.168). Jones & Bartlett Learning, LLC. Retrieved March 2022, from: http://ebookcentral.proquest.com/lib/queen- ebooks/detail.action?docID=6002586 ACTIVITY: CELLULAR TRANSPORT REVIEW This content was retrieved from Section 04 Slide 7 of 9 of the online learning module. The interactive cell membrane is a great resource to explore how the semipermeable membrane can move molecules from one side to the other. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 40 MODULE 03 COMPANION GUIDE PHGY 170 For your interest, continue to explore the interactive cell membrane. Interactive Cell Membrane Page Link: https://pbslm-contrib.s3.amazonaws.com/WGBH/conv19/tdc02-int-membraneweb/index.html CHECKPOINT QUESTION: CELLULAR TRANSPORT This content was retrieved from Section 04 Slide 8 of 9 of the online learning module. Answer the question using what you have learned about cellular transport. Question 1 of 1: Which molecules pass through the plasma membrane using passive transport. Select all that apply. a) Oxygen b) Carbon dioxide c) Glucose d) Potassium e) Sodium f) Water Feedback: Correct answer(s): a, b, f Oxygen, carbon dioxide, and water passively cross the plasma membrane according to their concentration gradient. Although glucose is transported via facilitated diffusion, it uses indirect active transport with sodium which requires energy. It still goes down its concentration gradient with sodium. Sodium and potassium are transported against their concentration gradient, a process which uses ATP, so they use active transport. SECTION 04: SUMMARY This content was retrieved from Section 04 Slide 9 of 9 of the online learning module. In this section, you learned about the ways that cells can get cargo into the cell, when it’s not able to freely diffuse across the plasma membrane. Membrane transport can be passive or active. Passive transport is the movement of molecules across a membrane down their concentration gradients, which does not require energy, and includes channel and carrier proteins. Active transport requires energy to move molecules across the membrane against their concentration gradients. Active transport includes direct and indirect transport, and you learned that these transporters can be further classified as symporters and antiporters depending on the direction in which they move molecules. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 41 MODULE 03 COMPANION GUIDE PHGY 170 SECTION 05: CELLULAR METABOLISM AND MITOCHONDRIA INTRODUCTION TO CELLULAR METABOLISM AND MITOCHONDRIA This content was retrieved from Section 05 Slide 2 of 11 of the online learning module. So far in this course, you have focused on the components of the cell and their primary functions. An important aspect that you have not yet learned about is the energy required to fuel cellular processes. Life requires quite a lot of energy! You use energy when you move your body, process oxygen, pump your blood, and even when you think. On a smaller scale, your cells use energy in cell division, production of proteins, processing waste, communication with other cells, movement of molecules across membranes, and to power many other cellular processes. Throughout the rest of this module, you will learn about what the cell uses for fuel and how the cell uses this fuel to produce energy. In this section, you will be introduced to mitochondria, the powerhouse of the cell and the location of many key parts of cellular metabolism (e.g., glycolysis and fatty acid synthesis in the cytosol which you will learn about in Sections 06 and 07, respectively). CELLULAR METABOLISM This content was retrieved from Section 05 Slide 3 of 11 of the online learning module. Cellular metabolism is the summation of all of the different reactions that take place in a cell. In general, these biochemical reactions can be classified as either catabolism or anabolism. Continue to learn about these biochemical reactions. Catabolism Catabolism is the breakdown of cellular macromolecules. With respect to cellular energy, catabolism releases the energy stored within macromolecules so that it can be transferred to other molecules. This energy is ultimately stored as ATP and is the cell’s primary source of energy. Anabolism Anabolism is the production of cellular macromolecules. Anabolic reactions consume the ATP produced by catabolism, as small molecules are built into the macromolecules needed by the cell. ADENOSINE TRIPHOSPHATE ( ATP) This content was retrieved from Section 05 Slide 4 of 11 of the online learning module. Adenosine triphosphate (ATP) is the primary energy source for cellular processes. ATP is composed of an adenine molecule, a ribose sugar, and a chain of three phosphates. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 42 MODULE 03 COMPANION GUIDE PHGY 170 These phosphates are important as a lot of energy is stored in the bond between the second and third phosphates. When the third phosphate is removed, adenosine diphosphate (ADP) is formed and energy is released, which can be used in cellular processes. Continue to learn about an ATP molecule and an ADP and phosphate created when energy is released. An ATP Molecule An ADP Molecule + Phosphate GUANOSINE TRIPHOSPHATE ( GTP) This content was retrieved from Section 05 Slide 5 of 11 of the online learning module. Another molecule you may come across when researching cellular metabolism is guanosine triphosphate (GTP). GTP is identical to ATP, except the adenosine is replaced with guanosine. GTP is another primary cellular energy source and, for the purpose of this course, can be considered the same as ATP. It provides the energy for forming the peptide bonds in protein translation, for example, in Module 01. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 43 MODULE 03 COMPANION GUIDE PHGY 170 OTHER HIGH-ENERGY MOLECULES This content was retrieved from Section 05 Slide 6 of 11 of the online learning module. In addition to ATP and GTP, there are two other cellular energy molecules that will be discussed in this module: NAD+ and FAD. In contrast to energy being stored in phosphate bonds, these molecules carry electrons, which is how they store energy. Continue to learn about these high-energy molecules. NAD+ Nicotinamide adenine dinucleotide, or NAD+, is converted to a high energy form by the addition of an hydrogen (H+) ion and two electrons, producing NADH. FAD FAD is converted to a high energy form by the addition of two H+ ions and two electrons, producing FA DH2. POWER PLANTS OF THE CELL: MITOCHONDRIA This content was retrieved from Section 05 Slide 7 of 11 of the online learning module. Since ATP is so essential to many cellular functions, cells need a reliable way to produce it. The solution: mitochondria. As introduced in Module 01, the mitochondria are frequently called the power plants of the cell. Mitochondria are organelles that take large macromolecules and break them down to produce the energy, in the form of ATP, that cells need. A typical animal cell has 1000 to 2000 mitochondria in order to keep up with energy needs. However, cells with higher energy needs, such as muscle cells, can have many more mitochondria. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 44 MODULE 03 COMPANION GUIDE PHGY 170 Note the multiple mitochondria within the cytosol of a cell. Reference: A New-and Reversible-Cause of Aging. By David Cameron. December 19, 2013. Retrieved March 2022, from: https://hms.harvard.edu/news/new-reversible-cause-aging MITOCHONDRIAL STRUCTURE This content was retrieved from Section 05 Slide 8 of 11 of the online learning module. The structure of mitochondria is critical for their function. Mitochondria are double membraned organelles. Continue to learn more about the matrix and cristae. Cristae The inner membrane appears to be folded in on itself to form structures that are called cristae. This is where enzymes convert high-energy compounds into ATP. Matrix The inside of the mitochondria is called the matrix and this is where macromolecules are converted into small, high-energy compounds such as NADH. These compounds are then converted into ATP within the cristae. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 45 MODULE 03 COMPANION GUIDE PHGY 170 Note: Mitochondria even contain their own DNA to help them produce some of the proteins necessary for ATP production. CHECKPOINT: CELLULAR METABOLISM This content was retrieved from Section 05 Slide 9 of 11 of the online learning module. Continue to review what you have learned about anabolism and catabolism. Anabolism Catabolism Energy Requires energy Releases energy Reactions Production of macromolecules Breakdown of macromolecules Examples Of End Products Proteins, complex sugars, fatty ATP, amino acids, waste acids products CHECKPOINT ACTIVITY: CELLULAR METABOLISM This content was retrieved from Section 05 Slide 10 of 11 of the online learning module. Select the correct term from the drop down menu to match the definition. List of terms: NAD+, Cristae, ATP, Anabolism, Matrix, Catabolism Definitions: 1. The breakdown of cellular macromolecules. 2. Where enzymes convert food molecules into small, high-energy compounds. 3. The production of cellular macromolecules. 4. The primary energy source in cellular processes. 5. Where high-energy compounds are converted into ATP. 6. Changed to its high energy form by the addition of an H+ ion and two electrons. Feedback: Correct answers: 1. Catabolism 2. Matrix HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 46 MODULE 03 COMPANION GUIDE PHGY 170 3. Anabolism 4. ATP 5. Cristae 6. NAD+ SECTION 05: SUMMARY This content was retrieved from Section 05 Slide 11 of 11 of the online learning module. In this section, you learned about cellular metabolism. Cellular metabolism is the summation of all of the different reactions that take place in a cell, and can be catabolic or anabolic. ATP is the primary energy source for the cell. ATP is composed of an adenosine molecule, a ribose sugar, and three phosphates. The removal of the third phosphate releases energy, producing ADP and a free phosphate. Other high energy molecules include NADH and FADH2. Cellular metabolism takes place within the mitochondria, the power plants of the cell. In the next section, you will learn about the process of ATP production in the cell. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 47 MODULE 03 COMPANION GUIDE PHGY 170 SECTION 06: METABOLISM (A T P PRODUCTION) INTRODUCTION TO CELLULAR RESPIRATION ( ATP PRODUCTION) This content was retrieved from Section 06 Slide 2 of 29 of the online learning module. Cellular respiration is the term used to describe ATP production and comprises the catabolic reactions and processes that convert organic macromolecules into ATP. These numerous biochemical processes can be summarized as two components. Continue to learn what occurs in these processes. Removal of High-Energy Electrons High-energy electrons are stripped from these macromolecules and stored in high-energy electron carriers like NAD+ and FADH. Creation of a Proton Gradient High-energy electrons are combined with protons and molecular oxygen to create water. In these processes, energy is stored as a proton gradient* across the mitochondrial inner membrane and this gradient is then used to generate ATP. Definition*: Proton Gradient: A gradient that forms when there are different concentration of protons on one side of a cell membrane compared to the other (assuming that volume and pressure are constant). ENERGY STORAGE This content was retrieved from Section 06 Slide 3 of 29 of the online learning module. Many different organic compounds can be used to generate ATP. The primary sources are carbohydrates (simple and complex sugars), triglycerides (fats), and amino acids (proteins). Energy is stored in the body packaged in these biological molecules. Continue to learn about how energy is stored in each. Carbohydrates Carbohydrates are stored mainly as glycogen in muscles and the liver. Obviously, muscle glycogen is more readily available for actively working muscle use as liver glycogen needs to be broken down into glucose and secreted into the plasma. In times of glucose excess, glycogen stores are built up. Fats Fats are stored as triacylglycerols throughout the body. They must be broken down to release free fatty acids that need to be transported into the cells that need energy production. Protein HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 48 MODULE 03 COMPANION GUIDE PHGY 170 Proteins are stored mainly as skeletal muscle which is why there is muscle wasting if the body needs to use proteins as an energy source. This normally only happens in extended fasting. Note: In this section, you will learn about how ATP is produced from the simple sugar glucose. In Section 07, you will see how fats and proteins can also be used. STORING ATP This content was retrieved from Section 06 Slide 4 of 29 of the online learning module. Why isn’t energy just stored as ATP? It is much more efficient to store potential energy as carbohydrates, fats, and proteins than as A TP itself. If you think in terms of potential energy per gram, fat contains more energy than glycogen, and glycogen than ATP itself. Fat. Glycogen. ATP HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 49 MODULE 03 COMPANION GUIDE PHGY 170 Reference: Fat: Lents, N., Stark, L., & Denmark, B. (n.d.). Lipids: An introduction. Visionlearning. Retrieved March 2022, from: https://www.visionlearning.com/en/library/Biology/2/Lipids/207 Glycogen: Oiseth, S., Jones, L., & Maza, E. (2021, November 26). Glycogen Metabolism. Lecturio. Retrieved March 2022, from: https://www.lecturio.com/concepts/glycogen-metabolism/ ATP: By NEUROtiker - Own work, Public Domain. No reference required. Retrieved March 2022, from: https://commons.wikimedia.org/w/index.php?curid=2194476 SOURCES OF GLUCOSE FOR CELLULAR METABOLISM This content was retrieved from Section 06 Slide 5 of 29 of the online learning module. Carbohydrates are a major class of biological compounds. The most basic of these are what are commonly referred to as sugars. There are three types that vary by complexity. Continue to learn about the classes of carbohydrates and their significance. Monosaccharides, or “one sugar,” are most commonly consumed in the form of glucose, which is widely used as a sweetener. More complex are the disaccharides, which consist of two monosaccharides bonded by an α- or β-1,4- glycosidic linkage. An example of a disaccharide is lactose, found in milk, which consists of a molecule each of glucose and galactose. Even more complex are the polysaccharides, which are much longer chains of monosaccharides. Polysaccharides, such as glycogen, act as energy storage molecules and must be broken down before they can be used to produce cell energy. GETTING GLUCOSE INTO CELLS This content was retrieved from Section 06 Slide 6 of 29 of the online learning module. In order for ATP to be produced from glucose, it must first get into the cell, where ATP is produced. Cytoplasmic glucose is the primary substrate for the process of glycolysis that occurs in the cytoplasm. Glucose first enters the bloodstream from ingested foods, through de novo synthesis* in the body, or from the breakdown of glycogen stores. Once in the blood, glucose circulates and is available for cells to use. The most common way to get glucose into cells is by glucose transporters (GLUT) found in most mammalian cells. Definition*: De Novo Synthesis: The formation of complex molecules in the body from simpler molecules. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 50 MODULE 03 COMPANION GUIDE PHGY 170 THE 10 STEPS OF GLYCOLYSIS This content was retrieved from Section 06 Slide 7 of 29 of the online learning module. Glycolysis is a 10-step (or 10 reaction) process that breaks down glucose and transfers its energy into high-energy electron carriers and ATP. Why are there 10 steps? Catabolic reactions are exothermic, meaning that they give off heat. Glucose has a lot of energy stored within it and if all of that energy was released at the same time, it would likely kill the cell. The 10-step process allows the energy stored in glucose to be released a little at a time so that it can be efficiently transferred to other molecules with only a small amount lost as heat. The 10-step process also allows other monosaccharides such as fructose and galactose to enter glycolysis, as they can be converted into one of the intermediary products that are inserted into the process at a later stage. Other monosaccharides entering glycolysis, however, do not result in the same energy yield as glucose. GLYCOLYSIS IN THREE STAGES This content was retrieved from Section 06 Slide 8 of 29 of the online learning module. The 10 steps of glycolysis are commonly combined into three stages that help to summarize the overall process. Continue to learn about the three stages of glycolysis. STAGE 1 – Refer to page 51 STAGE 2 – Refer to pages 51-52 STAGE 3 – Refer to page 52 STAGE 1 OF GLUCOSE METABOLISM Sub-page of Glycolysis in Three Stages – STAGE 1 1/1 The first stage of glycolysis converts one glucose molecule into two glyceraldehyde 3-phosphate molecules (G3P) molecules using the first five reactions, the details of which you are not required to know. This first stage requires an investment of energy in the form of 2 ATP. Therefore, the net high-energy molecule count is a loss of 2 ATP. Use the counter to keep track of the net output of high-energy molecules. STAGE 2 OF GLUCOSE METABOLISM Sub-page of Glycolysis in Three Stages – STAGE 2 1/1 HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 51 MODULE 03 COMPANION GUIDE PHGY 170 Each G3P molecule enters the sixth and seventh reactions and is converted to a molecule called 3- phosphoglycerate. For each G3P, this stage produces 1 ATP and 1 NADH, a high-energy electron carrier, thus there is a total of 2 ATP and 2 NADH produced in these reactions. By the end of this stage of glycolysis, net ATP production is 0 and net NADH production is 2. Use the counter to keep track of the net output of high-energy molecules. STAGE 3 OF GLUCOSE METABOLISM Sub-page of Glycolysis in Three Stages – STAGE 3 1/1 The final stage of glycolysis starts with 3-phosphoglycerate and uses three reactions to convert it to pyruvate*. For each 3-phosphoglycerate, this stage produces 1 pyruvate and generates 1 ATP, thus there is a total of 2 pyruvate and 2 ATP produced in these reactions. By the end of this stage of glycolysis, one glucose molecule has been converted to 2 pyruvate and has produced 2 ATP and 2 NADH. Use the counter to keep track of the net output of high-energy molecules. Definition*: Pyruvate: The end product of glycolysis, and this can be further used in the Krebs cycle (in the presence of oxygen or anaerobically). SUMMARY OF GLYCOLYSIS This content was retrieved from Section 06 Slide 9 of 29 of the online learning module. The figure gives a summary of all 10 steps required to convert six-carbon glucose to two three-carbon pyruvate in the cytosol. This process can be summarized by the reaction: Glucose + 2 ADP + 2 NAD+ produces 2 pyruvate + 2 ATP + 2 NADH You should now be asking yourself what happens to these products. Is the final step of glucose metabolism to produce pyruvate? The answer is no; pyruvate has several fates, one of which is to produce even more energy. THE FATES OF PYRUVATE This content was retrieved from Section 06 Slide 10 of 29 of the online learning module. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 52 MODULE 03 COMPANION GUIDE PHGY 170 As you just learned, pyruvate is not the endpoint of glucose metabolism. All of the enzymatic reactions of glycolysis are reversible, meaning that if pyruvate or one of the intermediary products were to accumulate to a sufficient concentration, then it is possible that the forward conversion of glucose to pyruvate would stop and discontinue ATP production. Therefore, in order to prevent this, pyruvate must be further processed. How this occurs is dependent on whether or not molecular oxygen is present; anaerobic metabolism occurs without oxygen and aerobic occurs in the presence of oxygen. In the next slides, you will learn more about anaerobic metabolism and aerobic respiration. A pyruvate molecule. Reference: Wikimedia Commons. By Benjah-bmm27. Retrieved March 2022, from: https://en.wikipedia.org/wiki/File:Pyruvate_skeletal.svg ANAEROBIC METABOLISM This content was retrieved from Section 06 Slide 11 of 29 of the online learning module. Anaerobic metabolism occurs in the absence of oxygen. In this scenario, pyruvate undergoes fermentation so that the high-energy molecule NADH can be oxidized to NAD+. This allows NAD+ to be regenerated so glycolysis can continue to make ATP. Anaerobic metabolism produces one of two products. Continue to learn more about the products of anaerobic metabolism. HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 53 MODULE 03 COMPANION GUIDE PHGY 170 Anaerobic metabolism. Lactate In most animal cells and bacteria, pyruvate is reduced to lactate (lactic acid). Some bacteria use this pathway to ferment milk and make cheese. Ethanol HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 54 MODULE 03 COMPANION GUIDE PHGY 170 In plant cells and yeast, pyruvate is reduced to ethanol. In either case, the NADH produced during glycolysis is consumed, later resulting in a net yield of 2 ATP per glucose molecule. QUESTION: ANAEROBIC METABOLISM This content was retrieved from Section 06 Slide 12 of 29 of the online learning module. You have now learned about anaerobic metabolism. Answer the question using what you have learned and what you already know. Question 1 of 1: When do you think lactate is produced in humans? a) During rest b) During heavy exercise c) During eating and digestion d) During sudden changes in temperature Feedback: Correct Answer: B When you exercise, your body uses oxygen to break down glucose and produce energy. During heavy exercise, oxygen delivery to skeletal muscles is not sufficient, so anaerobic metabolic processes occur and lactate is produced. THE STAGES OF AEROBIC RESPIRATION This content was retrieved from Section 06 Slide 13 of 29 of the online learning module. In the presence of oxygen, far more ATP can be produced than by glycolysis alone. Aerobic respiration takes place in the mitochondria. On the next slides, you will learn about each of the five stages of aerobic respiration in more detail: 1. The conversion of pyruvate to acetyl-CoA 2. Krebs cycle 3. The electron transport chain 4. Chemiosmotic gradient 5. Formation of ATP by ATP synthase HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 55 MODULE 03 COMPANION GUIDE PHGY 170 Energy carriers and ATP produced through glucose metabolism. CONVERTING PYRUVATE TO ACETYL -COA This content was retrieved from Section 06 Slide 14 of 29 of the online learning module. At the end of glycolysis, pyruvate is in the cytosol of the cell and must be transported into the mitochondria, the site of ATP production. A carrier molecule on the inner mitochondrial membrane brings pyruvate into the matrix. In the matrix, pyruvate is decarboxylated* by the pyruvate dehydrogenase complex. During this process, many things happen. This complex takes the pyruvate, an NAD+, and a CoA molecule and converts them into acetyl-CoA, N ADH, and CO2. The acetyl-CoA molecule can then enter the Krebs Cycle. Recall that one glucose yields two pyruvate, so the net energy production of this stage is: 2 NADH. Metabolic pathway from glucose to acetyl-CoA. ATP NADH FADH2 2 4 0 HUMAN CELL PHYSIOLOGY | PHGY 170 MODULE 03 PAGE 56 MODULE 03 COMPANION GUIDE PHGY 170 Definition*: Decarboxylated: Having undergone decarboxylation, the removal of a carboxyl group (CO2). Reference: Plopper, G., & Ivankovic, D. B. (2020). Principles of Cell Biology (3rd ed.; pp. 471). Jones & Bartlett Learning, LLC. http://ebookcentral.proquest.com/lib/queen-ebooks/detail.action?docID=6002586 KREBS CYCLE This content was retrieved from Section 06 Slide 15 of 29 of the online learning module. The Krebs cycle, also called the tricarboxylic acid (TCA) cycle or the citric acid cycle, is a complex series of chemical reactions. The function of these reactions is to complete the oxidation of carbohydrates, proteins, and fats to produce the substrates for cellular energy production. For the purpose of this course, it is not necessary to memorize each and every step of the cycle but rather to focus on the key concepts here. Continue for an overview of the Krebs cycle. Acetyl-CoA Acetyl-CoA enters the Krebs cycle by combining with oxaloacetate to form citrate, a six-carbon molecule. Recall that glycolysis began with glucose, a six-carbon molecule, so you should already be thinking that a lot of energy is now stored in citrate, you just need to get it out. At this stage, CoA is released and can be recycled to produce more acetyl-CoA. Citrate Citrate (six-carbons) is broken down by several chemical reactions to remove two of the carbons and create succinate. This removal of carbons transfers energy to two NAD+ to form two NADH and releases the carbons in the form of two CO2, and one guanosine triphosphate (GTP; a nucleoside triphosphate like ATP) is also produced. Succinate To complete the cycle, succinate is converted back to oxaloacetate by multiple processes. These proc

PHGY 170 Module 03: The Plasma Membrane and Mitochondria PDF

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