Cell Science - MPharm Programme PDF

MPharm Programme Cell Science ‐ Introduction to Cellular Structure 1 & 2 Dr Praveen Bhugra PHA115 Slide 1 of 69 PHA115 Cellular Structure 1 & 2  Learning Objectives...

MPharm Programme Cell Science ‐ Introduction to Cellular Structure 1 & 2 Dr Praveen Bhugra PHA115 Slide 1 of 69 PHA115 Cellular Structure 1 & 2  Learning Objectives By the end of this lecture you should be able to understand and be able to explain in detail following Cell Theory Stem cells theory Difference between Prokaryotic and Eukaryotic cells Differentiation between plant cell, animal cell and bacteria Structure and function of three main parts of cell (Plasma Membrane; Cytoplasm [cytosol and cell organelles] and Nucleus) Slide 2 of 69 PHA115 Cellular Structure 1 & 2  Cells Theory The basic concept of the cell theory can be summarized as follows; Cells are building blocks of all plants and animal All cells come from the division of preexisting cells Cells are the smallest units that perform all vital physiological functions Each cell maintains homeostasis at the cellular level Slide 3 of 69 PHA115 Cellular Structure 1 & 2  Cells in the human body All the parts of your body are made up of cells There are an estimated 3.72x1013 cells in the body (Bianconi et al., (2013) Ann Human Biol. 40, 463‐71) There is no such thing as a typical cell The body has many different kinds of cells Though they might look different under a microscope, most cells have chemical and structural features in common In humans, there are about 200 different types of cells, and within these cells there are about 20 different types of structures or organelles Slide 4 of 69 PHA115 Cellular Structure 1 & 2  Diversity of Human Cells Adult humans consist of more than 200 kinds of cells. They are nerve cells (neurons), muscle cells (myocytes), skin (epithelial) cells, blood cells (erythrocytes, monocytes, lymphocytes, etc.), bone cells (osteocytes), and cartilage cells (chondrocytes). Cells essential for embryonic development but not incorporated into the body of the embryo, include the extra-embryonic tissues, placenta, and umbilical cord. All of these cells are generated from a single, totipotent cell, the zygote, or fertilized egg Slide 5 of 69 PHA115 Cellular Structure 1 & 2  Diversity of Human Cells Erythrocytes Fibroblasts Epithelial cells (a) Cells that connect body parts, Nerve cell form linings, or transport gases Skeletal Smooth (e) Cell that gathers information Muscle muscle cells and control body functions cell (b) Cells that move organs and Sperm body parts Macrophage (f) Cell of reproduction Fat cell (c) Cell that stores(d) Cell that nutrients fights disease Slide 6 of 69 PHA115 Cellular Structure 1 & 2  Diversity of Human Cells Slide 7 of 69 PHA115 Cellular Structure 1 & 2  Stem cells Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells In mammals, there are two broad types of stem cells: – embryonic stem cells isolated from the inner cell mass of blastocysts – adult stem cells, which are found in various tissues In adults, stem cells and progenitor cells act as a repair system for the body In a developing embryo, stem cells can differentiate # into all the specialized cells—ectoderm, endoderm and mesoderm (germ layers ‐ which give rise to ALL the bodies tissues and organs) Slide 8 of 69 PHA115 Cellular Structure 1 & 2  Stem cells (Growth and development of the embryo) Slide 9 of 69 PHA115 Cellular Structure 1 & 2  Stem cells Slide 10 of 69 PHA115 Cellular Structure 1 & 2  Stem cells potency Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell Totipotent (or omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable organism. These cells are produced from the fusion of an egg and sperm cell. Pluripotent stem cells are the descendants of totipotent cells and can differentiate into nearly all cells, i.e. cells derived from any of the three germ layers Multipotent stem cells can differentiate into a number of cell types, but only those of a closely related family of cells * Oligopotent stem cells can differentiate into only a few cell types, such as lymphoid or myeloid stem cells Unipotent cells can produce only one cell type, their own, but have the property of self‐renewal, which distinguishes them from non‐stem cells Slide 11 of 69 PHA115 Cellular Structure 1 & 2  Stem cells potency Slide 12 of 69 PHA115 Cellular Structure 1 & 2  Stem cell division and differentiation A: stem cell * B: progenitor cell C: differentiated cell 1. symmetric stem cell division 2. asymmetric stem cell division 3. progenitor division 4. terminal differentiation Slide 13 of 69 PHA115 Cellular Structure 1 & 2  Stem cell division and differentiation Slide 14 of 69 PHA115 Cellular Structure 1 & 2  Potential uses of stem cells Slide 15 of 69 PHA115 Cellular Structure 1 & 2  Stem cells potency & source developmental Kidney has a RBC ensor > less RBC ↳ less 120 days oxygen older life span - oxygen - capacity promotes Blood circulation Erythropod a RBC = hormone Slide 16 of 69 PHA115 Cellular Structure 1 & 2  Hierarchy of haemopoietin differentiation B Cells T Cells NK Cells Plasmacytoid Dendritic Cell Monocytoid Dendritic Cell Monocyte Granulocyte Basophil Mast Cell Eosinophil RBCs Platelets Slide 17 of 69 PHA115 Cellular Structure 1 & 2  Characteristics of all cell types A surrounding membrane Protoplasm – cell contents in thick fluid Organelles – structures for cell function Control center with DNA On this basis we have: – Prokaryotic – Eukaryotic Slide 18 of 69 PHA115 Cellular Structure 1 & 2  Characteristics of all cell types Slide 19 of 69 PHA115 Cellular Structure 1 & 2  Prokaryotic Cells Cells that lack a nucleus or membrane-bound organelles Simplest type of cell Single, circular chromosome Nucleoid region (center) contains the DNA Surrounded by cell membrane & cell wall (peptidoglycan) Contain ribosomes (no membrane) in their cytoplasm to make proteins One-celled organisms, Bacteria Slide 20 of 69 PHA115 Cellular Structure 1 & 2  Prokaryotic Cells Cell walls -protect the cell and enzyme maintain cell shape =NAG · alanin NAM NAG NAM 1/ P lasmid : 25XDNA2t Bacterial cell walls InPenguine e Plasmic st gene S Fplasmid /antibiotics 1 - may be composed of ↳H - B-lactam kill peptidoglycan => [Renicillina P. C -may be Gram positive or Gram negative Archaean cell walls lack peptidoglycan. Flagella - present in some prokaryotic cells -used for locomotion and -rotary motion propels the cell Slide 21 of 69 PHA115 Cellular Structure 1 & 2  Prokaryotic Cells (Bacteria) Bacteria may be classified according to their response to Gram’s Stain Gram +ve Gram–ve Gram‐positive bacteria have a thick mesh‐like cell wall m + ElIOECE made of peptidoglycan (50‐90% of cell wall), which stain purple Gram‐negative bacteria have a thinner layer (10% of cellq(((LPS) mu + wall), which stain pink page) (next Slide 22 of 69 PHA115 Cellular Structure 1 & 2  Prokaryotic Cells (Bacteria) * Gram staining : PG Ht) : > - purple > purple purple [ - > - Crystal ethano THE : NI2tY H : - > purple > - white- > pink Gram positive S. aureus Gram negative E. coli Slide 23 of 69 PHA115 Cellular Structure 1 & 2  Prokaryotic Cells (Bacteria) Slide 24 of 69 PHA115 Cellular Structure 1 & 2  Prokaryotic Cells (Bacteria) microbiolog a Comparative Characteristics of Gram Positive and Gram Negative Bacteria Slide 25 of 69 PHA115 Cellular Structure 1 & 2  Eukaryotic Cells Possess a membrane-bound nucleus More complex than prokaryotic cells Compartmentalize many cellular functions within organelles and the endomembrane system Possess a cytoskeleton for support and to maintain cellular structure Include fungi, protozoa, plant, and animal cells Protozoan Slide 26 of 69 PHA115 Cellular Structure 1 & 2  Eukaryotic Cells u v V Slide 27 of 69 PHA115 Cellular Structure 1 & 2  Plant Cell Slide 28 of 69 PHA115 Cellular Structure 1 & 2  Animal Cell Slide 29 of 69 PHA115 Cellular Structure 1 & 2  * Cell Structure The three main parts of a cell 1. Plasma membrane 2. Cytoplasm: cytosol + organelles 3. Nucleus Cytoplasm Cytosol Slide 30 of 69 PHA115 Cellular Structure 1 & 2  Generalized View of Cell Structure Slide 31 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane Membranes form a major structural element in cells.  Phospholipid bilayer  Cholesterol  Proteins (integral and peripheral)  Attached carbohydrates (glycolipids and glycoproteins) Slide 32 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane Functions of membranes include:  Barrier between inside and outside of cell  Controls entry of materials: transport  Receives chemical and mechanical signals  Transmits signals between intra- and extra- cellular spaces Slide 33 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane (Phospholipids) Phospholipids are amphipathic. Organized into a bilayer with the nonpolar fatty acid chains in the middle. The polar regions of the phospholipids are oriented toward the surfaces of the membrane as a result of their attraction to the polar water molecules in the extracellular fluid and cytosol. Slide 34 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane (Phospholipids)  Fatty acid tails – hydrophobic  Phosphate group head – hydrophilic Slide 35 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane (Cholesterol) The plasma membrane also contains cholesterol, whereas intracellular membranes contain very little cholesterol. Cholesterol associates with certain classes of plasma membrane phospholipids and proteins, forming organized clusters that work together to pinch off portions of the plasma membrane to form vesicles that deliver their contents to various intracellular organelles. Slide 36 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane (Cholesterol) Cholesterol molecules are weakly amphipathic (paar polar The tiny —OH group is the only polar region of cholesterol, and it forms hydrogen bonds with the polar heads of phospholipids and glycolipids. The stiff steroid rings and hydrocarbon tail of cholesterol are nonpolar; they fit among the fatty acid tails of the phospholipids and glycolipids. Slide 37 of 69 PHA115 Cellular Structure 1 & 2  * Plasma Membrane (Cholesterol) Cholesterol has temperature dependent effects on membrane fluidity Warm temperatures – restrains phospholipid movement Cold temperatures – maintains fluidity by preventing tight packing Slide 38 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane (Glycolipids) The carbohydrate groups of glycolipids form a polar "head"; their fatty acid "tails" are nonpolar. Glycolipids appear only in the membrane layer that faces the extracellular fluid, which is one reason the two sides of the bilayer are asymmetric, or different. Slide 39 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane (Protein) There are two classes of membrane proteins: integral and peripheral. Integral membrane proteins Closely associated with the membrane lipids, cannot be extracted from the membrane without disrupting the lipid bilayer, and are amphipathic. Most integral proteins span the entire membrane and are referred to as transmembrane proteins. Most of these transmembrane proteins cross the lipid bilayer several times. Some transmembrane proteins form channels through which ions or water can cross the membrane, whereas others are associated with the transmission of chemical signals across the membrane or the anchoring of extracellular and intracellular protein filaments to the plasma membrane. Slide 40 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane (Protein) Peripheral membrane proteins Are not amphipathic and do not associate with the nonpolar regions of the lipids in the interior of the membrane. Located at the membrane surface where they are bound to the polar regions of the integral membrane proteins. Slide 41 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane (Protein) Many membrane proteins are glycoproteins, proteins with carbohydrate groups attached to the ends that protrude into the extracellular fluid. The carbohydrate portions of glycolipids and glycoproteins form an extensive sugary coat called the glycocalyx. Glycocalx acts like a molecular "signature" that enables cells to recognize one another Slide 42 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane (Protein) ↓ * ↓ - - m ↓ E mechanism ↓ moveclsas response Slide 43 of 69 PHA115 Cellular Structure 1 & 2  Plasma Membrane (Junctions) Many cells are physically joined by types of junctions: desmosomes, tight junctions, and gap junctions. Integrins are transmembrane proteins in the plasma membrane which bind to specific proteins in the extracellular matrix and link them to membrane proteins on adjacent cells. Slide 44 of 69 PHA115 Cellular Structure 1 & 2  Desmosomes Characterized by accumulations of protein known as dense plaques along the cytoplasmic surface of the plasma membrane. These proteins serve as anchoring points for cadherins. Cadherins are proteins that extend Tibre-like structure from the cell into the extracellular space, where they link up and bind with cadherins from an adjacent cell. Desmosomes hold adjacent cells firmly y together in areas that are subject to gaps considerable stretching, such as the skin. Slide 45 of 69 PHA115 Cellular Structure 1 & 2  Tight junctions Form when the extracellular surfaces of two adjacent plasma membranes join together so that no extracellular space remains between them. Unlike the desmosome, which is limited to a disk-shaped area of the membrane, the tight junction occurs in a band around Togaps the entire circumference of the cell. Slide 46 of 69 PHA115 Cellular Structure 1 & 2  Gap junctions Consist of protein channels linking the cytosols of adjacent cells. Connexins from the two membranes join, forming small, protein-lined channels linking the two cells. Diameter of about 1.5 nm limits what can pass between the cytosols of the connected cells to small molecules and ions, such as Na+ and K+, and excludes the exchange of large proteins. Satan's Example: Muscle cells of the heart cells Slide 47 of 69 PHA115 Cellular Structure 1 & 2  Functions of Cell Membranes 1. Regulate the passage of substances into and out of cells and between organelles and cystosol 2. Detect chemical messengers arriving at the cell surface 3. Link adjacent cells together by membrane junctions 4. Anchor cells to the extracellular matrix Slide 48 of 69 PHA115 Cellular Structure 1 & 2  Cytoplasm Slide 49 of 69 PHA115 Cellular Structure 1 & 2  Cytoplasm (Cytosol) Lorganelle + cytosol * Fluid portion of cytoplasm that surrounds organelles. Constitutes about 55% of total cell volume. Cytosol is 75-90% water plus various dissolved and suspended components (such as ions, glucose amino 9) acids, fatty acids, proteins, lipids, ATP, and waste products. Also present in some cells are various organic molecules that aggregate into masses for storage; which may appear and disappear at different times in the life of a cell. Cytosol site of many chemical reactions required for a cell's existence. Slide 50 of 69 PHA115 Cellular Structure 1 & 2  Cytoplasm (Cell Organelles) Cytoskeleton Flagella, cilia & centrioles Endoplasmic reticulum Golgi apparatus Mitochondrion Nucleus, nucleolus, nuclear envelope Vesicles, e.g. lysosome Slide 51 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Cytoskeleton) Maintains shape of cell Positions organelles Changes cell shape Includes: microfilaments, intermediate bigger diametre V filaments, microtubules Slide 52 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Cytoskeleton) Microfilaments (also called Actin filaments) and Microtubules can be assembled and disassembled rapidly, allowing a cell to alter these components of its cytoskeletal framework according to changing requirements. Intermediate filaments, once assembled, are less readily disassembled. = Actin filaments Slide 53 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Centrosome) Structure: – Two centrioles arranged perpendicular to each other Composed of microtubules: 9 clusters of 3 (triplets) – Pericentriolar material Composed of tubulin that grows the mitotic spindle Function: moves chromosomes to ends of cell during cell division Slide 54 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Cilia and Flagella) Specialized for Doublet motion microtubules Cilium or Flagellum: single tail flagellum Central like structure on pair of sperm microtubules Plasma – Propels sperm membrane forward in reproductive tract Basal body Cilia: in groups – Found in respiratory system: move mucus Slide 55 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles Ribosomes Made within the nucleus (in nucleolus) Sites of protein synthesis (on E.R. or freely within cytoplasm) Consist of ribosomal RNA (rRNA) + proteins Contain large and small subunits Can be attached to endoplasmic reticulum or free in cytosol Slide 56 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Endoplasmic Reticulum (E.R.)) Structure: network of folded membranes Functions: synthesis, intracellular transport Types of E.R. – Rough E.R.: studded with ribosomes (sites of protein synthesis) too much glucose in bloodstream – Smooth E.R. lacks ribosomes. viscosity ↓ t Functions: ↓ slower movements Y – lipid synthesis many cause problems (ex. Cardiac * – release of glucose in liver cells into bloodstream – drug detoxification (especially in liver cells) – storage and release of Ca2+ in muscle cells (where smooth E.R. is known as sarcoplasmic reticulum or SR) Slide 57 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Endoplasmic Reticulum (E.R.)) Slide 58 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Golgi Complex) Structure: – Flattened membranes (cisterns) with bulging edges (like stacks of pita bread) Functions: – Modify proteins  glycoproteins and lipoproteins that: Become parts of plasma membranes Are stored in lysosomes, or Are exported by exocytosis Slide 59 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Lysosomes) Structure: – Spherical or oval surrounded by single membrane – Typical cell may contain several hundred lysosomes Functions: Contain variety of digestive enzymes Help in final processes of digestion within cells Carry out autophagy (destruction of worn out parts of cell) and death of old cells (autolysis) Tay-Sachs: hereditary disorder; one missing lysosomal enzyme leads to nerve destruction Slide 60 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Peroxisomes) Structure : – are moderately dense oval bodies enclosed by a single membrane. Function: – consume molecular oxygen and it undergoes reactions that remove hydrogen from organic molecules including lipids, alcohol, and potentially toxic ingested substances. Detoxify; abundant in liver Slide 61 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Proteasomes) Structure : – Tiny barrel shaped structure that contain proteases (proteolytic enzyme). Function: – Digest unneeded or faulty proteins ~ ↓ – Faulty proteins accumulate in brain cells in persons with Parkinson or Alzheimer disease. Slide 62 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Mitochondria) Structure: – Sausage-shaped with many folded membranes (cristae) nu and liquid matrix - containing enzymes – Have some DNA, ribosomes (can make proteins) Slide 63 of 69 PHA115 Cellular Structure 1 & 2  Cell Organelles (Mitochondria) Function: – Major site of ATP production , O2 utilization and CO2 formation – Contains enzyme active in Kreb’s cycle and oxidative phosphorylation Abundant in muscle, liver, and kidney cells – These cells require much ATP Slide 64 of 69 PHA115 Cellular Structure 1 & 2  Nucleus Round or oval structure surrounded by nuclear envelope with nuclear pores Contains nucleolus: makes ribosomes that pass into cytoplasm through nuclear pores Within the nucleus, DNA, in association with proteins, forms a fine network of threads known as chromatin Slide 65 of 69 PHA115 Cellular Structure 1 & 2  Nucleus Most prominent structure in the nucleus is the nucleolus. – Densely staining filamentous region without a membrane. – Associated with specific regions of DNA that contain the genes for forming the particular type of RNA found in cytoplasmic organelles called ribosomes. – Store genetic material (DNA) in genes arranged in 46 chromosomes (the human genome containing 30,000 genes!) – DNA contains information for directing protein synthesis: In the cell In new cells (formed by cell reproduction) Slide 66 of 69 PHA115 Cellular Structure 1 & 2  Comparison of Bacterial, Animal and Plant cells MCQ Slide 67 of 69 PHA115 Cellular Structure 1 & 2  Cells Parts and Their Functions Slide 68 of 69 PHA115 Cellular Structure 1 & 2  Further Reading Refer to the Following Textbooks Ross and Wilson Anatomy and Physiology in Health and illness 13th Edition Gerard J. Tortora and Byran H. Derrickson Principles of Anatomy and Physiology 13th Edition Frederic H. Martini Fundamentals of Anatomy & Physiology 7th Edition Elaine N. Marieb and Katja Hoehn Human Anatomy & Physiology 8th Edition VanPutte, Regan and Russo Seeley’s Anatomy and Physiology 12th Edition Slide 69 of 69 PHA115 Cellular Structure 1 & 2  MPharm Programme Cell Science - Cellular Process 1 & 2 Dr Praveen Bhugra PHA115 Slide 1 of 43 PHA115 Cellular Process  Learning Objectives From this lecture you should be able to: – Understand and explain in detail the different transport processes into and out of cells (Passive Process; Active Process; Transport in Vesicles) – Understand and explain how substances are transported across membranes – Understand, explain and give examples of the different transport processes and how they apply to the functioning of cells and the body including nervous system and neurotransmission Slide 2 of 43 PHA115 Cellular Process  Terminology: Body Fluid Pools Intracellular (ICF) cytosol – Within cells: 2/3 of total ~ Extracellular (ECF): – Between cells = Interstitial – In blood vessels = Plasma~ RBC WBC. – In lymphatic vessels = Lymphatic fluid ( Lymph) – Within the brain and spinal cord - cerebrospinal fluid Slide 3 of 43 PHA115 Cellular Process  Terminology: Solutions Solvent: the liquid doing the dissolving – Usually water Solute: the dissolved material (particles or gas) Concentration – Amount of solute in a given amount of solvent Concentration gradient * – Difference in concentration between 2 areas of - solution a I inside outside posmerone Slide 4 of 43 PHA115 Cellular Process  Molecule movement across membranes (Gradients Across the Plasma Membrane ) Selective permeability : allows a living cell to maintain different concentrations of certain substances on either side of the plasma membrane. Concentration gradient :difference in the concentration of a chemical from one place to another (from the inside to the outside of the plasma membrane). Difference in electrical charges between two regions constitutes an electrical gradient. out sodium much + ↑ Or) Too in potassiumon 201 Slide 5 of 43 PHA115 Cellular Process - weath  Molecule movement across membranes (Gradients Across the Plasma Membrane) Electrical gradient occurs across the plasma membrane, this charge difference is termed the membrane potential. The concentration gradient and electrical gradient are important because they help move substances across the plasma membrane. The combined influence of the concentration gradient and the electrical gradient on movement of a particular ion is referred to as its electrochemical gradient. Slide 6 of 43 PHA115 Cellular Process  Molecule movement across membranes Passive Transport ( Passive Processes) - no E required Active Transport (Active Processes) - E required Endocytosis – Phagocytosis – Fluid endocytosis (pinocytosis) – Receptor – mediated endocytosis Exocytosis V insulin ↓ stimulates - neurotransmitter thyrocin ↓ glucose Jname ? transportraise E glucose in goes Slide 7 of 43 PHA115 Cellular Process  Types of Passive Transport Simple diffusion Facilitated diffusion Osmosis Slide 8 of 43 PHA115 Cellular Process  The Principle of Diffusion Diffusion is a passive process in the random mixing of particles in a solution occurs because of the particles' kinetic energy. Both the solutes, the dissolved substances, and the solvent, the liquid that does the dissolving, undergoing diffusion. Slide 9 of 43 PHA115 Cellular Process  Factors Influencing Diffusion L facilitators Steepness of the concentration gradient: Difference in concentration between the two sides of the membrane, the higher the rate of diffusion Temperature : Higher temperature, the faster the rate of diffusion Mass of the diffusing substance: Larger the mass of the diffusing particle, the slower its diffusion rate Surface area: Larger the membrane surface area available for diffusion, the faster the diffusion rate Diffusion distance: Greater the distance over which diffusion must occur, the longer it takes Slide 10 of 43 PHA115 Cellular Process  Simple Diffusion No energy required Move due to gradient – differences in concentration, pressure, charge Move to equalize gradient – High moves > - ? toward low - Depends on Lipid solubility Slide 11 of 43 PHA115 Cellular Process  Simple Diffusion Slide 12 of 43 PHA115 Cellular Process  Facilitated Diffusion Solutes too polar or highly charged to move through the lipid bilayer by simple diffusion; cross the plasma membrane by a passive process called facilitated diffusion. Requires a carrier in membrane but not ATP Solute goes down concentration gradient Facilitated Diffusion through – Ion Channels – Protein transporters (also called carriers) Slide 13 of 43 PHA115 Cellular Process  Facilitated Diffusion (Ion Channel) Ion channels, integral transmembrane proteins that allow passage of small, inorganic ions that are too hydrophilic to penetrate the nonpolar interior of the lipid bilayer. Ions such as Na+, K+, Cl–, and Ca++ all use specific protein channels to diffuse into and out of cells Channel is gated when part of the channel protein acts as a "plug" or "gate," changing shape in one way to open the pore and in another way to close it Types of Gated channels : semipermeable membrane – Ligand gated ↳ smal/soluble enough molecules – Voltage gated ex) oxygen – Mechanically gated Slide 14 of 43 PHA115 Cellular Process  Facilitated Diffusion (Ion Channel) Channel-mediated facilitated diffusion of potassium ions (K+) through a gated K+ channel. Slide 15 of 43 PHA115 Cellular Process  Facilitated Diffusion (Carriers ) A carrier (also called a transporter) is used to move a solute down its concentration gradient across the plasma membrane Solute binds more often to the carrier on the side of the membrane with a higher concentration of solute Carriers are occupied, the transport maximum is reached, the process of carrier-mediated facilitated diffusion exhibits saturation Substances that move across the plasma membrane by carrier mediated facilitated diffusion include glucose, fructose, galactose and some vitamins Slide 16 of 43 PHA115 Cellular Process  Facilitated Diffusion (Carriers ) Glucose enters many body cells by diffusion as follows : 1. Binds to specific carrier protein - Glucose transporter on the outside of the cell surface 2. Transporter undergoes a change in shape , glucose passes the membrane 3. Transporter releases glucose on the other side of the membrane Slide 17 of 43 PHA115 Cellular Process  Osmosis Special form of diffusion Diffusion of water through a semi-permeable membrane · osmotic pressure pulls water from diluted Permeable to solvent ~ => concentrated osmosis proceeds solution until uilibrium is reached Impermeable to solute some conc. different vol. = isotonic) During osmosis, water molecules pass through a plasma membrane in two ways: 1. By moving through the lipid bilayer via simple diffusion, as previously described 2. By moving through aquaporins , integral membrane proteins that function as water channels. Slide 18 of 43 PHA115 Cellular Process  Osmosis Slide 19 of 43 PHA115 Cellular Process  Osmolarity The total solute concentration of a solution is known as its osmolarity. One osmol is equal to 1 mol of solute particles. So a 1 M solution of glucose has a concentration of 1 Osm (1 osmol per liter), whereas a 1 M solution of sodium chloride contains 2 osmol of solute per liter of solution. A liter of solution containing 1 mol of glucose and 1 mol of sodium chloride has an osmolarity of 3 Osm. Although osmolarity refers to the concentration of solute particles, it also determines the water concentration in the solution because the higher the osmolarity, the lower the water concentration. Slide 20 of 43 PHA115 Cellular Process  Tonicity The ability of a solution to change the shape or tone of cells by altering their internal water volume is called tonicity. L normal u * apply in a clinkal situation Figure: The effect of solutions of varying tonicities on living red blood cells Slide 21 of 43 PHA115 Cellular Process  Active Transport Uses energy to move molecules against the concentration H+ L gradient. These transporters are often called “pumps”. These pumps can also be saturated and use two types of energy sources: (1) The direct use of ATP in primary active transport un (2) The use of an electrochemical gradient across a membrane to drive the process in secondary active transport Slide 22 of 43 PHA115 Cellular Process  Primary Active Transport The Na+/K+-ATPase primary active transporter is found in every cell and helps establish and maintain the membrane potential of the cell. In addition to the Na+/K+-ATPase transporter, the major primary active-transport proteins found in most cells are: (1) Ca2+- ATPase ( (2) H+- ATPase (3) H+/K+ -ATPase Slide 23 of 43 PHA115 Cellular Process  Primary Active Transport 1. Cytoplasmic Na+ binds to 2.Binding of Na+ promotes 3.Phosphorylation causes pump protein. phosphorylation of the the protein to change protein by ATP. shape, expelling Na+ to the outside 6.K+ is released from the 5.K+ binding triggers pump protein and Na+ sites release of the phosphate. Pump protein returns to 4.Extracellular K+ binds to are ready to bind Na+ again. its original conformation. pump protein. The cycle repeats. Slide 24 of 43 PHA115 Cellular Process  Secondary Active Transport Secondary active transport is distinguished from primary active transport by its use of an electrochemical gradient across a plasma membrane as its energy source. Transporters that mediate secondary active transport have two binding sites, one for an ion (e.g., Na+)and another for the cotransported molecule (e.g., Glucose). Co-transporters (symporters) move molecules in the same direction. Counter-transporters (antiporters) move molecules in opposite directions Slide 25 of 43 PHA115 Cellular Process Slide 26 of 43 PHA115 Cellular Process  Vesicular Transport Endocytosis involves the movement of macromolecules into the cell by the pinching of the plasma membrane into membrane bound vesicles Exocytosis involve the movement of macromolecules out of the cell by the fusion of membrane bound vesicles to the plasma membrane Slide 27 of 43 PHA115 Cellular Process  Vesicular Transport - Endocytosis Packaging of extracellular materials in vesicles at the cell surface Involves relatively large volumes of extracellular material Requires energy in the form of ATP. Three major types 1.Receptor-mediated endocytosis 2.Pinocytosis 3.Phagocytosis Slide 28 of 43 MPharm PHA115 Cellular Process  Receptor Mediated Endocytosis A highly selective process A vesicle forms after a receptor protein in the plasma membrane recognizes and binds to a particular particle in the extracellular fluid. Examples: cells take up cholesterol-containing low-density lipoproteins (LDLs), transferrin (an iron-transporting protein in the blood), some vitamins, antibodies, and certain hormones Involves formation of vesicles at surface of membrane Clathrin-coated vesicle in cytoplasm Slide 29 of 43 MPharm PHA115 Cellular Process  Receptor mediated endocytosis exam 5 options 1 ~ ↑ options * MCQ ; remember the process 1. Binding 2. Vesicle formation 3. Un-coating 4. Fusion with endosome 5. Recycling of receptors to plasma membrane 6. Degradation in lysosomes Slide 30 of 43 MPharm PHA115 Cellular Process  Pinocytosis Plasma membrane forms an invagination, sinks inward, pinches off and forms a vesicle Materials dissolve in water to be brought into cell Called “cell drinking” The most common form of endocytosis in most cells, especially absorptive cells in the intestines and kidneys Most proteins and other large molecules are taken up this way Slide 31 of 43 MPharm PHA115 Cellular Process  Phagocytosis Used to engulf large, solid particles such as food, bacteria, etc. into vesicles Cell eating A few body cells, termed phagocytes, are able to carry out phagocytosis Vital defence mechanism that helps protect the body from disease. Slide 32 of 43 MPharm PHA115 Cellular Process  Exocytosis Movement of molecules out of the cell via vesicles. Exocytosis performs several functions for cells: 1. Provides a way to replace portions of the plasma membrane that endocytosis has removed 2. Adds new membrane components to the membrane 3. Provides a route by which membrane- impermeable molecules (such as protein hormones) the cell synthesizes can be secreted into the extracellular fluid Slide 33 of 43 MPharm PHA115 Cellular Process  Exocytosis (Process) & * +- SNARE SNARE [v-SNARE 1. The membrane-bound vesicle 2. There, proteins at the vesicle surface (v-SNAREs) migrates to the plasma membrane bind with t-SNAREs (plasma membrane proteins). release synaptic Junction , etc. 4. Vesicle contents are released to 3. The vesicle and plasma membrane the cell exterior fuse and a pore opens up. Slide 34 of 43 MPharm PHA115 Cellular Process  Exocytosis Exocytic vesicle immediately after fusion with plasma membrane. Slide 35 of 43 MPharm PHA115 Cellular Process  Exocytosis Cytoplasmic vesicle merges with the plasma membrane and releases its contents - exo (out) Requires energy (ATP) and Ca2+ ions U to make Example: things move – Golgi body vesicles merge with the plasma membrane and release their contents – Nerve cells release neurotransmitters e.g. acetylcholine (ACh), noradrenaline (NA) etc. are stored in vesicles – Hormones are released e.g. insulin from storage vesicles in β-cells of pancreas Slide 36 of 43 MPharm PHA115 Cellular Process  Exocytosis and Nervous System Function A nerve cell communicates to another cell by releasing chemicals via exocytosis at the synaptic ~ ex1 acetylcholine terminal > signalling - Slide 37 of 43 MPharm PHA115 Cellular Process  Exocytosis and Nervous System Function signals Slide 38 of 43 MPharm PHA115 Cellular Process  Exocytosis in Presynaptic Neuron STEPS un I interiora ↓ starts Bott moving to plasma membrane synaptic cleft Slide 39 of 43 MPharm PHA115 Cellular Process  Process of neurotransmission u Slide 40 of 43 MPharm PHA115 Cellular Process  Transcytosis Used to successively to move a substance into, across, and out of a cell. Active process Vesicles undergo endocytosis on one side of a cell, move across the cell, and then undergo exocytosis on the opposite side. Occurs most often across the endothelial cells that line blood vessels and when a woman is pregnant, some of her antibodies cross the placenta into the foetal circulation via transcytosis vesicle merges with the plasma membrane and releases its contents Slide 41 of 43 MPharm PHA115 Cellular Process  # Summary of Transport Processes 1kot oflet ! im. (passive) 21 3) + transcytosis Slide 42 of 43 MPharm PHA115 Cellular Process  Further Reading Refer to the Following Textbooks Ross and Wilson Anatomy and Physiology in Health and illness 13th Edition Gerard J. Tortora and Byran H. Derrickson Principles of Anatomy and Physiology 13th Edition Frederic H. Martini Fundamentals of Anatomy & Physiology 7th Edition Lauralee Sherwood Human Physiology from cells to systems 7th Edition Walter F. Boron and Emile L. Boulpaep Medical Physiology 3th Edition Slide 43 of 43 PHA115 Cellular Process