Biology of the Cell PDF

Chapter 4 Biology of the Cell Basic, living, structural & functional unit – Organismal activity – Compartment s – Regulation inflow & outflow of materials – Controlled by genes Cytology Cell physiology 1  G...

Chapter 4 Biology of the Cell Basic, living, structural & functional unit – Organismal activity – Compartment s – Regulation inflow & outflow of materials – Controlled by genes Cytology Cell physiology 1  Generalized Cell Structures Plasma mb = cell mb – Boundary – Controls traffic – Determines solubility & fxn Nucleus Cytoplasm – Cytosol – Organelles 2  Plasma Membrane Fluid mosaic Glycolipids model Glycoproteins – Phospholipid bilayer – Amphipathic 3  Peripheral Membrane Proteins vs. Integral Membrane Proteins – Transmembrane Proteins 4  Functions of Membrane Proteins Mb proteins vary in different cells Different proteins help to determine many of the fxns of the plasma mb Functions: – Transport Proteins – 1) Channels/pores – 2) Carrier/pump (transporter) – 3) Receptors – 4) Enzymes – Linkers – 5) Anchoring Sites – 6) Cell-adhesion proteins – 7) Cell-identity markers 5  Membrane Fluidity Mb are fluid – Sensitive to temperature – Self-sealing if punctured Freely moveable – Need to stay in one half of lipid bilayer – Cholesterol reduces 6  Selectively Permeable Mb Impermeable to: – Macromolecul es – Tiny charged molecules Permeable to: – Small, uncharged molecules 7 Gradients Across the Plasma Mb Concentration gradient – Ions have electrochemical gradients Substances move w/ concentration gradient 8  Transportation Across Cell Membrane Passive transport Moves DOWN concentration gradient – Simple diffusion – Osmosis (water) – Facilitated diffusion – Through channel – Through carrier Active transport Require ATP – Primary – Secondary – Vesicular transport 9 Overview of Membrane Transport 10  Principles of Diffusion Random mixing of particles results from KE Rate of diffusion varies – Concentration – Temperature – Surface area – Size of molecule – Diffusion distance Dynamic equilibrium 11 Osmosi s Diffusion of H2O through a selectively permeable mb Aquaporins in plasma 12 Effect of Membrane Permeability on Diffusion and Osmosis: Diffusion of Solute 13 Effect of Membrane Permeability on Diffusion and Osmosis: Diffusion of Solvent Osmotic pressure vs. Hydrostatic pressure 14  Solutions: solute & solvent Tonicity Osmosis in – Isotonic (0.9% NaCl in Cells humans) – Hypotonic solution  Hemolysis – Hypertonic solution  Crenation 15  Facilitated Diffusion Through Membrane Channels Slower than diffusion through mb Important for nutrient absorption & waste excretion Nonpolar, hydrophobic molecules – Mb channel specific – Open or gated 16  Facilitated Diffusion Using a Carrier Protein Substances pass via carrier protein w/ concentration gradients – Conformational change in transporter – No energy input Rate of movement depends upon – steepness of concentration 17  Primary Active Transport Movement of polar or charged substances against concentration gradient – Requires energy input – Carrier molecule Ex: Na+/K+ ATPase Pump – Maintains osmotic pressure across mb 18 Na+/K+ Pump 1. Na+ binding 2. ATP split 3. Na+pushed out 4. K+ binding 5. Phosphate release 6. K+ is pushed in 19  Secondary Active Transport Energy stored in [ion] gradient to move other substances against their [ ] gradient Na +/K+ pump maintains steep concentration gradient of Na+ across plasma mb – Na+ antiporters – Na + symporters 20  Vesicular Transport - Exocytosis Exportation of cellular contents – Vesicles form inside cell  fuse w/ mb 21  Vesicular Transport- Endocytosis Phagocytosis = “cell eating” – WBC’s (macrophage) – Pseudopods form phagosome – Lysosome joins  phagolysosome --Digestion by enzymes 22  Vesicular Transport - Endocytosis Pinocyto sis = “cell drinking” – No receptor proteins – No pseudopods form 23  Vesicular Transport - Endocytosis Receptor-mediated endocytosis = selective input Clinical applications: – HIV virus – Familial Hypercholesteremia 24  Vesicular Transport - Transcytosis Endocytosis on one side of the cell Vesicle moves across cell Exocytosis on the other side of the Examples cell – Molecules, including some antibodies, move across placenta – Substances pass between blood and interstitial 25 (extracellular fluid) BRAIN 26 Passive Membrane Transport – Review Energy Process Source Example Simple diffusion Concentration Movement of O2 through mb Gradient Facilitated Concentration Movement of glc into cells diffusion Gradient Concentration Movement of H2O in & out of Osmosis Gradient cells 27  Active Membrane Transport – Review Energy Process Source Example -primary active transport ATP Movement of ions across mb -secondary active transport (Concentration Glucose symporter, H+ (symporters & antiporters) gradient) antiporter Exocytosis ATP Neurotransmitter secretion Endocytosis ATP WBC phagocytosis & pinocytosis Receptor-mediated Hormone & cholesterol endocytosis ATP uptake Transcytosis ATP Antibodies across palcenta 28  Clinical Application Pfizer and Moderna mRNA Covid-19 vaccines Use lipid coating similar to vesicle on outside of mRNA to gain entrance to our cells Process is similar to endocytosis 29 30 31  Cell Communication Direct Contact – Examples: Immune cells distinguish normal vs. foreign & destroy unhealthy or foreign cells Sperm & egg Regrowth of epidermis Ligand-Receptor Signaling- Examples: Neutrotransmitter in nervous system Hormones in endocrine system Cytokines in immune system 3 types: – Channel linked (chemically/ligand gated channels) – Enzymatic Receptors – G-protein coupled receptors 32  Cell Communication: Ligand-Receptor Signaling Channel-linked Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. receptors Ions Channel open – Permit ion passage into or out of cells Ligand – Occurs in response to neurotransmitter Channel closed binding – Help initiate electrical changes in muscle and nerve Ions cells (a) Channel-linked receptors  Cell Communication: Ligand-Receptor Signaling Enzymatic Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. receptors – Protein kinase enzymes Ligand – Activated to phosphorylate other enzymes within the cell Inactive Active protein protein kinase enzyme – Provides kinase phosphorylates enzyme mechanism for other enzymes. altering enzymatic Phosphate Enzyme turned activity on or turned off (b) Enzymatic receptors  Cell Communication: Ligand-Receptor Signaling G protein-coupled receptors – Indirectly activate protein kinase enzymes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 A ligand binds to a receptor, causing a Ions conformational change Ligand to activate receptor. Effector protein (e.g., ion channel) 2 G protein binds to activated Inactive protein receptor. kinase enzyme 5 Active protein kinase enzyme phosphorylates other Second enzymes messenger Activated G protein GTP 3 GTP binds to G protein 4 The activated effector protein Phosphate causing G protein activation. makessecondary messenger Activated G protein leaves the Effector protein available within the cell, which receptor. It attaches to and (e.g., enzyme) leads to protein kinase activates an effector protein. Enzyme turned enzyme activation. (an ion channel or an enzyme). on or turned off  Cytoplasm Two component s - 1) Cytosol - Intracellul ar fluid (ICF) - 2) Organelles 36  Cytosol Site of many important chemical rxns – production of ATP, synthesis of building blocks Contains large organic molecules small organic & inorganic molecules Inclusions organelles 37  Cell Organelles Specialized cellular compartments Membranous Non-membranous 38  Functions Cytoskeleton Network of protein filaments in cytosol 1. Microfilaments 2. Intermediate filaments 3. Microtubules Dynamic 41 Centrosome Found near nucleus Centrosome – Centriole 42  Cilia and Flagella Structure – microtubules covered by cell mb – basal body Differences – cilia – flagella 43  Ribosomes Packages of rRNA & protein 2 subunits 3 types – Free ribosomes – Inside mitochondria – Mb-bound ribosomes 44  Endoplasmic Reticulum Network of membranes Rough ER – synthesizes, processes & packages proteins for export Smooth ER – synthesizes phospholipids, steroids & fats – detoxifies harmful 45  Golgi Complex Processes & packages proteins produced by rough ER Cisterns Cis face Trans face 46 Processing & Packaging by Golgi Complex 47  Vacuoles & vesicles Vacuoles Vesicles Fxn in storage Single mb surrounding solid or liquid contents Variety of vacuoles 48  Lysosomes Membranous vesicle – Formed in Golgi complex – Filled w/ digestive enzymes – Internal pH 5.0 Functions – Digest foreign substances – Autophagy (autophagosome forms) 49  Lysosomes Clinical Applications – Tay Sachs Disease – Listeria monocytogenes infection 50  Peroxisomes Membranous vesicle – smaller than lysosomes – contains enzymes called oxidases & catalases Function – metabolic 51  Proteasomes Tiny barrel shaped structures – smaller than lysosomes & peroxisomes – contains enzymes called proteases Alzheimer’s and 52  Mitochondria Double mb organelle – Matrix – Cristae Function – ATP synthesis Mitochondria self- replicate – increase w/ need for ATP – maternal inheritance 53  Large Nucleus organelle w/ double mb nuclear envelope – Nuclear pores – Genetic material Nucleolus – Ribosomal proteins 54  Nucleus houses genetic material 46 human chromosomes – Genes Dividing cells contain chromosomes – tightly packed DNA – replicated before condensing Non-dividing cells contain nuclear chromatin – loosely packed DNA 55  Protein Synthesis Much of the cell’s machinery is devoted to synthesizing a wide variety of proteins Proteins determine the physical and chemical characteristics of cells, thus their function Types of proteins: – Assemble cellular structures – Secreted as antibodies, hormones, neutrotransmiters, other chemical messengers b/w cells – Receptors for molecules from our cells and foreign pathogens – Enzymes regulating chemical reactions – Contractile elements of muscles – Transporters in blood 56  Central Dogma Theory Flow of genetic information: Replication Replication  new DNA copies of DNA Transcription Transcription  RNA using DNA info RNA Nucleus Translation Translation  protein using Protein RNA info Cytoplasm 57  function mRNA Messenger RNA encodes protein (the message) rRNA Ribosomal RNA Types part of ribosome, used to translate mRNA into protein of RNA tRNA Transfer RNA couples the region which binds the mRNA codon & its amino acid 58 tRNA Structure 59 Nucleoti de Pairing DNA RNA –Guanin –Cytosine e –Guanine –Cytosin –Adenine e –Uracil – 60  Summary of Transcription & Translation Base Base Base triplet triplet triplet DNA DNA T T C A G T C A G template Transcription strand process A A G U C A G U C Messenger RNA mRNA Codon Codon Codon Translation anticodon anticodon anticodon process Transfer U U C A C U C A G RNA Polypeptide Protein Lysine Serine Valine (amino acid sequence) 61  mRNA & Transcription Carries genetic message Transcription: – Base triplets – Codons – RNA ploymerase – Promotor – Terminator – Pre-mRNA – Introns – Exons – snRNPs 62  Gene DNA Transcription Transcription 1 Initiation. DNA is unwound by enzymes to expose a Coding strand segment of a gene; RNA polymerase attaches to promoter region of the gene. Template strand RNA polymerase Promoter region RNA polymerase 2 Elongation. RNA polymerase assists with complementary base pairing of free ribonucleotides Coding strand with exposed bases of the template strand of DNA. Hydrogen bonds form between bases of DNA and the newly forming RNA molecule; this process continues as RNA Rewinding polymerase moves along the Hydrogen DNA strand. bonds DNA RNA (T) Thymine (A) Adenine (A) Adenine (U) Uracil Unwinding (C) Cytosine (G) Guanine Template strand (G) Guanine (C) Cytosine Ribonucleotide Exon Intron Intron Pre-mRNA strand Exon 3 Termination. RNA polymerase reaches the terminal region of the gene; newly formed RNA strand is released from the DNA strand. DNA finishes and rewinds into a double helix. Terminal region 63  Ribosomal RNA Structure 2 Subunits in each ribosome Physically supports structures involved in protein synthesis – Large subunit 64  Translation The process of reading sequence of mRNA & creating AA sequence of protein 65  Summary of Transcripti on & Translation 66 Genetic Engineering: Inserting Genes into the Genome (new pieces of DNA) 67  DNA sequence for GFP insertee into mouse genome = GFP expressing mice 68  Clinical Application Pfizer and Moderna mRNA Covid-19 vaccines mRNA from vaccine does NOT alter DNA mRNA gets translated into proteins Spike proteins, but NOT virus, get made 69 Altered Translation in Cell 70 Spike Proteins Initiate Immune Response – Make -T cells, -B cells & -Antibodies Against Proteins 71  DNA can be transcribed for the purpose of translation into proteins DNA is also replicated for the purpose of cellular division – increase the number of cells – reproduction 72  Normal Cell Division Mitosis - somatic cell division – parent cell  2 identical daughter cells Interphase = cell growth & DNA replication mitosis = nuclear division Prophase Metaphase Anaphase Telophase cytokinesis = cytoplasmic division – occurs in billions of cells/day – needed for tissue repair & growth Meiosis - reproductive cell division – egg & sperm cell production – in testes & ovary only 73  Interphase Stage of Cell Cycle Doubling of DNA & organelles Phases of interphase – G1 = replicate organelles & cytoplasm – S = replication of chromosomes – G2 = cytoplasmic growth – G0 = cell time out (some cells, such as neurons, are here permanently and thus never divide) 74 DNA Replication – Occurs During S Phase of Interphase 75  Mitosis: Prophase Chromatin condenses into chromosomes Nucleolus & nuclear envelope disappear Centrosomes move to opposite ends of cell – mitotic spindle forms w/ microtubules – spindle responsible for separation of chromatids 76  Mitosis: Metaphase Chromatid pairs line up across the middle of cell at the metaphase plate 77  Mitosis: Anaphase Chromatids (daughter chromosomes) move toward opposite poles of cell – movement due to shortening of microtubules Chromosomes appear V-shaped as they are dragged towards poles 78  Mitosis: Telophase Chromosomes stop moving Appear as dark, condensed bundle Chromosomes uncoil  chromatin Nucleoli & nuclear mb reappear Mitotic spindle breaks up 79  Cytokinesis Division of cytoplasm & organelles Begins in late anaphase w/ formation of cleavage furrow – indentation of mb by actin microfilaments Ends with 2 daughter cells in interphase 80 Overview : Cell Division 81 Overview: Cell Division 82  Control of Cell Destiny Cell destiny is either to: – remain alive & functioning – grow & divide – die Homeostasis maintains balance between cell multiplication & cell death – Cyclin builds up during interphase & triggers mitosis – Apoptosis occurs if a triggering agent turns on suicide enzymes that kills the cell – Necrosis is cell death caused by injury or infection 83 p53 Gene – “Tumor Suppressor Gene” Regulation of apoptosis during G1/S phase of interphase: – Normal p53 gene product present – damaged cells will be targeted for death – Mutant p53 – damaged cell may proceed through cell cycle and proliferate uncontrolled High % of human cancers linked to mutations of p53 84 How Elephants Avoid Cancer 85 October, 2015, Nature Cancer = out of control cell division Hyperplasia = increased # cell divisions – Benign - tumor does not metatasize or spread – Malignant - spreads due to cells that detach from tumor & enter blood or lymph – Causes – carcinogens (UV light, x-rays, chemicals such as those in cigarettes); viruses (HPV causes proteasomes to destroy p53, a protein that suppresses unregulated cell division) Carcinogenesis- Multistep process that 86  Apoptosis Programmed cell death is part of normal development 1. Death receptor on cell binds signal molecule 2. Enzymes destroy cell structures 3. Phagocytes engulf cell remnants Examples: chick embryo, webbed toes, autism 87  Necrosis Pathological type of cell death Results from lack of oxygen or tissue damage Tissue necrosis following bite from Bothrops asper (venomous snake) http://commons.wikimedia.org/wiki/Image 88  Aging Age alters the body’s ability to adapt to changes in the environment Theories to explain aging Evidence of aging – damaged skin, hardened arteries, stiff 89