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Cell - structural and functional unit of life -- smallest unit of life all living things made of cells cells come from cells Organismal functions depend on individual and collective cell functions Biochemical activities of cells dictated by their shapes or forms, and specific subcellular structures Continuity of life has cellular basis 1 Over 200 different types of human cells Types differ in size, shape, subcellular components, and functions 2 All cells have some common structures and functions Human cells have three basic parts: Plasma membrane—flexible outer boundary Cytoplasm—intracellular fluid containing organelles Nucleus—control center 3 Lipid bilayer and proteins in constantly changing fluid mosaic Plays dynamic role in cellular activity Separates intracellular fluid (ICF) from extracellular fluid (ECF) Interstitial fluid (IF) = ECF that surrounds cells 4 75% phospholipids (lipid bilayer) Phosphate heads: polar and hydrophilic Fatty acid tails: nonpolar and hydrophobic (Review Fig. 2.16b) 5% glycolipids Lipids with polar sugar groups on outer membrane surface 20% cholesterol Increases membrane stability 5 Allow communication with environment ½ mass of plasma membrane Most specialized membrane functions Some float freely Some tethered to intracellular structures Two types: Integral proteins; peripheral proteins 6 Integral proteins Firmly inserted into membrane (most are transmembrane) Have hydrophobic and hydrophilic regions Can interact with lipid tails and water Function as transport proteins (channels and carriers), enzymes, or receptors 7 Peripheral proteins Loosely attached to integral proteins Include filaments on intracellular surface for membrane support Function as enzymes; motor proteins for shape change during cell division and muscle contraction; cell-to-cell connections 8 1. Transport 2. Receptors for signal transduction 3. Attachment to cytoskeleton and extracellular matrix 9 10 11 12 13 14 ~20% of outer membrane surface Contain phospholipids, sphingolipids, and cholesterol More stable; less fluid than rest of membrane May function as stable platforms for cell-signaling molecules, membrane invagination, or other functions 15 "Sugar covering" at cell surface Lipids and proteins with attached carbohydrates (sugar groups) Every cell type has different pattern of sugars Specific biological markers for cell to cell recognition Allows immune system to recognize "self" and "non self" Cancerous cells change it continuously glyco = sugar -- calyx = shell 16 Some cells "free" e.g., blood cells, sperm cells Some bound into communities Three ways cells are bound: Tight junctions Desmosomes Gap junctions 17 Adjacent integral proteins fuse form impermeable junction encircling cell Prevent fluids and most molecules from moving between cells Where might these be useful in body? 18 "Rivets" or "spot-welds" that anchor cells together at plaques (thickenings on plasma membrane) Linker proteins between cells connect plaques Keratin filaments extend through cytosol to opposite plaque giving stability to cell Reduces possibility of tearing Where might these be useful in body? 19 Transmembrane proteins form pores (connexons) that allow small molecules to pass from cell to cell For spread of ions, simple sugars, and other small molecules between cardiac or smooth muscle cells 20 Cells surrounded by interstitial fluid (IF) Contains thousands of substances, e.g., amino acids, sugars, fatty acids, vitamins, hormones, salts, waste products Plasma membrane allows cell to Obtain from IF exactly what it needs, exactly when it is needed Keep out what it does not need 21 Plasma membranes selectively permeable Some molecules pass through easily; some do not Two ways substances cross membrane Passive processes Active processes Passive processes No cellular energy (ATP) required Substance moves down its concentration gradient Active processes Energy (ATP) required Occurs only in living cell membranes 22 Two types of passive transport Diffusion Simple diffusion Carrier- and channel-mediated facilitated diffusion Osmosis Filtration Usually across capillary walls 23 Collisions cause molecules to move down or with their concentration gradient Difference in concentration between two areas Speed influenced by molecule size and temperature 24 Molecule will passively diffuse through membrane if It is lipid soluble, or Small enough to pass through membrane channels, or Assisted by carrier molecule 25 Nonpolar lipid-soluble (hydrophobic) substances diffuse directly through phospholipid bilayer E.g., oxygen, carbon dioxide, fat-soluble vitamins 26 Certain lipophobic molecules (e.g., glucose, amino acids, and ions) transported passively by Binding to protein carriers Moving through water-filled channels 27 Transmembrane integral proteins are carriers Transport specific polar molecules (e.g., sugars and amino acids) too large for channels Binding of substrate causes shape change in carrier then passage across membrane Limited by number of carriers present Carriers saturated when all engaged 28 Aqueous channels formed by transmembrane proteins Selectively transport ions or water Two types: Leakage channels Always open Gated channels Controlled by chemical or electrical signals 29 Movement of solvent (e.g., water) across selectively permeable membrane Water diffuses through plasma membranes Through lipid bilayer Through specific water channels called aquaporins (AQPs) Occurs when water concentration different on the two sides of a membrane 30 Water concentration varies with number of solute particles because solute particles displace water molecules Osmolarity - Measure of total concentration of solute particles Water moves by osmosis until hydrostatic pressure (back pressure of water on membrane) and osmotic pressure (tendency of water to move into cell by osmosis) equalize 31 When solutions of different osmolarity are separated by membrane permeable to all molecules, both solutes and water cross membrane until equilibrium reached When solutions of different osmolarity are separated by membrane impermeable to solutes, osmosis occurs until equilibrium reached Osmosis causes cells to swell and shrink Change in cell volume disrupts cell function, especially in neurons 32 Tonicity: Ability of solution to alter cell's water volume Isotonic: Solution with same non-penetrating solute concentration as cytosol Hypertonic: Solution with higher non-penetrating solute concentration than cytosol Hypotonic: Solution with lower non-penetrating solute concentration than cytosol 33 Energy from solution (heat) = kinetic energy 34 Located between plasma membrane and nucleus Composed of Cytosol Water with solutes (protein, salts, sugars, etc.) Organelles Metabolic machinery of cell; each with specialized function; either membranous or nonmembranous Inclusions Vary with cell type; e.g., glycogen granules, pigments, lipid droplets, vacuoles, crystals 35 Membranous Membranes allow crucial compartmentalization Mitochondria Peroxisomes Lysosomes Endoplasmic reticulum Golgi apparatus Nonmembranous Cytoskeleton Centrioles Ribosomes 36 Double-membrane structure with inner shelflike cristae Provide most of cell's ATP via aerobic cellular respiration Requires oxygen Contain their own DNA, RNA, ribosomes Similar to bacteria; capable of cell division called fission 37 Granules containing protein and rRNA Site of protein synthesis Free ribosomes synthesize soluble proteins that function in cytosol or other organelles Membrane-bound ribosomes (forming rough ER) synthesize proteins to be incorporated into membranes, lysosomes, or exported from cell 38 Interconnected tubes and parallel membranes enclosing cisterns Continuous with outer nuclear membrane Two varieties: Rough ER Smooth ER 39 External surface studded with ribosomes Manufactures all secreted proteins Synthesizes membrane integral proteins and phospholipids Assembled proteins move to ER interior, enclosed in vesicle, go to Golgi apparatus 40 Network of tubules continuous with rough ER Its enzymes (integral proteins) function in Lipid metabolism; cholesterol and steroid-based hormone synthesis; making lipids of lipoproteins Absorption, synthesis, and transport of fats Detoxification of drugs, some pesticides, carcinogenic chemicals Converting glycogen to free glucose Storage and release of calcium 41 Stacked and flattened membranous sacs Modifies, concentrates, and packages proteins and lipids from rough ER Transport vessels from ER fuse with convex cis face; proteins modified, tagged for delivery, sorted, packaged in vesicles 42 Three types of vesicles bud from concave trans face Secretory vesicles (granules) To trans face; release export proteins by exocytosis Vesicles of lipids and transmembrane proteins for plasma membrane or organelles Lysosomes containing digestive enzymes; remain in cell 43 Membranous sacs containing powerful oxidases and catalases Detoxify harmful or toxic substances Catalysis and synthesis of fatty acids Neutralize dangerous free radicals (highly reactive chemicals with unpaired electrons) Oxidases convert to H2O2 (also toxic) Catalases convert H2O2 to water and oxygen 45 Spherical membranous bags containing digestive enzymes (acid hydrolases) "Safe" sites for intracellular digestion Digest ingested bacteria, viruses, and toxins Degrade nonfunctional organelles Metabolic functions, e.g., break 46 down and release glycogen Destroy cells in injured or nonuseful tissue (autolysis) Break down bone to release Ca2+ 46 Overall function Produce, degrade, store, and export biological molecules Degrade potentially harmful substances Includes ER, Golgi apparatus, secretory vesicles, lysosomes, nuclear and plasma membranes 47 Elaborate series of rods throughout cytosol; proteins link rods to other cell structures Three types Microfilaments Intermediate filaments Microtubules 48 Thinnest of cytoskeletal elements Dynamic strands of protein actin Each cell has a unique arrangement of strands Dense web attached to cytoplasmic side of plasma membrane is called terminal web Gives strength, compression resistance Involved in cell motility, change in shape, endocytosis and exocytosis 49 Tough, insoluble, ropelike protein fibers Composed of tetramer fibrils Resist pulling forces on cell; attach to desmosomes E.g., neurofilaments in nerve cells; keratin filaments in epithelial cells 50 Largest of cytoskeletal elements; dynamic hollow tubes; most radiate from centrosome Composed of protein subunits called tubulins Determine overall shape of cell and distribution of organelles Mitochondria, lysosomes, secretory vesicles attach to microtubules; moved throughout cell by motor proteins 51 Protein complexes that function in motility (e.g., movement of organelles and contraction) Powered by ATP 52 "Cell center" near nucleus Generates microtubules; organizes mitotic spindle Contains paired centrioles Barrel-shaped organelles formed by microtubules Centrioles form basis of cilia and flagella 53 The paired centrioles that are the centrosome make up one of the microtubule organizing centers (MTOC) of the cell. 54 Cilia and flagella Whiplike, motile extensions on surfaces of certain cells Contain microtubules and motor molecules Cilia move substances across cell surfaces Longer flagella propel whole cells (tail of sperm) 55 Centrioles forming base called basal bodies Cilia movements alternate between power stroke and recovery stroke current at cell surface Primary cilia Single, nonmotile projection on most cells Probe environment for molecules receptors can recognize; coordinate intracellular pathways 56 Microvilli Minute, fingerlike extensions of plasma membrane Increase surface area for absorption Core of actin filaments for stiffening 57 Largest organelle; genetic library with blueprints for nearly all cellular proteins Responds to signals; dictates kinds and amounts of proteins synthesized Most cells uninucleate; skeletal muscle cells, bone destruction cells, and some liver cells are multinucleate; red blood cells are anucleate Three regions/structures 58 Double-membrane barrier; encloses nucleoplasm Outer layer continuous with rough ER and bears ribosomes Inner lining (nuclear lamina) maintains shape of nucleus; scaffold to organize DNA Pores allow substances to pass; nuclear pore complex line pores; regulates transport of large molecules into and out of nucleus 59 Dark-staining spherical bodies within nucleus Involved in rRNA synthesis and ribosome subunit assembly Associated with nucleolar organizer regions Contains DNA coding for rRNA Usually one or two per cell 60 Threadlike strands of DNA (30%), histone proteins (60%), and RNA (10%) Arranged in fundamental units called nucleosomes Histones pack long DNA molecules; involved in gene regulation Condense into barlike bodies called chromosomes when cell starts to divide 61 Defines changes from formation of cell until it reproduces Includes: Interphase Cell grows and carries out functions Cell division (mitotic phase) Divides into two cells Period from cell formation to cell division Nuclear material called chromatin Three subphases: G1 (gap 1)—vigorous growth and metabolism Cells that permanently cease dividing said to be in G0 phase S (synthetic)—DNA replication occurs G2 (gap 2)—preparation for division Prior to division cell makes copy of DNA DNA helices separated into replication bubbles with replication forks at each end Each strand acts as template for complementary strand DNA polymerase begins adding nucleotides at RNA primer DNA polymerase continues from primer Synthesizes one leading, one lagging strand DNA polymerase only works in one direction Leading strand synthesized continuously Lagging strand synthesized discontinuously into segments DNA ligase splices short segments of discontinuous strand together End result: two identical DNA molecules formed from original During mitotic cell division one complete copy given to new cell; one retained in original cell Process is called semiconservative replication Each DNA composed of one old and one new strand Meiosis - cell division producing gametes Mitotic cell division - produces clones Essential for body growth and tissue repair Occurs continuously in some cells •Skin; intestinal lining None in most mature cells of nervous tissue, skeletal muscle, and cardiac muscle Repairs with fibrous tissue Mitosis—division of nucleus Four stages ensure each cell receives copy of replicated DNA Prophase Metaphase Anaphase Telophase Cytokinesis—division of cytoplasm by cleavage furrow Chromosomes become visible, each with two chromatids joined at centromere Centrosomes separate and migrate toward opposite poles Mitotic spindles and asters form Nuclear envelope fragments Kinetochore microtubules attach to kinetochore of centromeres and draw them toward equator of cell Polar microtubules assist in forcing poles apart Centromeres of chromosomes aligned at equator Plane midway between poles called metaphase plate Shortest phase Centromeres of chromosomes split simultaneously—each chromatid becomes a chromosome Chromosomes (V shaped) pulled toward poles by motor proteins of kinetochores Polar microtubules continue forcing poles apart Begins when chromosome movement stops Two sets of chromosomes uncoil to form chromatin New nuclear membrane forms around each chromatin mass Nucleoli reappear Spindle disappears Begins during late anaphase Ring of actin microfilaments contracts to form cleavage furrow Two daughter cells pinched apart, each containing nucleus identical to original "Go" signals: Critical volume of cell when area of membrane inadequate for exchange Chemicals (e.g., growth factors, hormones) Availability of space–contact inhibition To replicate DNA and enter mitosis requires Cyclins–regulatory proteins Accumulate during interphase Cdks (Cyclin-dependent kinases)–bind to cyclins activated Enzyme cascades prepare cell for division Cyclins destroyed after mitotic cell division "Go" signals G1 checkpoints (restriction point) most important If doesn't pass G0–no further division Late in G2 MPF (M-phase promoting factor) required to enter M phase "Other Controls" signals Repressor genes inhibit cell division E.g., P53 gene 78 DNA is master blueprint for protein synthesis Gene - segment of DNA with blueprint for one polypeptide. (In other words, a specific location on the DNA molecule.) Triplets (three sequential DNA nitrogen bases) form genetic library Bases in DNA are A, G, T, and C Each triplet specifies coding for number, kind, and order of amino acids in polypeptide 80 Genes composed of exons and introns Exons code for amino acids Introns–noncoding segments Role of RNA DNA decoding mechanism and messenger Three types–all formed on DNA in nucleus Messenger RNA (mRNA); ribosomal RNA (rRNA); transfer RNA (tRNA) RNA differs from DNA Uracil is substituted for thymine Messenger RNA (mRNA) Carries instructions for building a polypeptide, from gene in DNA to ribosomes in cytoplasm Ribosomal RNA (rRNA) Structural component of ribosomes that, along with tRNA, helps translate message from mRNA Transfer RNAs (tRNAs) Bind to amino acids and pair with bases of codons of mRNA at ribosome to begin process of protein synthesis Transcription = DNA into RNA Translation = RNA in protein Transfers DNA gene base sequence to complementary base sequence of mRNA Transcription factors–gene activators Loosen histones from DNA in area to be transcribed Bind to promoter-DNA sequence specifying start site of gene on template strand Mediate binding of RNA polymerase (enzyme synthesizing mRNA) to promoter Three phases Initiation RNA polymerase separates DNA strands Elongation RNA polymerase adds complementary nucleotides Termination Termination signal indicates "stop" Transcription factors–gene activators Loosen histones from DNA in area to be transcribed Bind to promoter-DNA sequence specifying start site of gene on template strand Mediate binding of RNA polymerase (enzyme synthesizing mRNA) to promoter Initiation RNA polymerase separates DNA strands Elongation RNA polymerase adds complementary nucleotides Termination Termination signal indicates "stop" mRNA edited and processed before translation Introns removed by spliceosomes mRNA complex proteins associate to guide export, ensure accuracy for translation Converts base sequence of nucleic acids into amino acid sequence of proteins Involves mRNAs, tRNAs, and rRNAs Each three-base sequence on DNA (triplet) represented by codon Codon—complementary three-base sequence on mRNA Some amino acids represented by more than one codon 45 different types Binds specific amino acid at one end (stem) Anticodon at other end (head) binds mRNA codon at ribosome by hydrogen bonds E.g., if codon = AUA, anticodon = UAU Ribosome coordinates coupling of mRNA and tRNA; contains three sites Aminoacyl site; peptidyl site; exit site Translation is the process in which genetic information carried by an mRNA is decoded in the ribosome to form a particular polypeptide. Three phases that require ATP, protein factors, and enzymes Initiation Elongation Termination Small ribosomal subunit binds to initiator tRNA and mRNA to be decoded; scans for start codon Large and small ribosomal units attach, forming functional ribosome At end of initiation tRNA in P site; A site vacant New amino acids added by other tRNAs as ribosome moves along mRNA Initial portion of mRNA can be "read" by additional ribosomes Polyribosome multiple ribosome-mRNA complex Produces multiple copies of same protein Three steps Codon recognition tRNA binds complementary codon in A site Peptide bond formation Amino acid of tRNA in P site bonded to amino acid of tRNA in A site Translocation tRNAs move one position–A P; P E When stop codon (UGA, UAA, UAG) enters A site Signals end of translation Protein release factor binds to stop codon water added to chain release of polypeptide chain; separation of ribosome subunits; degradation of mRNA Protein processed into functional 3-D structure mRNA–ribosome complex directed to rough ER by signal-recognition particle (SRP) Forming protein enters ER Sugar groups may be added to protein, and its shape may be altered Protein enclosed in vesicle for transport to Golgi apparatus Complementary base pairing directs transfer of genetic information in DNA into amino acid sequence of protein DNA triplets mRNA codons Complementary base pairing of mRNA codons with tRNA anticodons ensures correct amino acid sequence Anticodon sequence identical to DNA sequence except uracil substituted for thymine Intron ("junk") regions of DNA code for other types of RNA: Antisense RNA Prevents protein-coding RNA from being translated MicroRNA Small RNAs that silence mRNAs made by certain exons Riboswitches Folded RNAs that act as switches regulating protein synthesis in response to environmental conditions Autophagy Cytoplasmic bits and nonfunctional organelles put into autophagosomes; degraded by lysosomes Ubiquitins Tag damaged or unneeded soluble proteins in cytosol Digested by soluble enzymes or proteasomes All cells of body contain same DNA but cells not identical Chemical signals in embryo channel cells into specific developmental pathways by turning some genes on and others off Development of specific and distinctive features in cells called cell differentiation During development more cells than needed produced (e.g., in nervous system) Eliminated later by programmed cell death (apoptosis) Mitochondrial membranes leak chemicals that activate caspases DNA, cytoskeleton degradation cell death Dead cell shrinks and is phagocytized Organs well formed and functional before birth Cell division in adults to replace short-lived cells and repair wounds Hyperplasia increases cell numbers when needed Atrophy (decreased size) results from loss of stimulation or use