Kine 2011 Module 1 Lecture Notes 1-10 PDF

lOMoARcPSD|39194630 Kine 2011 Module 1 - Lecture notes 1-10 Physiology 1 (York University) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by Sandra Salama...

lOMoARcPSD|39194630 Kine 2011 Module 1 - Lecture notes 1-10 Physiology 1 (York University) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 1 Kine 2011 Module 1: Dr Abdul-Sater Lecture 1: Cell Physiology Friday, September 7, 2018 Principles of Cell Theory Cell = smallest structural and functional unit to carry out life processes o Cell Theory → Theodor Schwann Functional properties of cell depend on structural properties Cells = building blocks of animals and plants Cells = basic unit of life Organism structure and function depend on functional and structural characteristics and functional capabilities of cell Because of this continuity in life, cells of all organisms are fundamentally similar Cell Structure and Function 200 cell types (muscle, nerve, skin) o Based on specific variations in structure and function o Common features = ▪ Plasma membrane → block things out/regulate ▪ Cytosol → everything inside the cell (organelles) ▪ Nucleus → controls everything PLASMA MEMBRANE o Thin membranous structure that encloses the cell o Composed mostly of bilayer of lipid o Studded with proteins o Separates cell contents from surroundings o Selective control of movement of molecules in + out of the cell NUCLEUS o Surrounded by double layered membrane ▪ Has pores that allow proteins + nucleic acids in o Houses genetic info → DNA o Genetic blueprint during cell replication o Directs protein synthesis ENDOPLASMIC RETICULUM o Fluid filled membranous system o Protein + lipid producing o Rough ER ▪ Studded with ribosomes ▪ Synthesis protein to be secreted to the exterior or to be incorporated into plasma membrane or other cell composition o Smooth ER ▪ Packages the secretory product into transport vesicles which bud off and move to the Golgi complex ▪ Lipid synthesis Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 2 GOLGI COMPLEX o Stacks of flat/slightly curved membrane enclosed sacs o Closely associated with ER o Modifies packages and distributes newly synthesized proteins o Puts in specific vesicle to send to specific place LYSOSOMES o Small membrane enclosed organelles o Break down organic molecules with hydraulic enzyme ▪ Breaks down peptide bonds using water o Digestive system of cell: destroys foreign substances + cellular debris PEROXISOMES o Membrane enclosed sacs containing oxidative enzymes o Detoxify various wastes produced within cells or foreign toxic compounds that have entered cell ▪ Ex. Alcohol o Liver has the most MITOCHONDRIA o Rod or oval shaped about size of bacteria o Enclosed by double membrane o Inner membrane forms series of infoldings called cristae o Cristae project into inner cavity filled with gel-like solution called matrix o Spaces between cristae + matrix = intermembrane space o Energy organelles or “power plants” of the cell o Extract energy from the nutrients in food and transform into ATP o Contains enzymes for Citric Acid Cycle (TCA) and Electron Transport Chain CENTRIOLES o Pair of cylindrical structures at right angles to each other o Form and organize microtubules during assembly of the mitotic spindle during cell division o Form cilia and flagella VAULTS o Hollow octagonal barrels o Serve as cellular trucks for transport from nucleus to cytoplasm Lecture 2: Cell Physiology Monday, September 10, 2018 Cytoskeleton M ICROTUBULES o Long, slender, hollow tubes composed of tubulin molecule o Maintain asymmetrical cell shapes and coordinate complex cell movement (not muscle contraction, movement of organelles, proteins) ▪ Highways for transport of secretory vesicles within cell o Main structural and functional component of cilia and flagella o Position cytoplasmic organelles (ER, Golgi Complex, etc…) o Assemble into mitotic spindle o Ex. Neuron transmitters sending signals MICROFILAMENTS o Smallest element Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 3 o Intertwined helical chains of actin molecules (in all cell types) o Myosin cells also present in muscle cells o Vital role in cellular contractile systems → muscle contraction + amoeboid movement (WBC + fibroblast) o Serve as mechanical stiffener for microvilli INTERMEDIATE FILAMENTS o Irregular thread like filaments/protein o Help resist mechanical stress o Need multiple together not just one = stronger o Ex. Keratin in hair Cytosol Cell gel INTERMEDIARY METABOLISM ENZYMES o Dispersed within the cytosol o Facilitate intracellular reactions involving degradation, synthesis, and transformation of small organic molecules TRANSPORT, SECRETORY, AND ENDOCYTIC VESICLES o Transiently formed, membrane-enclosed products synthesized within or engulfed by the cell o Transport or store products being moved within, out of, or into the cell, respectively INCLUSIONS o Glycogen granules, fat droplets o Store excess nutrients Cellular Metabolism I NTERMEDIARY METABOLI SM o Refers to large set of chemical reactions inside the cell that involves the degradation, synthesis and transformation of small organic molecules such as simple sugars, amino acids and fatty acids Energy The IM occurs in the cytosol and involves thousands of enzymes Anabolic Processes degradation synthesis providing the raw breakdown buildup Catabolic Processes materials to maintain used for cell activities the cells structure + function ATP o The source of energy for the body is the chemical energy stored in the carbon bonds of ingested food ▪ Must be extracted by the cell machinery and converted into a source of energy usable by the cell = high energy phosphate bonds of ATP (Adenosine TriPhosphate) o Bodies common energy “currency” ▪ Cells “cash in” ATP to pay the energy “price” for maintaining structure, function, growth o HOW IS ATP PRODUCED IN THE CELL? ▪ Creatine Phosphate (CP) ▪ Anaerobic Glycolysis ▪ Aerobic Metabolism ▪ Most ATP production → glycolysis (anaerobic + aerobic), decarboxylation of pyruvate, the tricarboxylic cycle (TCA), the electron transport chain Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 4 Creatine Phosphate SUBSTRATE-LEVEL PHOSPHORYLATION: THE CREATINE PHOSPHATE SYSTEM o Substrate- level phosphorylation of ADP using creatine phosphate o CP= first source of energy during muscle contractile activity o Stored in the cytoplasm o Like ATP, CP contains high energy phosphate bonds o Enzymatic reaction catalyzed by the creatine kinase ▪ Reaction = reversible o CP + ADP creatine kinase Creatine + ATP o At rest in the skeleton muscle : 5X more CP than ATP ▪ Most stored energy is in the form of CP o Skeletal muscle contraction: CP will replenish the used ATP. CP levels change faster than that of ATP o Only one enzymatic reaction: RAPID process Lecture 3: Cell Physiology Wednesday, September 12, 2018 Cellular Metabolism: Respiration GLYCOLYSIS o A chemical process involving 10 sequential reactions that break down glucose (6 carbon molecules) into two pyruvates (3 carbon molecules) o Some energy from broken chemical bonds of glucose is used directly to convert ADP into ATP (2 ATP) o Numerous metabolic diseases affect glycolysis ▪ McArdle Disease: absence of enzyme involved in the first step of glycogen to glucose conversion o Glycolysis is not very efficient in terms of energy extraction, only producing 2 ATP and 2 NADH per molecule of glucose (anaerobic). Most of the energy contained in the glucose molecule remains “locked” in the chemical bonds PYRUVATE DECARBOXYLATION o Pyruvate enters mitochondrial matrix o Catalyzed into Acetyl CoA (2 carbon molecule) CITRIC ACID CYCLE (TRICARBOXYLIC ACID CYCLE) o 8 separate reactions directed by enzymes from the mitochondrial matrix o Two carbon (2C) are sequentially removed from the 6C citrate molecule → converted back to the 4C oxaloacetate, ready to accept a new Acetyl CoA o These 2C are converted into 2 molecules of CO2 o These CO2 as well as the one produced during the pyruvate decarboxylation, pass out of the mitochondrial matrix → out of the cell → blood o The O2 used to form these CO2 molecules is coming from these molecules involved in the cycle, not from the free O2 supplied from breathing o Hydrogen atoms are also removed (four steps). This is the key part of the citric acid cycle! These H will then enter the Electron Transport Chain (ETC) o Hydrogen carrier molecules: NAD+ and FAD → NADH and FADH2 Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 5 o One ATP molecule is indirectly produced. The processing of ACoA releases energy → linkage of inorganic phosphate to GDP → GTP ▪ ADP + GTP ------→ ATP + GDP o One glucose → 2 Acetyl CoA → 2 turns of CTAC → 2 ATP o ** However, crucial step in getting NADH and FADH2 to enter ETC = limited energy profit ELECTRON TRANSPORT CHAIN (ETC) o Most of the energy is still stored in H (they contain electrons at high energy levels) o Series of electron carrier molecules on inner membrane of mitochondria o Electrons extracted from NADH and FADH2 o Most energy produced (ATP) o Ultimately electrons passed to O2 (final electron acceptor) o This process is called Oxidative Phosphorylation o NADH and FADH2 are then converted back into NAD+ and FAD ▪ Free to pick up new H molecules ▪ They represent the link between CTAC and ETC o 1 NADH → 2-3 ATP (2.5 ATP on average) o 1 FADH2 → 1-2 ATP (1.5 ATP on average) o The high energy electrons fall to successively lower energy levels as they are transferred from carrier to carrier through ETC o As electrons move through the electron transport system, they release free energy. Part of the released energy is harnessed to transport H+ from the matrix into intermembrane space at complexes I, III, and IV o As a result, H+ ions are more heavily concentrated in the intermembrane space than in the matrix. This H+ gradient supplies the energy that drives ATP synthesis by ATP synthase Lecture 4: Cell Physiology Friday, September 14, 2018 Cellular Metabolism This is under AEROBIC conditions If oxygen is limited or unavailable, pyruvate is not converted into ACoA but into lactate instead o Called ANAEROBIC condition Degradation of glucose does not proceed beyond glycolysis Much more energy produced by aerobic pathways Fatty acids and proteins (if necessary) can also be a source of ATP productions enter at Acetyl CoA step The Plasma Membrane Also called the cell membrane Surrounds every cell Extremely thin bilayer composed of proteins and lipids (some carbs) Separates the extracellular and intracellular compartments/fluids (ECF and ICF) Controls movements of molecules into and out of cell (not only a mechanical barrier) Active role in determining the composition of the cell by selectively permitting the movement of various molecules (ions, nutrients, secretory, and waste products etc.) Key in cell- cell and cell- with- its environment communication STRUCTURE AND COMPOSITION o The most abundant membrane lipids are phospholipids (PL) (and some cholesterol) Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 6 o ~ 1 billion PL molecules are present in the plasma membrane of a typical human cell o PL have a polar (hydrophilic) head and two nonpolar (hydrophobic) fatty acid chain tails o PL self- assemble into a lipid bilayer = double layer of lipid molecule ▪ Fluid (not rigid): consistency more like cooking oil than stick of butter. PL are constantly moving= twirl, vibrate and move around within their half of the bilayer, exchanging places millions/sec. ▪ Cholesterol also contributes to the fluidity and stability of the membrane. Intercalated in between the PL molecules o FLUID MOSAIC MODEL ▪ Mostly lipid, proteins and some carbohydrates ▪ The fluid mosaic model refers to membrane fluidity and the ever-changing mosaic patter of the proteins embedded in the lipid bilayer ▪ The fluidity of the lipid bilayer enables many membrane proteins to float freely like “icebergs” in the moving “sea” of lipids o MEMBRANE PROTEINS ▪ Channels (for small enough [ < 0.8m] water soluble molecules, such as small ions); selective (e.g. Na+ channel) ▪ Carrier molecules (transfer of specific substances; glucose) ▪ Docking- marker acceptors (for secretory vesicles and exocytosis process) ▪ Membrane- bound enzymes ▪ Receptors ▪ Cell adhesion molecules (CAMS) ▪ Peripheral proteins Lecture 5: Cell Physiology Monday, September 17, 2018 Cell-to-Cell Adhesions Plasma membranes also participate in cell-to-cell adhesions Cells are held together by three different means: o Cell Adhesion Molecules (CAMs) ▪ Ex. Velcro ▪ 3 types: Cadherins CAMS (sub group) Integrins o The Extracellular Matrix (ECM) o Specialized cell junctions EXTRACELLULAR MATRIX o The ECM is an intricate meshwork of fibrous proteins embedded in a watery gel-like substance (fluid in between tissue) (aka interstitial fluid) composed of complex carbohydrates ▪ Interstitial fluid = provides a pathway for diffusion of nutrients, wastes and other water-soluble traffic between the blood and tissue cells o Three major types of protein fibers woven through the gel are: ▪ Collagen: forms cable like fibers → tensile strength (most abundant protein in the body! ~ ½ of total body protein by weight) ▪ Elastin: rubber-like protein fiber → stretching and recoiling (e.g. in lungs) Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 7 ▪ Fibronectin: promotes cell adhesion → holds cell in position (reduced levels are linked to tumor metastasis) o Serves as biological glue for cells o Scant in epithelial tissue; abundant in connective tissue → secreted by fibroblasts SPECIALIZED CELL JUNCTIONS o CAMs provide some tissue cohesion as they “Velcro” adjacent cells together o Cells are directly linked by one of three types of specialized cell junctions: ▪ Desmosomes (adhering junctions) ▪ Tight junctions (impermeable junctions) ▪ Gap junctions (communicating junctions) o Desmosomes ▪ Act like “spot rivets” that anchor together two adjacent but non-touching cells ▪ Most abundant in tissues that are subject to considerable stretching (skin, heart, uterus) ▪ They are the strongest cell-to-cell connections o Tight Junctions ▪ Adjacent cells firmly bind together at points of contact to seal off the passageway between the two cells ▪ Found primarily in sheets of epithelial tissue such as those that cover the body and line internal cavities E.g. epithelial sheet lining the digestive tract separates the food and potent digestive juices within the inner cavity (lumen) from the blood vessels on the other side ▪ Impermeable barrier o Gap Junctions ▪ A gap exists between adjacent cells, which are linked by small, connecting tunnels (formed by connexons) ▪ Communicating junctions (permits small, water-soluble particles to pass between the connected cells but precludes passage of large molecules) ▪ Abundant in cardiac muscle and smooth muscle (allow movement of ions to transmit electrical activity → synchronized contraction of a whole muscle mass) Membrane Transport Notions of membrane permeability, membrane impermeability and selective permeability Two properties influence whether a substance can permeate the plasma membrane without any assistance: o Relative solubility of the particle in lipid ▪ Uncharged or non-polar molecules (O2, CO2, fatty acids) → highly lipid soluble → easy to permeate the plasma membrane ▪ Charged or polar molecules: ions, proteins and glucose → low lipid solubility and very soluble in water ▪ Size of particle Going through the membrane (lipid-soluble) or through a channel requires forces to induce the movement Forces that require the cell to expend energy → active forces Those that do not require the cell to spend energy → passive forces Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 8 Lecture 6: Cell Physiology Wednesday, September 19, 2018 Membrane Transport UNASSISTED MEMBRANE TRANSPORT o Molecules that can penetrate the plasma membrane on their own → passively driven across the membrane by two forces: ▪ Diffusion down a concentration gradient ▪ Movement along an electrical gradient 1. Passive Diffusion of Particles o Molecules are in continuous random motion o Tend to become evenly distributed over time (i.e. steady state or equilibrium) o Known as diffusion o Concentration gradient (chemical) o Net diffusion PASSIVE DIFFUSION AND PLASMA MEMBRANE o Net diffusion and movement of molecules down the concentration gradient (from high to low concentrations) ▪ Passive mechanism ▪ No energy required ▪ Example: oxygen transport across lung membrane FICK’S LAW OF DIFFUSION o The collective influence of factors on the rate of net diffusion of a substance across a membrane ▪ The magnitude (or steepness) of the concentration gradient ▪ The surface area of the membrane across which diffusion is taking place ▪ The lipid solubility of the substance ▪ The molecular weight of the substance ▪ The distance through which diffusion must take place 2. Passive Diffusion of Ions o Ions are electrically charged: in addition to concentration gradients (chemical), their movement is affected by their electrical charge o Ions with like charges repel each other, whereas those with opposite charges attract each other (positively charged = cations, negatively charged = anions) o A difference in charge b/w 2 adjacent areas thus produces an electrical gradient o The combinatorial effect of the concentration and electrical gradients on the ions forms the electrochemical gradients o ** these gradients, for a given ion, can be working in the same direction or in opposing directions 3. Osmosis o Water can readily permeate the plasma membrane ▪ Can slip b/w the PL molecules ▪ Or through specific water channels called Aquaporins (up to one billion molecules/sec) o Driving force is the concentration gradient o Net diffusion of water is known as osmosis Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 9 o “concentration” usually refers to the density of a solute (dissolved substance) in a given volume of water. Adding a solute to pure water decreases the water concentration. In general, one molecule of solute displaces one of molecule of water o Osmosis: movement of water when a selectively permeable membrane separates two unequal solute concentrations (unequal water concentration) ▪ Water molecules will move passively from high water concentration (low solute concentration) towards low water concentration (high solute concentration) ▪ The net diffusion of water is OSMOSIS Lecture 7: Cell Physiology Friday, September 21, 2018 Membrane Transport UNASSISTED MEMBRANE TRANSPORT o Tonicity = the effect the solution has on cell volume ▪ Tonicity of the solution is determined by the concentration of the solution in non-penetrating solutes (the penetrating ones are rapidly equally distributed b/w ECF and ICF ▪ Isotonic solutions: result in a constant cell volume ▪ Hypotonic solutions: tend to swell the cell ▪ Hypertonic solutions: tend to shrink the cell o Osmolarity = the measure of solute concentration per unit of solvent ▪ Osmolarity takes into account all of the solute concentrations (penetrating and nonpenetrating solutes) ▪ Iso-osmotic, hypo-osmotic, hyper-osmotic o Ion forming compounds: osmolarity > solutions molarity o Osmolarity (osmol/L) involved total amount of solutes present o Molarity (mol/L) involves concentration of the compound as a whole o For instance: NaCl once dissolved in water separates into its ions as Na+ and Cl- ▪ If NaCl concentration is 200 mmol/L (mM) at the start → upon the dissolution in water → molarity remains 200 mM but osmolarity increases to 400 mo smol/L. We have to consider the total number solutes in solution (i.e. the separated ions: 200 mosmol/L of Na+ and 200 mosmol/L of Cl-) Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 10 ASSISTED MEMBRANE TRANSPORT o Large poorly lipid-soluble molecules cannot cross the plasma membrane on their own (some of these molecules are essential nutrients e.g. glucose ) ▪ 2 different mechanisms: Carrier mediated transport (for small water soluble molecules) Vesicular transport (large molecules and multi-molecular particles) CARRIER MEDIATED TRANSPORT o Carrier proteins span the plasma membrane o They can reverse shape so binding sites are alternately exposed to the ECF and ICF (flip flops) ▪ 3 important characteristics: Specificity (amino acids cannot bind to glucose carriers) Saturation (limited number of carrier binding sites) Competition (closely related compounds compete for access) o TWO FORMS: ACTIVE OR PASSIVE TRANSPORT ▪ Facilitated diffusion: uses a carrier molecule to facilitate (assist) the transfer of a substance across the membrane from high to low concentration (downhill) Passive process (does not require energy) Occurs naturally down a concentration gradient Rate is limited by saturation of the carrier binding sites e.g. glucose is transported into the cells from the blood stream via GLUTs Comparison of carrier-mediated transport and simple diffusion down a concentration gradient (remember that carrier-mediated transport is characterized by 3 important parameters, includi ng competition) Lecture 8: Cell Physiology Monday, September 24, 2018 Membrane Transport- Assisted Membrane Transport CARRIER-MEDIATED TRANSPORT- TWO FORMS: ACTIVE OR PASSIVE TRANSPORT o ACTIVE TRANSPORT ▪ Also requires a carrier protein ▪ Expends energy ▪ Transfer its passengers “uphill” against a concentration gradient Car on a hill, moving downhill vs uphill o Primary Active Transport ▪ Energy (ATP) is directly required to move a substance against its concentration gradient ▪ Carriers binding sites have a greater affinity for the passenger ion on the low concentration side where the ion is picked up and lower affinity on the high concentration side where the ion is dropped off ▪ These carriers are often called pumps (act as enzymes with ATPase activity) ▪ Two types that always transport ions: Single type of passenger (i.e. H+ pump or Ca2+ pump) Na+-K+ pump involves the transfer of two different substances either simultaneously in the same direction or sequentially in opposite directions ▪ A single nerve cell membrane contains ~ 1 million Na+-K+ pumps capable of transporting ~200 million ions per second Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 11 ▪ Establishes Na+ and K+ concentration gradients across plasma membrane ▪ Also indirectly serves as the energy source for secondary active transport o Secondary Active Transport ▪ Energy is required in the entire process but is not directly required to run the pump (NO ATP is used directly by pump) ▪ Uses “second-hand” energy stored in the form of an ion (e.g. Na+) concentration gradient to move the co-transported molecule uphill ▪ Two Types: Symport (also called cotransport) the solute and Na+ move through the membrane in the same direction Antiport (also called counter-transport) the solute and Na+ move through the membrane in opposite directions ▪ E.g. movement of glucose against concentration gradient in intestinal kidney cells Lecture 9: Cell Physiology Wednesday, September 26, 2018 Membrane Transport: Assisted Membrane Transport VESICULAR TRANSPORT o For large polar molecules (e.g. protein hormones secreted by endocrine cells) and multi-molecular materials (e.g. bacteria ingested by white blood cells) to enter and leave the cell o Requires energy expenditure by the cell → active mechanism of transport ▪ This energy is needed to accomplish vesicle formation and movement within the cell o 2 FORMS OF ACTIVE TRANSPORT: ▪ Endocytosis: 3 forms depending on the material internalized Pinocytosis Fuses with lysosomes (rare Receptor-Mediated Endocytosis instances → bypasses lysosomes → Phagocytosis exocytosis from other end ▪ Exocytosis E NDOCYTOSIS o Pinocytosis (non-selective uptake sample of ECF) = “cell drinking” ▪ Micropinocytosis = large gulps of fluid (this is how dendritic cells take up foreign material to activate the immune system) o Receptor-Mediated Endocytosis (selective intake of a large molecule) ▪ Ex. Insulin, iron, vit. B12 uptake… but so does flu and HIV o Phagocytosis (selective uptake of a multimolecular molecule = “cell eating” ▪ Unlike pinocytosis and receptor mediated endocytosis, only certain specialized cells can perform phagocytosis → phagocytosis ▪ In immune responses, phagocytosis can be enhanced by receptors binding coated pathogens EXOCYTOSIS o Almost the reverse of endocytosis (NO fusion with lysosomes) o Two purposes: ▪ Secretion of large polar molecules (i.e. hormones or organism) Downloaded by Sandra Salama ([email protected])  lOMoARcPSD|39194630 Page 12 ▪ Addition of components to membrane (i.e. channels or receptors) o Exocytosis and secretory vesicles o Docking marker on vesicle → docking marker acceptor on plasma membrane (v-SNARE → t-SNARE) “lock and key” BALANCE OF ENDOCYTOSIS AND EXOCYTOSIS o Rate of processes are regulated to maintain a constant membrane surface area and cell volume (> 100% of plasma membrane can be used in an hour to wrap int ernalized vesicles) o Membrane is constantly restored, retrieved → recycled o Cells are differentially selective in what enters and leaves Downloaded by Sandra Salama ([email protected])