TOPIC-2-CELLULAR-LEVEL-OF-ORGANIZATION.pdf

JLAT,RMT ANATOMY AND PHYSIOLOGY LECTURE NOTES Prepared by: John Larry Amis Taberna,...

JLAT,RMT ANATOMY AND PHYSIOLOGY LECTURE NOTES Prepared by: John Larry Amis Taberna, RMT TOPIC 2: CELLULAR LEVEL OF ORGANIZATION CELLS ✓ average adult human body consists of more than 100 trillion cells ✓ basic, living, structural, and functional units of the body ✓ Each cell is a highly organized unit containing specialized structures called organelles (little organs) that perform specific function Functions of the Cell 1. Cell metabolism and energy use Energy released during metabolism is used for cell activities, such as the synthesis of new molecules, muscle contraction, and heat production, which helps maintain body temperature. 2. Synthesis of molecules Cells synthesize various types of molecules, including proteins, nucleic acids, and lipids. Structural and functional characteristics of cells are determined by the types of molecules they produce. 3. Communication Cells produce and receive chemical and electrical signals that allow them to communicate with one another. (ex. nerve cells communicate with muscle cells, causing muscle cells to contract. 4. Reproduction and inheritance Each cell contains a copy of the genetic information of the individual. Specialized cells (sperm cells and oocytes) PLASMA/CELL MEMBRANE ✓ flexible yet sturdy barrier that surrounds and contains the cytoplasm of a cell ✓ encloses the cytoplasm and forms the boundary between extracellular and intracellular substances ✓ acts as a selective barrier that determines what moves into and out of the cell ✓ plays a role in communication between cells Structure of Plasma membrane Lipid Bilayer basic structural framework of the plasma membrane made up of three types of lipid molecules: ▪ Phospholipid (75%) – lipids that contains phosphorous ▪ Cholesterol (20%) – a steroid with an attached hydroxyl (-OH) group ▪ Glycolipids (5%) – lipids with attached carbohydrate groups Lipids are Amphipathic (have both polar and non-polar parts) ▪ Polar – Hydrophilic head (contains phosphate) ▪ Non-polar – Two hydrophobic long fatty acid tails Phospholipid molecules orient themselves in the bilayer with their hydrophilic heads facing a watery fluid on either side— cytosol on the inside and extracellular fluid on the outside. The hydrophobic tails in each half of the bilayer point toward one another, forming a nonpolar, hydrophobic region in the membrane’s interior JLAT,RMT  JLAT,RMT Membrane Proteins Arrangement: Integral Proteins – extend into or through the lipid bilayer and are firmly embedded in it o Transmembrane protein – integral proteins that span the entire lipid bilayer and protrude into both the cytosol and extracellular fluid Peripheral Proteins – not firmly embedded in the membrane. They are attached to the polar heads of membrane lipids or to integral proteins at the inner or outer surface of the membrane. Functions: Function Arrangement Description Image reference pores or holes that specific ions, such as potassium ions (K+), can flow Ion Channel Integral Protein through to get into or out of the cell. Most ion channels are selective; they allow only a single type of ion to pass through. selectively moving a polar substance or ion from one Carriers/ Integral Protein side of the membrane to Transporters the other. serve as cellular recognition sites for specific type of molecule. Receptor Intergal Protein (ex. insulin receptors bind the hormone insulin) Ligand – specific molecule that binds to a receptor Enzyme Integral and Catalyze specific chemical Peripheral reactions at the inside or outside surface of the cell. JLAT,RMT  JLAT,RMT Anchors filaments inside Linker Integral and and outside the plasma Peripheral membrane, providing structural stability and shape for the cell. recognize other cells of the same kind during tissue Cell identity Glycoprotein formation or recognize and marker respond to potentially dangerous foreign cells. (ex. ABO blood group) Membrane Permeability Permeable – structure allows the passage of substances through it Impermeable – structure does not permit the passage of substances through it Selectively permeable – allows some substance to pass and restrict the others o Intracellular substances: enzymes, glycogen, and potassium ions (K+) o Extracellular substances: Na+, Ca2+ and Cl− Movement of substances through the cell: o Passive membrane transport – does not require the cell to expend energy o Active membrane transport – require the cell to expend energy, usually in the form of ATP Passive Membrane Transport Diffusion Solutes such as ions or molecules tend to move up or down the concentration gradient ▪ Leak channels – allows ions to pass through it constantly ▪ Gated channels – limits the movement of ions across membrane by opening and closing Types of diffusion: ▪ Simple diffusion – substances move freely through the lipid bilayer of cell membrane without the help of transport proteins Oxygen, CO2, Nitrogen gas, fatty acids, fat-soluble vitamins (A,D,E,K), small uncharged polar molecule such as water and urea Important for gas exchange (O2 and CO2) ▪ Facilitated diffusion – solutes that are too polar or highly charged move into the cell through integral proteins (channel or carrier) JLAT,RMT  JLAT,RMT Osmosis diffusion of water which are small enough to cross a selectively permeable membrane or through water channels. water diffuses toward areas of high solute concentration and dilutes those solutes. Two ways to pass through a membrane: ▪ Moving between neighboring phospholipid molecules in lipid bilayer ▪ Through aquaporins (water channels) Pressures involved in osmosis: ▪ Osmotic Pressure – proportional to the concentration of solute (ex. protein) that cannot pass through the membrane ▪ Hydrostatic Pressure – force of the fluid volume against a membrane. It depends upon the density(volume) of liquid and gravity. Osmotic pressure of cytosol is same with osmotic pressure of interstitial fluid outside cells which keeps the cell volume relatively constant. Tonicity of solution – measure of solution’s ability to change the cell volume by altering water content ▪ Isotonic solution – cell shape and volume is maintained (Ex. 0.9% NaCl or saline sol’n) ▪ Hypotonic solution – solution with lower concentration of solutes than the cytosol. Water molecules enter the cell faster than they leave become swollen then burst (lysis) ▪ Hypertonic solution – solution with higher concentration of solute than the cytosol (Ex. 2%NaCl sol’n). Water molecules move out of the cell faster than they enter causing shrinkage or Crenation Active Membrane Transport carrier-mediated process that moves substances across the cell membrane from regions of lower concentration to those of higher concentration against a concentration gradient requires energy in the form of ATP for carrier proteins to move solutes across the membrane against a concentration gradient. No ATP available, active transport stops. Solutes actively transported: o Na+, K+, H+, Ca2+, I− (iodide ions), and Cl− o Amino acids o Monosaccharides Primary Active Transport Energy source: Energy obtained from hydrolysis of adenosine triphosphate (ATP) Carrier protein is called pumps An energy changes the shape of the carrier protein which “pumps” a substance across a plasma membrane against its concentration gradient Sodium-Potassium Pump o expels sodium ions (Na+) from cells and brings potassium ions (K+) in o also called as sodium-potassium-ATPase because it can hydrolyze ATP to release energy o thousands of sodium-potassium pump can be seen in cells o work nonstop to maintain a low concentration of Na+ and a high concentration of K+ in the cytosol. o Importance: ▪ maintaining normal cell volume ▪ generate electrical signals such as action potentials ▪ maintain normal tonicity on each side of the plasma membrane JLAT,RMT  JLAT,RMT Secondary Active Transport Energy source: Stored energy in Na+ during the primary active transport is used to energize the carrier. It doesn’t use ATP directly but rather uses the energy stored in sodium to energize a pump thus the term “secondary” The diffusion of transported substance down its concentration gradient (Na+) provides the energy to transport a second substance (ex. glucose) Symporters/Cotransport – transporters move two substances in the same direction Antiporters/Countertransport – diffusing substance moves in a direction opposite to that of the transported substance JLAT,RMT  JLAT,RMT CYSTIC FIBROSIS Genetic disorder resulting from an abnormality in Cl− channels Three types: o Defective channel protein failed to reach the cell membrane from the site of its synthesis o Channel fails to bind ATP o Channel reached the membrane and binds ATP but do not open Normally, chloride moves out the cell and followed by water to prevent mucus thickening on the tubes lined by cells. Pathophysiology: o Defective channel transport causes thickening of mucus leading to obstruction of tubes/ducts o Associated disease: ▪ Chronic pneumonia ▪ buildup of thick mucus in the pancreatic and hepatic ducts blocks them so that pancreatic digestive enzymes and bile salts cannot reach the small intestine ▪ fats and fat-soluble vitamins (require bile salts for absorption and digestion) without pancreatic enzymes, are not taken up by intestinal cells in normal amounts. The patient suffers from deficiencies of vitamins A, D, E, and K night blindness skin disorders rickets excessive bleeding VESICLE TRANSPORTS Vesicle Vesicule – little blister or bladder. A small spherical sac. Transports large water-soluble molecules, small pieces of matter, and even whole cells across cell membranes The fluid nature of membranes, vesicles and cell membranes can fuse, allowing the contents of the vesicles to cross the cell membrane Endocytosis is the uptake of material through the cell membrane by the formation of a vesicle the cell membrane invaginates (folds inward) to form a vesicle containing the material to be taken into the cell The vesicle then moves into the cytoplasm Receptor Mediated Endocytosis ✓ It exhibits specificity because the cell membrane contains specific receptor molecules that bind to specific substances. ✓ When a specific substance binds to the receptor molecule, endocytosis is triggered and the substance is transported into the cell ✓ Molecules taken up by the process: Cholesterol and growth factors JLAT,RMT  JLAT,RMT Process of Receptor Mediated Endocytosis 1. Binding a. On the extracellular side of the plasma membrane an LDL particle binds to a specific receptor in the plasma membrane to form a receptor–LDL complex. b. The protein receptors called clathrin-coated pits (clathrin) attaches to the membrane on its cytoplasmic side. c. Many clathrin molecules come together, forming a basketlike structure around the receptor–LDL complexes that causes the membrane to invaginate (fold inward) 2. Vesicle formation a. The invaginated edges of the membrane around the clathrin-coated pit fuse, and a small piece of the membrane pinches off producing the clathrin-coated vesicle that contains the receptor–LDL complex 3. Uncoating a. Clathrin-coated vesicle loses its clathrin coat to become an uncoated vesicle. b. Clathrin molecules either return to the inner surface of the plasma membrane or help form coats on other vesicles inside the cell. JLAT,RMT  JLAT,RMT 4. Fusion with endosome a. The uncoated vesicle quickly fuses with an endosome. b. Within an endosome, the LDL particles separate from their receptors. 5. Recycling of receptors to plasma membrane a. Most of the receptors accumulate in elongated protrusions of the endosome b. Protrusion pinch off , forming transport vesicles that return the receptors to the plasma membrane. c. An LDL receptor is returned to the plasma membrane about 10 minutes aft er it enters a cell 6. Degradation in lysosomes a. Other transport vesicles, which contain the LDL particles, bud off the endosome and soon fuse with a lysosome. b. Lysosomes contain many digestive enzymes that break down the large protein and lipid molecules of the LDL particle into amino acids, fatty acids, and cholesterol. ▪ Cholesterol – rebuilding membranes and for synthesis of steroids, such as estrogen. ▪ Fatty acids and amino acids – for ATP production or to build other molecules needed by the cell Phagocytosis “cell eating” is a form of endocytosis in which the cell engulfs large solid particles, such as worn-out cells, whole bacteria, or viruses Two main phagocytes: o Macrophage – located in body tissues o Neutrophil – type of WBC located in the blood Pinocytosis/Bulk-phase endocytosis “cell-drinking” much smaller vesicles are formed, and they contain liquid rather than particles No receptor proteins are involved; all solutes dissolved in the extracellular fluid are brought into the cell. occurs in most cells, especially absorptive cells in the intestines and kidneys Exocytosis releases materials from a cell ex. secretion of digestive enzymes by the pancreas. secretion of mucus by the salivary glands. JLAT,RMT  JLAT,RMT CYTOPLASM consist of all the cellular contents between plasma membrane and the nucleus two components: o Cytosol o Organelles Cytosol ✓ Fluid portion the cytoplasm that surround the organelles ✓ It constitutes about 55% of total cell volume ✓ Consists of 75-90% water and dissolved and suspended components (Ions, Glucose, Amino acids, Fatty acids, Proteins, Lipids, ATP and waste products) ✓ Site of chemical reactions (glycolysis) ✓ Cytoskeleton o Network of protein filaments that extends throughout the cytosol o Contributes to the structure of the cell ▪ Microfilament ✓ Thinnest element of cytoskeleton ✓ Composed of proteins (actin and myosin) ✓ Functions: o Generate movement – muscle contraction, cell division, cell locomotion (WBC migration) o Provide mechanical support – for basic strength and shape of cells. It anchors the cytoskeleton to integral proteins in plasma membrane o Supports the microvilli in the cell surface Microvilli “micro”- small; “villi” - tufts of hair Non-motile, microscopic fingerlike projection of plasma membrane Increases the surface area of a cell for absorption (EC in the small intestine) ▪ Intermediate Filament ✓ Thicker than microfilaments but thinner than microtubules ✓ Found on parts of cell subject to mechanical stress ✓ Help stabilize the position of organelles such as the nucleus and help attach cells to one another ▪ Microtubules ✓ Largest of the cytoskeleton components ✓ Long, unbranched hollow tubes ✓ Composed mainly of protein (tubulin) ✓ Its assembly begins in the centrosome and grow toward the cell periphery ✓ Supports the cytoplasm of cells, assisting in cell division, and forming essential components of certain organelles, such as cilia and flagella. JLAT,RMT  JLAT,RMT Cilia Hair-like structure that project from the surface of cells composed of microtubules, organized in a pattern similar to that of centrioles, which are enclosed by the plasma membrane Numerous on surface of cells that lines the respiratory tract Sweeps foreign particles trapped in mucus away from lungs Its action is compromised in case of Cystic Fibrosis Pathophysiology: o Cilia is paralyzed by nicotine. Thus, smokers cough often to remove foreign particles from their airways o Fallopian tube is lined by cilia. In smokers, increased risk of ectopic pregnancy Flagella Similar structure with cilia but much longer Moves the entire cell Sperm cell – only flagellated cell in human body JLAT,RMT  JLAT,RMT ORGANELLES Specialized structure within the cells that has characteristic shapes, perform specific functions in cellular growth, maintenance and reproduction Interference among many chemical reactions in each cell is prevented because each reactions are confined to different organelles Each organelles has an enzyme for biochemical processes Centrosome Microtubule organizing center Located near the nucleus Two components: ▪ Pair of centrioles small, cylindrical organelle composed of nine triplets; each triplet consists of three parallel microtubules joined together ▪ Pericentriolar matrix Surrounds the centriole Contains hundreds of ring-shaped complexes composed of protein tubulin Tubulins are the organizing centers for formation of mitotic spindle (cell division) and microtubule formation (non-dividing cells) Centrosome replicates during cell division so that succeeding generations of cells have the capacity for cell division Ribosomes Organelles where proteins are produced Composed of large and small subunits which are made separately in the nucleolus Location: ▪ Attached in the Endoplasmic Reticulum synthesize proteins destined for: o specific organelles o for insertion in the plasma membrane o for export from the cell ▪ Free Ribosomes Free in the cytoplasm Synthesize proteins used in the cytosol JLAT,RMT  JLAT,RMT Rough Endoplasmic Reticulum network of membranes in the form of flattened sacs or tubules Two types: ▪ Rough Endoplasmic Reticulum Outer surface is studded with ribosomes (protein synthesis) extends from the outer nuclear membrane into the cytoplasm Synthesized protein enter spaces within the ER for processing and sorting o May be attached to carbohydrates to form Glycoprotein or to phospholipids (also synthesized by ER) o glycoproteins and phospholipids may be incorporated into the membranes of organelles, inserted into the plasma membrane, or secreted via exocytosis ▪ Smooth Endoplasmic Reticulum does not have ribosomes on the outer surfaces of its membrane extends from the rough ER functions: o synthesizes fatty acids and steroids (estrogens and testosterone) o it liver cells, it inactivates or detoxifies drugs and other potentially harmful substances o removes the phosphate group from glucose-6-phosphate to allow free glucose enter the circulation o sarcoplasmic reticulum stores and releases calcium ions that trigger contraction in muscle cells Smooth ER and Drug Tolerance With repeated exposure to drugs, the amount of smooth ER and its enzymes increases to protect the cell from its toxic effects. As the amount of smooth ER increases, higher and higher dosages of the drug are needed to achieve the original effect. This could result in an increased possibility of overdose and increased drug dependence. Golgi Complex o consists of 3 to 20 cisterns(cavities), small, flattened membranous sacs with bulging edges that resemble a stack of pita bread o collects, modifies, packages, and distributes proteins and lipids manufactured by the ER o Different enzymes in the entry, medial, and exit cisterns permit each of these areas to modify, sort, and package o Entry (cis) face ▪ cistern that faces the rough ER ▪ receives and modifies proteins produced by the rough ER o Exit (trans) face ▪ cistern that faces the plasma membrane ▪ add carbohydrates to proteins to form glycoproteins and lipids to proteins to form lipoproteins o Medial cisterns – Sacs between the entry and exit faces ▪ modifies the molecules further and then sorts and packages them for transport to their destinations JLAT,RMT  JLAT,RMT 1. Proteins synthesized by ribosomes on the rough ER are surrounded by a piece of the ER membrane, which eventually buds from the membrane surface to form transport vesicles. 2. Transport vesicles move toward the entry face of the Golgi complex. 3. Fusion of several transport vesicles creates the entry face of the Golgi complex and releases proteins into its lumen (space). 4. The proteins move from the entry face into one or more medial cisterns. a. Enzymes in the medial cisterns modify the proteins to form glycoproteins, glycolipids, and lipoproteins. b. Transfer vesicles that bud from the edges of the cisterns move specific enzymes back toward the entry face and move some partially modified proteins toward the exit face 5. The products of the medial cisterns move into the lumen of the exit face. 6. Within the exit face cistern, the products are further modified and are sorted and packaged. 7. Some of the processed proteins leave the exit face and are stored in secretory vesicles. a. These vesicles deliver the proteins to the plasma membrane and discharged by exocytosis into the extracellular fluid. (ex. certain pancreatic cells release the hormone insulin in this way) 8. Other processed proteins leave the exit face in membrane vesicles that deliver their contents to the plasma membrane for incorporation into the membrane. 9. Finally, some processed proteins leave the exit face in transport vesicles that will carry the proteins to another cellular destination. a. transport vesicles carry digestive enzymes to lysosomes SECRETORY VESICLES a small, membrane-bound sac that pinch off from the Golgi apparatus to transport or store materials within cells. In many cells, they accumulate in the cytoplasm and are released to the exterior when the cell receives a signal o Ex. insulin remains in the cytoplasm of pancreatic cells until rising blood glucose levels stimulate its secretion JLAT,RMT  JLAT,RMT Lysosomes o membrane-bound vesicles formed from the Golgi apparatus o contain a variety of enzymes that function as intracellular digestive systems o functions: ▪ Digest substances that enter a cell via endocytosis and transport final products of digestion into cytosol. ▪ Carry out autophagy, the digestion of worn-out organelles. organelle to be digested is enclosed by a membrane derived from the ER to create a vesicle called an autophagosome then fuses with a lysosome. ▪ Implement autolysis, the digestion of an entire cell (pathologic or post-mortem) o Pathophysiology: ▪ Pompe Disease – inability of lysosomal enzymes to break down the carbohydrate glycogen. the accumulation of glycogen in heart muscle cells often leads to heart failure ▪ Lipid-storage disorders – accumulation of large amounts of lipids in cells that lack the enzymes necessary to break down the lipids Tay Sach’s Disease - Buildup of lipids in the brain that leads to neurological problems, such as blindness, deafness, and paralysis. No successful treatment yet. Peroxisomes o small, membrane-bound vesicles containing enzymes that break down fatty acids, amino acids, and hydrogen peroxide (H2O2) o very abundant in the liver, where detoxification of alcohol and other damaging substances occurs ▪ hydrogen peroxide (H2O2) is a by-product of fatty acid and amino acid breakdown and can be toxic to a cell. Thus, broken down to water and O2 through the enzyme catalase Proteasomes o destroys unneeded, damaged, or faulty proteins o unneeded protein includes those involved in negative feedback mechanism. Once used and the response has been achieved, it is destroyed. Mitochondria o referred to as the “powerhouses” of the cell o generate most of the ATP through aerobic respiration o their number depends on the function of cells o Parts: ▪ External Mitochondrion Membrane ▪ Internal Mitochondrion Membrane ▪ Mitochondrial Cristae – folds within the IMM ▪ Mitochondrial Matrix - fluid-filled cavity of mitochondrion o Function: ▪ Release of Cytochrome C in the cytosol when cell is in distress Within the mitochondria – involved in ATP production In the cytosol – triggers apoptosis ▪ Basis for maternal relationship identity mitochondrial genes are inherited only from mothers because all mitochondria in a cell are descendants of those that were present in the oocyte (egg) during the fertilization process head of a sperm normally lacks organelles such as mitochondria JLAT,RMT  JLAT,RMT Nucleus o large organelle usually located near the center of the cell o matured RBC – nonnucleated cell o skeletal muscle cells and a few other types of cells – multiple nuclei. o Nuclear envelope – consists of outer and inner membranes that separates nucleus from cytoplasm o Nuclear pore – an area through which materials can pass into or out of the nucleus ▪ Small molecules and ions – passive diffusion ▪ Most large molecules, such as RNAs and proteins – active transport process o Genes – arranged along chromosomes. Cell’s hereditary units which control cellular structure and direct cellular activities o Genome – total genetic information carried in a cell or an organism o Chromosomes ▪ consist of DNA and Proteins ▪ 46 chromosomes, 23 inherited from each parent (22 autosome; 1sex chromosome) o Chromatin – chromosomes that are loosely coiled and become tightly coiled during cell division o Chromatin fiber – coil of nucleosomes into a larger-diameter promoted by another histone o Chromatids – formed before cell division; DNA replicates and loop become more condensed. o Nucleoli ▪ a cluster of protein, DNA, and RNA; it is not enclosed by a membrane ▪ Usually, one to several nucleoli within the nucleus ▪ It forms the subunits of ribosome Formation of Ribosomal Subunits: JLAT,RMT