Cell Physiology PDF

CELL PHYSIOLOGY Prof. Dr. Senol DANE LEARNING OBJECTIVES At the end of this lecture, you will be able to:  Define a cell  List the three major regions of a generalised ce...

CELL PHYSIOLOGY Prof. Dr. Senol DANE LEARNING OBJECTIVES At the end of this lecture, you will be able to:  Define a cell  List the three major regions of a generalised cell and their functions CELLS  Just as bricks are the structural units of a house, cells are the structural units of all living things, from one-celled like amoebas to multicellular organisms such as humans  The human body has approximately 100 trillion of cells THE CELL  The English scientist Robert Hooke first observed plant cells with a crude microscope in the late 1600s  Then, in the 1830s two German scientists, Matthias Schleiden and Theodor Schwann, proposed that all living things are composed of cells  German pathologist Rudolf Virchow extended this idea by contending that cells arise only from other cells. CELL  A cell is the basic structural and functional unit of living organisms  When you define cell properties, you define the properties of life  The activity of an organism depends on both the individual and collective activities of its’ cells  Continuity of life from one generation to another has a cellular basis CELL  The cell is the microscopic package that contains all the parts necessary to survive.  Therefore, loss of cellular homeostasis underlies virtually every disease.  Homeostasis means ‘health’. CELLS  The trillions of cells in the human body include over 200 different cell types that vary in shape, size, and function.  The disc-shaped red blood cells, branching nerve cells, and cube-like cells of kidney tubules are just a few examples.  Cells also vary in length-ranging from 2 µm in the smallest cells to over a meter in the nerve cells.  A cell’s shape reflects its function. CELLS  Regardless of type, all cells are composed chiefly of carbon, hydrogen, nitrogen, oxygen, and trace amounts of several other elements.  In addition, all cells have the same basic parts and some common functions. CELLS  A human cell has three main parts: 1. The plasma membrane: the outer boundary of the cell. 2. The cytoplasm: the intracellular fluid packed with organelles, small structures that perform specific cell functions. 3. The nucleus: an organelle that controls cellular activities. Typically, the nucleus lies near the cell’s center. THE PLASMA MEMBRANE LEARNING OBJECTIVES  Describe the chemical composition of the plasma membrane and relate it to membrane functions. PLASMA MEMBRANE  The flexible plasma membrane defines the extent of a cell, separating two of the body’s major fluid compartments-the intracellular fluid and the extracellular fluid.  The term cell membrane is commonly used as a synonym for plasma membrane.  All organelles are enclosed in the same membrane.  The plasma membrane is not a passive envelope.  Its unique structure allows it to play a dynamic role in cellular activities. THE FLUID MOSAIC MODEL  The fluid mosaic model of membrane structure depicts the plasma membrane as an exceedingly thin (7–10 nm) structure composed of a double layer, or bilayer, of lipid molecules with protein molecules “plugged into” or dispersed in it.  The proteins, many of which float in the fluid lipid bilayer, form a constantly changing mosaic pattern. The model is named for this characteristic, the fluid mosaic model. MEMBRANE LIPIDS  The lipid bilayer forms the basic “fabric” of the membrane.  It is constructed largely of :  phospholipids,  with smaller amounts of glycolipids,  cholesterol, and  areas called lipid rafts. PHOSPHOLIPIDS  Each lollipop-shaped phospholipid molecule has a polar “head” that is charged and is hydrophilic, and an uncharged, nonpolar “tail” that is made of two fatty acid chains and is hydrophobic.  The polar heads are attracted to water and so they lie on both the inner and outer surfaces of the membrane.  The nonpolar tails, being hydrophobic, avoid water and line up in the center of the membrane.  All plasma membranes share a sandwich-like structure  They are composed of two parallel sheets of phospholipid molecules lying tail to tail, with their polar heads exposed to water on either side of the membrane or organelle. GLYCOLIPIDS  Lipids with attached sugar groups.  Found only on the outer plasma membrane surface, account for about 5% of total membrane lipids.  Their sugar groups, like the phosphate- containing groups of phospholipids, make that end of the glycolipid molecule polar, whereas the fatty acid tails are nonpolar. CHOLESTEROL  Some 20% of membrane lipid is cholesterol.  Like phospholipids, cholesterol has a polar region (its hydroxyl group) and a nonpolar region (its fused ring system).  It wedges its platelike hydrocarbon rings between the phospholipid tails, stabilizing the membrane, while decreasing the mobility of the phospholipids and the fluidity of the membrane. MEMBRANE PROTEINS  Plasma membrane proteins allow the cell to communicate with its environment.  Proteins make up about half of the plasma membrane by mass and are responsible for most of the specialized membrane functions.  Some membrane proteins float freely. Others are “tethered” to intracellular structures that make up the cytoskeleton and are restricted in their movement.  There are two distinct populations of membrane proteins, integral and peripheral. INTEGRAL PROTEINS  Integral proteins are firmly inserted into the lipid bilayer.  Some protrude from one membrane face only, but most are trans-membrane proteins that span the entire membrane and protrude on both sides.  All integral proteins have both hydrophobic and hydrophilic regions.  This feature allows them to interact with both the nonpolar lipid tails and the water inside and outside the cell. INTEGRAL PROTEINS  Transmembrane (integral) proteins may be:  Channels through which small, water-soluble molecules or ions can move, thus bypassing the lipid part of the membrane.  Carriers that bind to a substance and then move it through the membrane.  Enzymes  Receptors for hormones or other chemical messengers and relay messages to the cell interior—a process called signal transduction. PERIPHERAL PROTEINS  Peripheral proteins are not embedded in the lipid bilayer.  They attach loosely to integral proteins and are easily removed without disrupting the membrane.  Peripheral proteins include a network of filaments that helps support the membrane from its cytoplasmic side.  Peripheral proteins may  Act as enzymes  Act as motor proteins involved in mechanical functions, such as changing cell shape during cell division and muscle cell contraction.  link cells together LIPID RAFTS  About 20% of the outer membrane surface contains lipid rafts.  They are dynamic assemblies of saturated phospholipids associated with unique lipids called sphingolipids and lots of cholesterol.  Lipid rafts are more stable and less fluid than the rest of the membrane, and they can include or exclude specific proteins.  Lipid rafts are concentrating platforms for certain receptor molecules or for protein molecules needed for cell signaling, membrane invagination, or other functions. LIPID RAFTS THE GLYCOCALYX  Glycocalyx is the fuzzy, sticky, carbohydrate-rich area at the cell surface. Our cells are sugar- coated.  Is enriched both by glycolipids and by glycoproteins secreted by the cell.  Because every cell type has a different pattern of sugars in its glycocalyx, the glycocalyx provides highly specific biological markers by which approaching cells recognise each other.  For example, a sperm recognises an ovum by the ovum’s unique glycocalyx. Cells of the immune system identify a bacterium by binding to certain membrane glycoproteins in the bacterial glycocalyx. APPLIED PHYSIOLOGY  Definite changes occur in the glycocalyx of a cell that is becoming cancerous.  A cancer cell’s glycocalyx may change almost continuously, allowing it to keep ahead of immune system recognition mechanisms and avoid destruction. CYTOPLASM LEARNING OBJECTIVES By the end of this lecture, you will be able to:  Describe the composition of the cytosol.  Discuss the structure and function of mitochondria.  Discuss the structure and function of ribosomes, the endoplasmic reticulum, and the Golgi apparatus, including functional interrelationships among these organelles.  Compare the functions of lysosomes and peroxisomes. CYTOPLASM  Is the cellular material between the plasma membrane and the nucleus  Is the site of most cellular activities  The electron microscope reveals that it consists of three major elements:  the cytosol,  inclusions, and  organelles. CYTOSOL  The cytosol is the viscous, semitransparent fluid in which the cytoplasmic elements are suspended.  It is a complex mixture with properties of both a colloid and a true solution.  Dissolved in the cytosol, which is largely water, are proteins, salts, sugars, and a variety of other solutes.  The organelles are the metabolic machinery of the cell.  Each type of organelle carries out a specific function. INCLUSIONS  Inclusions are chemical substances that may or may not be present, depending on cell type.  Examples include stored nutrients, such as the glycogen granules in liver and muscle cells; lipid droplets in fat cells; pigment (melanin) granules in certain skin and hair cells; and crystals of various cell types. CYTOPLASMIC ORGANELLES  The organelles are specialized cellular compartments or structures, each performing its own job to maintain the life of the cell.  Some organelles, the nonmembranous organelles, lack membranes (cytoskeleton, centrioles, and ribosomes).  Most organelles are bounded by a membrane like the plasma membrane. This membrane enables the membranous organelles (peroxisomes, lysosomes, endoplasmic reticulum, and Golgi apparatus) to maintain an internal environment different from that of the surrounding cytosol.  This compartmentalization is crucial to cell functioning. Without it, thousands of enzymes would be mixed, and biochemical activity would be chaotic. MITOCHONDRIA  Mitochondria are membranous organelles. They elongate and change shape continuously.  They are the power plants of a cell, providing most of its ATP supply.  The density of mitochondria in a particular cell reflects its energy requirements, and mitochondria generally cluster where the action is.  Busy cells like kidney and liver cells have hundreds of mitochondria, whereas relatively inactive cells have just a few. MITOCHONDRIA  A mitochondrion is enclosed by two membranes.  The outer membrane is smooth, but the inner membrane folds inward, forming shelf-like cristae that protrude into the matrix.  Food fuels (glucose and others) are broken down to water and CO2 by enzymes, some dissolved in the mitochondrial matrix and others forming part of the crista membrane.  As the metabolites are broken down and oxidized, some of the energy released is captured and used to attach phosphate groups to ADP molecules to form ATP.  This mitochondrial process is called aerobic cellular respiration (oxidative phosphorylation) because it requires oxygen. MITOCHONDRIA  Mitochondria contain their own DNA, RNA, and ribosomes and can reproduce themselves.  Mitochondrial genes direct the synthesis of 1% of the proteins required for mitochondrial function, and the DNA of the cell’s nucleus encodes the remaining proteins needed to carry out cellular respiration.  If cellular requirements for ATP increase, the mitochondria synthesise more cristae or simply pinch in half (a process called fission) to increase their number, then grow to their former size. RIBOSOMES  Ribosomes are small, dark-staining granules composed of proteins and a variety of RNAs called ribosomal RNAs.  Ribosomes are sites of protein synthesis.  Some ribosomes float freely in the cytoplasm.  Others are attached to membranes, forming a complex called the rough (granular) endoplasmic reticulum. RIBOSOMES  Free ribosomes float freely in the cytoplasm. They make soluble proteins in the cytosol, as well as those imported into mitochondria and some other organelles.  Membrane-bound ribosomes are attached to membranes, forming a complex called the rough endoplasmic reticulum.  They synthesize proteins destined either for incorporation into cell membranes or lysosomes, or for export from the cell. ENDOPLASMIC RETICULUM (ER)  ER is an extensive system of interconnected tubes and parallel membranes enclosing fluid filled cavities, or cisterns.  The ER is continuous with the outer nuclear membrane and accounts for about half of the cell’s membranes.  There are two distinct varieties:  Granular (rough) ER  Agranular (smooth) ER. ENDOPLASMIC RETICULUM ROUGH ENDOPLASMIC RETICULUM  The external surface of the rough ER is studded with ribosomes.  Proteins assembled on these ribosomes thread their way into the fluid-filled interior of the ER cisterns.  When complete, the newly made proteins are enclosed in vesicles for their journey to the Golgi apparatus where they undergo further processing. THE ROUGH ER HAS SEVERAL FUNCTIONS:  Its ribosomes manufacture all proteins secreted from cells. For this reason, the rough ER is particularly abundant and well developed in most secretory cells, antibody-producing plasma cells, and liver cells, which produce most blood proteins.  It is also the cell’s “membrane factory” where integral proteins and phospholipids that form part of all cellular membranes are manufactured.  The enzymes needed to catalyse lipid synthesis have their active sites on the external (cytosolic) face of the ER membrane, where the needed substrates are readily available. SMOOTH ENDOPLASMIC RETICULUM  The smooth ER is continuous with the rough ER and consists of tubules arranged in a looping network.  Its enzymes play no role in protein synthesis.  Instead, the enzymes catalyse reactions involved with the following tasks: 1. Metabolise lipids, synthesise cholesterol, and synthesise the lipid components of lipoproteins (in liver cells) SMOOTH ENDOPLASMIC RETICULUM 2. Synthesise steroid-based hormones such as sex hormones (testosterone-synthesising cells of the testes are full of smooth ER) 3. Absorb, synthesise, and transport fats (in intestinal cells) 4. Detoxify drugs, certain pesticides, and cancer-causing chemicals (in liver and kidneys) 5. Break down stored glycogen to form free glucose (in liver cells especially) SARCOPLASMIC RETICULUM  Skeletal and cardiac muscle cells have an elaborate smooth ER (sarcoplasmic reticulum) that plays an important role in storing and releasing calcium ions during muscle contraction.  Except for the prior examples, most body cells contain relatively little smooth ER. GOLGI APPARATUS  The Golgi apparatus consists of stacked and flattened membranous sacs, shaped like hollow dinner plates.  The Golgi apparatus is the principal “traffic director” for cellular proteins.  Its major function is to modify, concentrate, and package the proteins and lipids made at the rough or smooth ER and destined for export from the cell.  Transport vesicles that bud off from the rough ER move to and fuse with the membranes of the Golgi apparatus.  Inside the apparatus, the proteins are modified.  Some sugar groups are trimmed while others are added, and in some cases, phosphate groups are added. GOLGI APPARATUS GOLGI APPARATUS  The various proteins are “tagged” for delivery to a specific address, sorted, and packaged in vesicles:  Vesicles containing proteins destined for export pinch off from the trans face as secretory vesicles, which migrate to the plasma membrane and discharge their contents from the cell by exocytosis.  Specialised secretory cells, such as the enzyme-producing cells of the pancreas, have a lot of Golgi apparatus.  The Golgi apparatus pinches off other vesicles containing lipids and transmembrane proteins destined for the plasma membrane or for other membranous organelles.  The Golgi apparatus also packages digestive enzymes into lysosomes. GOLGI APPARATUS PEROXISOMES  Peroxisomes are spherical membranous sacs containing a variety of powerful enzymes, the most important of which are oxidases and catalases.  It neutralizes free radicals, highly reactive chemicals with unpaired electrons that can damage the biological molecules  Oxidases use molecular oxygen (O2) to detoxify harmful substances, including alcohol and formaldehyde.  Oxidases convert free radicals to hydrogen peroxide, which is also reactive and dangerous but which the catalases quickly convert to water.  Free radicals and hydrogen peroxide are normal by- products of cellular metabolism  They have devastating effects on cells if allowed to accumulate. PEROXISOMES  Peroxisomes are numerous in liver and kidney cells, which are very active in detoxification.  They also play a role in energy metabolism by breaking down and synthesizing fatty acids.  Peroxisomes look like small lysosomes  Peroxisomes form by budding off the smooth endoplasmic reticulum. LYSOSOMES  They are spherical membranous organelles containing activated digestive enzymes.  Lysosomes are large and abundant in phagocytes, the cells that dispose of invading bacteria and cell debris.  Lysosomal enzymes can digest almost all kinds of biological molecules.  They work best in acidic conditions and so are called acid hydrolases. LYSOSOMES  The lysosomal membrane is adapted to serve lysosomal functions in two important ways. 1. It contains H+ (proton) “pumps,” which are ATPases that gather hydrogen ions from the surrounding cytosol to maintain the organelle’s acidic pH. 2. It retains the dangerous acid hydrolases while permitting the final products of digestion to escape so that they can be used by the cell or excreted. In this way, lysosomes provide sites where digestion can proceed safely within a cell. LYSOSOMES  Lysosome functions:  Digest particles taken in by endocytosis, particularly ingested bacteria, viruses, and toxins  Degrade worn-out or nonfunctional organelles  Perform metabolic functions, such as glycogen breakdown and release  Break down non-useful tissues, such as the webs between the fingers and toes of a developing fetus and the uterine lining during menstruation  Breaking down bone to release calcium ions into the blood  The lysosomal membrane is ordinarily quite stable, but it becomes fragile when the cell is injured or deprived of oxygen and when excessive amounts of vitamin A are present.  When lysosomes rupture, the cell digests itself, a process called autolysis.  Autolysis is the basis for desirable destruction of cells. REGRESSION OF TISSUE  Tissues often regress to a smaller size.  This occurs in the uterus after pregnancy; in muscles during long inactivity and in mammary glands after lactation.  Lysosomes are responsible for this regression.  Lack of activity increases lysosomal activity  Lysosomes contain bactericidal agents that can kill bacteria: lysozyme, lysoferrin, acid at a pH 5.0 APPLIED PHYSIOLOGY  Lysosomes degrade glycogen and certain lipids in the brain at a relatively constant rate. In Tay- Sachs disease, an inherited condition seen mostly in Jews from Central Europe, the lysosomes lack an enzyme needed to break down a glycolipid abundant in nerve cell membranes. As a result, the nerve cell lysosomes swell with undigested lipids, which interfere with nervous system functioning. Affected infants typically have doll- like features and pink translucent skin. At 3 to 6 months of age, the first signs of disease appear (motor weakness). These symptoms progress to mental retardation, seizures, blindness, and ultimately death within 18 months. THE ENDOMEMBRANE SYSTEM  The endomembrane system is a system of organelles that work together mainly to: 1. produce, degrade, store, and export biological molecules, and 2. degrade potentially harmful substances.  It includes the ER, Golgi apparatus, transport and secretory vesicles, and lysosomes, as well as the nuclear membrane.  There are continuities between the nuclear envelope and the rough and smooth ER.  The plasma membrane, which is not an endomembrane, is also functionally part of this system.  Some of the vesicles “born” in the ER migrate to and fuse with the Golgi apparatus or the plasma membrane, and vesicles arising from the Golgi apparatus can become part of the plasma membrane, secretory vesicles, or lysosomes. The Endomembr ane System CYTOSKELETON LEARNING OBJECTIVES By the end of this lecture, you should be able to:  Name and describe the structure and function of cytoskeletal elements. CYTOSKELETON  The cytoskeleton is a network of rods running through the cytosol and accessory proteins that link these rods to other cell structures.  It acts as a cell’s “bones,” “muscles,” and “ligaments” by supporting cellular structures and providing the machinery to generate various cell movements.  The 3 types of rods in the cytoskeleton:  microfilaments,  intermediate filaments, and  microtubules.  None of these are membrane covered. CYTOSKELETON  MICROFILAMENTS  The thinnest elements of the cytoskeleton are semiflexible actin strands  Each cell has its own unique arrangement of microfilaments.  All cells have a dense cross-linked network of microfilaments, called the terminal web, attached to the cytoplasmic side of their plasma membrane.  The web strengthens the cell surface, resists compression, and transmits force during cellular movements and shape changes. MICROFILAMENTS  Most microfilaments are involved in cell motility or changes in cell shape.  For example, actin filaments interact with another protein, myosin, to generate contractile forces in a cell.  This interaction also forms the cleavage furrow that pinches one cell into two during cell division.  Microfilaments attached to cell adhesion molecules are responsible for amoeboid motion, and for the membrane changes like endocytosis and exocytosis.  Except in muscle cells, actin filaments are constantly breaking down and re-forming from smaller subunits.  Cell Division Amoeboid Motion with Endo- and Exocytosis  INTERMEDIATE FILAMENTS  Intermediate filaments are tough, insoluble protein fibers.  They are the most stable and permanent.  They attach to desmosomes, and their job is to act as wires to resist the forces exerted on the cell.  Because their protein composition varies in different cells, they have numerous names-for example, they are called neurofilaments in nerve cells and keratin MICROTUBULES  The elements with the largest diameter, hollow tubes made of spherical protein subunits called tubulins.  They radiate from a small region of cytoplasm near the nucleus called the centrosome.  They are dynamic organelles, constantly growing out from the centrosome, disassembling, and then reassembling.  The stiff but bendable microtubules determine the shape of the cell, as well as the distribution of cellular organelles. MICROTUBULES  Mitochondria, lysosomes, and secretory vesicles attach to the microtubules.  Tiny protein machines called motor proteins (kinesins, dyneins, and others) continually move and reposition the organelles along the microtubules.  Motor proteins work by changing their shapes. Powered by ATP, some motor proteins appear to act like train engines moving substances along on the microtubular “railroad tracks.”  Others move “hand over hand” somewhat like an orangutan-gripping, releasing, and then gripping again at a new site further along the microtubule MOVEMENT AND REPOSITION OF THE ORGANELLES ALONG THE MICROTUBULES  https://www.youtube.com/watch? v=9RUHJhskW00 CENTROSOMES, CENTRIOLES AND CELLULAR EXTENSIONS CENTROSOME  Microtubules are anchored at one end to the centrosome.  The centrosome acts as a microtubule organizing center.  It has a matrix that contains paired centrioles, small, barrel-shaped organelles oriented at right angles to each other.  The centrosome matrix generates microtubules and organizes the mitotic spindle in cell division. CENTRIOLES  Each centriole consists of a pinwheel array of nine triplets of microtubules, each connected to the next by nontubulin proteins and arranged to form a hollow tube.  Centrioles are known as basal bodies form the bases of cilia and flagella.  The “9 + 2” pattern of microtubules in the cilium or flagellum itself (nine doublets, or pairs, of microtubules encircling one central pair) differs from that of a centriole (nine microtubule triplets). CILIA  Cilia are motile extensions on the surfaces of certain cells.  Ciliary action moves substances in one direction.  For example, ciliated cells that line the respiratory tract propel mucus laden with dust particles and bacteria upwards, away from the lungs.  When a cell is about to form cilia, the centrioles multiply and line up beneath the plasma membrane at the cell’s surface.  Microtubules then “sprout” from each centriole, forming the ciliary projections. CILIATED CELLS THAT LINE THE RESPIRATORY TRACT CILIA  The cilium has flexible cross-linking proteins, and motor proteins (dynein arms) that promote its movement.  The dynein arms of one microtubule doublet grips its adjacent doublet, and powered by ATP, pushes it up, releases, and then re-grips.  Because the doublets are physically restricted by other proteins, they cannot slide far and are forced to bend.  The collective bending of all the doublets causes the cilium to bend.  As a cilium moves, it alternates rhythmically between a propulsive power stroke, when it is nearly straight and moves in an arc, and a recovery stroke, when it bends and returns to its initial position.  The cilium produces a pushing motion in a single direction that repeats some 10 to 20 times per second.  The bending of one cilium is quickly followed by the bending of the next and then the next, creating a current at the cell FLAGELLA  Flagellum is projections formed by centrioles but is longer than cilia.  The only flagellated cell in the human body is sperm, which has one propulsive flagellum, commonly called a tail.  Cilia propel other substances across a cell’s surface, whereas a flagellum propels the cell itself. FLAGELLA OF THE SPERM CELL MICROVILLI  Microvilli are minute, fingerlike extensions of the plasma membrane that project from an exposed cell surface.  They increase the plasma membrane surface area and are found on the surface of absorptive cells such as intestinal and kidney tubule cells.  Microvilli have a core of bundled actin filaments that extend into the terminal web of the cytoskeleton.  Actin is a contractile protein, but in microvilli it functions as a mechanical “stiffener.” MICROVILLI  Ciliary action  https://www.youtube.com/watch?v=xQG3QHM xoTA  Sperm action  https://www.youtube.com/watch?v=qz7uLX-A Olk  https://www.youtube.com/watch? v=_5OvgQW6FG4