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BIO 110 LECTURE | INTEGRATED PRINCIPLES OF BIOLOGY Professor Miriam De Vera Notes on Online Discussion Video 1 - September 11, 2024 Block 23, College of Public Health Made by: Prince Jehosaphat D. Villareal University of the Philippines Manila...

BIO 110 LECTURE | INTEGRATED PRINCIPLES OF BIOLOGY Professor Miriam De Vera Notes on Online Discussion Video 1 - September 11, 2024 Block 23, College of Public Health Made by: Prince Jehosaphat D. Villareal University of the Philippines Manila CELL MEMBRANE Introductory Lecture — Video Lesson 1 Organizational Structure — The following are the biological units of life from general to specific: Table 1: The Arrangement of the biological units of life 1. Biosphere 5. Organism 9. Cells 2. Biome 6. Organ 10. Cell 3. Ecosystem System Organelles 4. Population 7. Organs 11. Molecules 8. Tissues 12. Atoms — Cells are the most basic structural and functional units of life. GUIDE: Review each cell organelles! The Cell Membrane — The cell membrane is the physical barrier between Figure 2: The structure of a phospholipid the interior of the cell (cytoplasmic side) and the exterior — More spaces = more fluid of the cell (extracellular side). — More compacted = less fluidity — The commonly accepted model of the cell membrane is the fluid mosaic model. Fluidity of Membranes — Davson-Danielli model (1935): sandwich model - a — The phospholipids are not static, they are capable of phospholipid bilayer between two layers of proteins. movement (a membrane is held together primarily by — S. J. Singer and G. Nicolson (1972): membrane hydrophobic interactions) proteins reside in the phospholipid bilayer with their — The movement of phospholipids can be rapid (lateral) hydrophilic regions protruding. or slow (flip-flopping). — The plasma membrane is made up of lipids and proteins, as well as some carbohydrates. — The fluid in the fluid mosaic model is the lipids, while the embedded proteins are the “mosaics.” — The phospholipids are lipids that are unsaturated. They have a double bond in their tail, causing them to have “kinks” rather than straightly-defined tails. * A membrane remains fluid as temperature decreases until finally the phospholipids settle into a closely packed arrangement and the membrane solidifies. * The membrane remains fluid to a lower temperature if it is rich in phospholipids with unsaturated hydrocarbon Figure 1: The Plasma Membrane tails. — There is a double layer of phospholipids, denoting the fluid part of the model. — Cholesterol is present in between the hydrophobic — The cytoskeleton is mostly proteins. They provide tails of the phospholipids. They contribute to regulating structural support of the cell. the fluidity of the membrane depending on the — The predominant lipids of the phospholipid bilayer is temperature. the phospholipid (amphipathic). — With this, the steroid cholesterol acts as a fluidity buffer. Freeze-Fracture Technique Experiment: Science as a process. Membrane Proteins and their Functions — Demonstrates and provides evidence on how * Phospholipids form the main fabric of the membrane, proteins are arranged throughout the bilayer of the cell but proteins determine most of the membrane’s membrane. functions. — The bilayer is split apart then viewed in a scanning electron microscope. — Integral proteins penetrate the hydrophobic interior — Though we can’t see that these are rope-like at this of the lipid bilayer. Peripheral proteins are not particular resolution. embedded in the lipid bilayer at all. — The proteins are not blobs. They should be represented as ropes, chains, or codes. Any protein is a chain of amino acids. — The chain-like structure of proteins is called the alpha helical structure of proteins. — Cytoplasmic side: membrane proteins are held in Figure 3: The Freeze Fracture Technique place by attachment to the cytoskeleton. — Extracellular side: membrane proteins are attached to fibers of the extracellular matrix. Question: What is the difference between alpha helical structures and the “beta” structures? Table 2: The Components of the Cell Membrane and its Characteristics Component Composition Function How it works Phospholipid molecules Phospholipid bilayer Provides permeability Exclude water-soluble barrier, matrix for proteins. molecules from nonpolar interior of bilayer Transmembrane proteins Carrier Proteins Transport molecules across “Escorts” molecules the membrane against through the membrane by a concentration gradients. series of conformational changes. Channel Proteins Passively transport Having a hydrophilic molecules across the channel that certain e.g Aquaporins: passage membrane. molecules or atomic ions of water molecules use as a tunnel through the membrane. Receptors Transmit information into Signal molecules bind to the cell. the cell-surface portion of the receptor protein; this alters the portion of the receptor protein within the cell, inducing activity. Interior protein network Spectrins Determine shape of cell Form supporting scaffold beneath membrane, anchored to both the membrane and the cytoplasm. Clathrins Anchor certain proteins in Proteins line coated pits and specific sites, especially on facilitate binding to specific the exterior cell membrane molecules. in receptor-mediated endocytosis. Cell surface markers Glycoproteins “Self-recognition” Create a protein/carbohydrate chain shape characteristic of an individual. Glycolipids “Tissue recognition” Create a lipid/carbohydrate chain shape characteristic of a tissue. — One of the major functions of the cell membrane has because temperature increases the kinetic energy to deal with the transport of materials in and out of the (KE) of the solute. cell. (c) The electric charge, if any, of the diffusing — The cell is selectively permeable. SPM material: electric charge has a variable effect of (Selectively-permeable membrane). The transport diffusion. process might be passive or active; pertaining to an (d) The concentration gradient in the system—that energy input. is, the change in concentration with distance in a — The difference between these two is that passive given direction or the difference of the transport has no energy involved, while active transport concentration between the cytoplasmic side involves exchange of energy. and the extracellular side. The greater the concentration gradient, the more rapidly a PASSIVE TRANSPORT substance diffuses. — Molecules have a type of energy called thermal (e) The electrical charge of a solute particle—the energy (heat), due to their constant motion. membrane itself has its own charge. The solute — Movement of solute from a period of high particles’ permeability depends on the concentration to low concentration; moving along the difference between the charge of the solute concentration gradient. and the charge present in the membrane. — Has three types: diffusion, osmosis, and facilitated Greater difference between charges often diffusion. prevents the rate of diffusion of that charged — Does not require ATP phosphorylation. particle. The lesser the difference of the — Membrane proteins may or may not be present. electrical charges, diffusion can be more rapid. (f) The size of the solute also affects the rate of Diffusion diffusion. Smaller solute diffuses more across — Diffusion is the process in which solute particles the membrane. The hydrophobic components of move from an area of high concentration to an area the cell membrane will hinder the diffusion of of low concentration until it reaches equilibrium. big particles. — It is a flow of solute particles along the concentration gradient. It means it doesn’t need any energy and is Osmosis spontaneous, therefore it is a form of passive — Diffusion of free water across a selectively transport. permeable membrane, whether artificial or cellular. — The speed or rate of diffusion of a solute across the — Tonicity: ability of a surrounding solution to cause a semipermeable membrane will depend on these cell to gain or lose water. following factors: (a) The diameter of the molecules or ions: smaller Hypertonic, Hypotonic, and Isotonic Solutions molecules diffuse faster. Osmosis – Passive diffusion/transport (b) The temperature of the solution: higher temperatures lead to faster diffusion. It is — In an isotonic solution, there will be no net — The plant cell swells as water enters by osmosis. movement of water across the plasma membrane. — However, the relatively inelastic wall will expand Water diffuses across the membrane, but at the same rate only so much before it exerts a back pressure on the cell, in both directions. called turgor pressure, that opposes further water — In a hypertonic solution, cell shrinks as it will lose uptake. water, shrivel, and probably die. Turgid (very firm), which is the healthy state for — In a hypotonic solution, water will enter the cell most plant cells [hypotonic] faster than it leaves, and the cell will swell and lyse Flaccid (limp): plant’s cells and their (burst). surroundings are isotonic, there is no net tendency for water to enter [isotonic] Plasmolysis: lose water to its surroundings and shrink [hypertonic] Osmotic Pressure — Osmotic pressure is the force that would have to be applied to prevent solvent from moving across a semipermeable membrane due to concentration differences. Facilitated Diffusion *Hydrophobic substances are soluble in lipids and pass through membranes. * Whereas, polar molecules and ions impeded by the lipid bilayer of the membrane diffuse passively with the Figure 4: RBC in different NaCl concentrations help of transport proteins that span the membrane. — The kind of solute particles present in the given — There is an involvement of a membrane protein, solution is the electrolyte salt. specifically a channel protein and carrier protein. — There is also salt present inside the red blood cell. However, the cell membrane of the RBC is not permeable to NaCl but is permeable to water. Therefore the salt does not diffuse through. But water can pass through. — When solvent particles are often transported in passive transport processes, then it is called osmosis. — This is because there is a difference between the water potential in and out the cell. The water potential of the RBC is actually greater than the external solution, therefore water was lost in a hypertonic solution. — In a hypotonic solution, the water potential is greater than the solution outside the cell. — In plant cells, similar effects will be observed. *Channel proteins simply provide hydrophilic passageways that allow specific molecules or ions to cross the membrane. Figure 5: Plant Cell Osmosis — The plant cell is surrounded by a relatively rigid cell * Channel proteins that transport ions are called ion wall; the cell wall does not change its form in a channels (many are gated channels which open or hypertonic or a hypotonic solution. The plant cell wall is close in response to stimulus). primarily made of cellulose. — There are different types of channel proteins, one of — The presence of membrane proteins is a them are nonspecific transport proteins that serve as requirement. open gates for all solutes that have certain conditions (correct size, charge, etc) can pass through. E.g An animal cell has a much higher concentration of — Follows the concentration gradient. potassium ions (K ) and a much lower concentration of sodium ions (Na ). The plasma membrane helps maintain these steep gradients by pumping Na out of the cell and K into the cell. — ATP undergoes phosphorylation (ATP to ADP), energy input is required to drive the process. — Movement of solute against the concentration gradient (from a site of low concentration to high concentration). Figure 7: Nonspecific Transport Protein — There is also a presence of specific transporters. — Electrogenic pump: transport protein that generates voltage across a membrane. Figure 8: Specific Transport Proteins and Aquaporins (a) sodium-potassium pump: animal cells — (on the left) Only specific solutes can pass through (b) Proton pump: plants, fungi, and bacteria the protein. For instance, if a molecule is not a 6-carbon sugar ring, then it won’t pass through. — Specific transport proteins have something called a specificity. — For water molecules, there are proteins called aquaporins that are only specific to water. *Carrier proteins undergo a subtle change in shape that somehow translocates the solute-binding site across the membrane. ACTIVE TRANSPORT * Pump a solute across a membrane against its gradient requires work; the cell must expend energy. Figure 10: Tables comparing the transports, endocytosis, and exocytosis. — Vesicular transport uses vesicles engulfing matter into or outside the cell. — Vesicular transports are a form of active transport. — Exocytosis: particles go out of the cell; transport vehicles migrate to plasma membrane, fuse with it, and release contents. — There are two types of transport proteins used in active transport, namely; uniports and coupled transporters. — Endocytosis: particles enter the cell. * Cell takes in biological molecules and particulate matter by forming new vesicles from the plasma membrane. Figure 9: Uniport and Coupled Transport (a) phagocytosis (“cellular eating”) — Symport and Antiport types are called coupled (b) pinocytosis (“cellular drinking”) transporters. (c) receptor-mediated endocytosis VESICULAR TRANSPORT Bulk transport across the cell membrane Figure 11: Types of endocytotic processes. — (from Campbell’s Biology V4) In phagocytosis, pseudopodia engulf a particle and package it inside a vacuole (food or other solid particles). — In pinocytosis, droplets of extracellular fluid are incorporated into the cell by small vesicles (liquid particles in the extracellular fluid). — In receptor mediated endocytosis, coated pits form vesicles when specific molecules (ligands) bind to receptors on the cell’s surface. e.g Cholesterol travels in the blood in particles called low-density lipoproteins (LDLs), each a complex of lipids and a protein. LDLs (acting as ligands) bind to LDL receptors on plasma membranes and then enter the cells by endocytosis. Figure 12: Types of Antigens in blood CELL SURFACE MARKERS — The antigens here are called agglutinogens. — These are glycolipids or glycoproteins (carbohydrates — When a blood sample with type B comes into contact with proteins/lipids). with an Anti-B serum, or with Blood Type A. The cells would clump together or agglutinate. — No reaction would be observed vis-a-vis the same antigens. BIO 110 LECTURE | INTEGRATED PRINCIPLES OF BIOLOGY Professor Miriam De Vera Notes on Online Discussion Video 2 - September 11, 2024 Block 23, College of Public Health Made by: Prince Jehosaphat D. Villareal University of the Philippines Manila CELL SIGNALING 1 Introductory Lecture — Video Lesson 2 CELL TO CELL INTERACTIONS — Neurotransmitters are released from a nerve cell — Also referred to as intercellular communication or (source) to a pre-terminal nerve cell and then sent to cell to cell communication. another cell, may be a somatic cell or another nerve cell. — Crucial in a living organism, such as sorting cells to — Nerve cells are separated through a space called the tissues, and rejection of foreign cells (transplanted, synapse (synaptic cleft). Source and target cells are not immune, cancer cells). in direct contact. If there is a synapse involved in — It is possible for a cell to recognize another cell with transmission, then it is a neuronal signaling. the binding of surface molecules, often carbohydrates. — Glycolipid = carbohydrates to lipids — Glycoproteins = carbohydrates to membrane proteins SIGNAL MOLECULES TYPES OF CELL SIGNALING — The kind of signals that we are concerned with are molecules or chemical signals (cell signaling). Though signals can also be electrical (membrane potential). — Dependent on how far or the distance between the — Signal molecules may be water soluble. Because of source cell (sends the signal) and the target cell this, they cannot diffuse through cell membranes. This is (responds to the signal). because of the hydrophobic tails in the phospholipid (a) Direct contact: mechanism available for cells bilayer. that are adjacent to each other — For these water solubles to be able to trigger an - gap junctions, tight junctions, plasmodesmata appropriate cell response, they have to bind to the certain (b) Endocrine signaling: a signal is delivered from proteins inside the target cell. We can call these proteins a cell to another via the bloodstream (circulatory as receptor proteins (receiver of signaling molecules). system). The signal is delivered via the bloodstream because the cell is far apart. Cell signaling process: — In endocrine signaling, hormones are transported 1. Reception: detection of extracellular signaling and are required to be delivered via the bloodstream. molecule when the signal molecule binds to a receptor protein located at the surface or inside (c) Neuronal signaling: the passing of chemical the cell. Receptor proteins are specific (correct signals are in nerve cells. Though it may also signal molecule to binding site of protein). occur to other somatic cells, such as muscles. 2. Transduction: external signal is converted into a form that can bring about a specific cellular response. — This means that the signal molecule does not go into ligand exited the bonding site, the gate would close and the cell, but only initiates a series of reactions that alter ions would not be able to enter the cell anymore. the complexation of the protein inside the cell, a change in complexation triggers response. ENZYMIC RECEPTORS — There are specific proteins or molecules inside the — There are enzymes that are a component of the cell (relay molecules) that need to be activated. Once membrane proteins and are activated in the presence initiated by the signal molecule, the triggering of the of a signal molecule. Unless something binds, the response is induced (outcome). enzymes are inactive. — This may be referred to as a transduction pathway. 3. Response: any particular cellular activity that is the outcome of the transduction pathway. — Intracellular receptor proteins: can be found within the cytoplasm or the nucleus of the cell. These signaling molecules are lipid-soluble. They don’t need to bind to the membrane protein of the target cell. It can diffuse through the bilayer. (1) When signaling molecules bind to the receptor — Cell surface receptors are very specific. site of membrane protein, it activates the enzyme portion or catalytic domain. CHEMICALLY GATED ION CHANNELS * receptor tyrosine kinase should be a pair and will combine to form a dimer. — The dimer is just partially activated, it only becomes activated once there is an addition or phosphorylation of ATP to the tyrosine residues. — When fully activated, the relay proteins bind to the phosphorylated tyrosine residues then initiate the two cellular responses. — Ions are solute particles that can be transported into the cell membrane, but it is not easy. Infact, for the majority of charged particles, active transport is required. This is actually accomplished by the ion channels. — Ion channels are chemically gated. — Gated = can be opened or closed. — In order to open the “gate,” we need a key, therefore the key is the signal molecule or ligand. When the ligand binds to the receptor site of the membrane protein, the gate opens. Therefore allowing the passage * G protein (GTP [guanosine triphosphate] or GDP of ions in the interior of the cell. [guanosine diphosphate]) — Once the ions have entered the cell, the increase of * if GDP only is binded to G protein it will be inactive ions would result in a specific cellular response. If the SECOND MESSENGERS — Only works in GTP, doesn’t work in GDP. Therefore there should be a need for a complexation in the particular coupled receptor. — When the GDP is replaced by the GTP, the G-protein becomes active. When active, the G-protein will trigger an adjacent enzyme and activate it, causing a cellular — Chemical signal (primary messenger) is not lipid response. There might be a decomplexation of the soluble. It remains outside the cell but binds with initial receptor protein when the substrate debounds. appropriate membrane receptors. — Secondary messengers bind and activate target — When the G-protein binds to the enzyme, it is protein and lead to mediating cell response. dephosphorylated again (GTP bound to G-protein becomes dephosphorylated, GDP is left), deactivating * For Ca++, inositol triphosphate opens calcium ion the enzyme. The process will go again once a signaling channels increasing concentration of calcium ions in the molecule binds again into the coupled receptor. cytosol binding with target protein. e.g Glucose 6 Phosphatase is an enzyme that when Intracellular Receptors activated can catalyze the production of glucose molecules, most especially, in the cells of the kidney and in the liver and it can be distributed by the bloodstream towards different organs and tissues of the body, most especially the brain because glucose after all is the primary fuel that is needed for brain function. SIGNAL AMPLIFICATION — In this, the signaling molecule cortisol is lipid-soluble as they are in the nucleus (presence of DNA). — The arrival of the cortisol changes the complex of the receptor, releasing the inhibitor, therefore the domain of the receptor molecule is now free to bind with a specific DNA portion (gene) of the target cell to react. — Binding of the genetic region is understood as transcription or translation. — The protein that makes something more is called up-regulation, when something is decreased, then it is called down-regulation. — Chemical signal (ligand) complex to membrane the presence of a chemical signal, protein kinase, receptor which activates relay molecules and results in can phosphorylate (“on”) this molecule. amplification of signal. The result of the complementation is to activate not only just a single relay molecule, but more than 1. — Chemical signal (ligand) complex to membrane receptor which activates relay molecules and results in amplification of signal. The result of the complementation is to activate not only just a single relay molecule, but more than 1. *The necessary level or intensity of target cell response can still take place because of the cascading manner by which the different molecules in the transduction pathway can become activated. — Protein kinase adds the phosphate to turn on or switch SCAFFOLDING PROTEINS on the inactive protein while phosphatase will turn off or inactivate the protein by removing the phosphate. *extracts phosphate from ATP converting it to ADP (b) G-protein is inactive because GDP is linked. Addition of signal causes binding of GTP replacing GDP resulting in activation of protein. To turn off, GTP hydrolysis occurs by removing signaling molecules. COMMUNICATION AMONG MICROORGANISMS (1) Yeast cells — Scaffolding proteins do not actually activate any other substrate or any other substance in the transduction pathway. Their primary purpose is to relay molecules or relay proteins close to the cell membrane especially when you have the complexation of the signaling molecule to the receptor. — Scaffolding proteins (structural protein) have a binding site that attach different relay molecules together to deliver them to the signaling molecule and receptor complex, and initiate signal transduction. “More on a carrier not an activator” SIGNALING MOLECULES SERVING AS MOLECULAR SWITCHES — Signal transduction pathways, especially within a target cell, can serve as molecular switches to turn on or turn off the process that will result in a cell response. (a) Within the signal transduction pathway of a target cell, there is an inactive protein. However, * In order for these two types of mating cells to recognize one another they should have the appropriate membrane receptor for the mating factors. When those appropriate mating factors are present, they produce protrusions which are formed in the direction of the presence of the mating factors. *to move closer to source cells and perform reproduction (2) Myxobacteria (soil bacteria) * Individual bacterial cells send out signaling molecules to attract their neighbors so that they can gather closer to one another in order to form fruiting bodies and bacterial spores are formed to withstand unfavorable environmental conditions. — G-protein that is activated will result in the expression of your cyclic AMP (second messenger) — Intracellular communication with bacterial cells is leading to cell response of intestinal cells, opening the called quorum sensing. channel proteins for water and other ions. — G-protein that is activated will result in the expression of your cyclic AMP (second messenger) leading to cell response of intestinal cells, opening the channel proteins for water and other ions. *failure to close or switch off g-protein leads to diarrhea (3) Apoptosis — Programmed cell death (not necessarily bringing damage to nearby cells) BIO 110 LECTURE | INTEGRATED PRINCIPLES OF BIOLOGY Professor Miriam De Vera Notes on Online Discussion Video 2 - September 11, 2024 Block 23, College of Public Health Made by: Prince Jehosaphat D. Villareal University of the Philippines Manila MEMBRANE POTENTIAL Introductory Lecture — Video Lesson 3 MEMBRANE POTENTIAL — difference in electric charge (voltage of ions) between GATED ION CHANNELS interior and exterior of cell membrane. (-60 mV) — a channel that opens or closes in response to a shift in the voltage across the plasma membrane of the RESTING POTENTIAL / EQUILIBRIUM neuron. POTENTIAL — voltage present when cell is “unstimulated” The sodium-potassium pump uses the energy of ATP (a) Hyperpolarization hydrolysis to actively transport Na+ out of the cell and (more negative) K+ into the cell. results from any stimulus that increases the outflow of positive ions or the inflow of negative ions. —The concentration of Na+ is higher outside than inside; the reverse is true for K+. In resting neurons, the plasma membrane has many open potassium channels but few open sodium channels. Diffusion of ions, (b) Depolarization principally K+, through channels generates a resting (more positive) potential, with the inside more negative than the outside. if a stimulus causes gated sodium channels to open, the membrane’s permeability to Na+ increases. * Graded potential: induce a small electrical current that dissipates as it flows along the membrane. (c) Action Potential change in voltage when stimulated and depolarization that reaches threshold. REFRACTORY PERIOD — “downtime” when a second action potential cannot be initiated due to the inactivation of sodium channels CONDUCTION OF ACTION POTENTIALS — At the axon hillock, Na+ inflow during the rising phase creates an electrical current that depolarizes the neighboring region of the axon membrane. — An action potential is an all-or-none event, the magnitude and duration of the action potential are the same at each position along the axon. MYELIN SHEATH — produced by glia: oligodendrocytes in the CNS and ELECTRICAL SYNAPSES Schwann cells in the PNS. — contain gap junctions that allow electrical current to flow directly from one neuron to another. — membranes forming these layers are mostly lipid, which is a poor conductor of electrical current and thus a * synaptic vesicles: membrane-enclosed compartments good insulator. * synaptic cleft: gap that separates the presynaptic neuron from the postsynaptic cell * Action potentials propagate more rapidly in myelinated axons because the time-consuming process of opening POSTSYNAPTIC POTENTIAL and closing of ion channels occurs at only a limited — receptor protein that binds and responds to number of positions along the axon. neurotransmitters is a ligand-gated ion channel, often called an ionotropic receptor — Saltatory conduction: action potential appears to — a graded potential in the postsynaptic cell. jump from node to node along the axon. (a) Endorphins: natural analgesics, decreasing pain perception Excitatory postsynaptic Inhibitory postsynaptic potential (EPSP) potential (IPSP) depolarization hyperpolarization NEUROTRANSMITTERS — Acetylcholine: muscle stimulation, memory formation, and learning — Amino Acids: (a) Glutamate: neurotransmitter (CNS) *formation of long term memory (b) Glycine: inhibitory (c) gamma-aminobutyric acid (GABA): inhibitory — Biogenic amines: synthesized from amino acids and include norepinephrine, which is made from tyrosine. (a) Epinephrine (b) Dopamine (c) Serotonin — Neuropeptides: neurotransmitters that operate via G protein-coupled receptors.

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