GENERAL PHYSIOLOGY NOTES PRELIMS.pdf

GENERAL PHSYIOLOGY NOTES PRELIMS 1. Principles of Cell Theory First Principle: All living organisms are made up of one or more cells. Second Principle: Cells are the basic structural and organizational unit of life. Third Principle: All cells arise from pre-existing cells via pro...

GENERAL PHSYIOLOGY NOTES PRELIMS 1. Principles of Cell Theory First Principle: All living organisms are made up of one or more cells. Second Principle: Cells are the basic structural and organizational unit of life. Third Principle: All cells arise from pre-existing cells via processes like cell division (mitosis or meiosis). 2. Universal Features of Cells Regardless of type, all cells share these basic features: Cell Membrane: Separates the interior of the cell from the external environment. Cytoplasm: Jelly-like substance where cell components are suspended. DNA: Genetic material that carries instructions for cell function and reproduction. Ribosomes: Synthesize proteins required for cell function. 3. Types of Cells Prokaryotic Cells: Characteristics: Simple cells without a nucleus; DNA is circular and found in the nucleoid. Examples: Bacteria and archaea. Cell Wall: Provides protection and structure. Reproduction: Rapid division through binary fission. Significance: Ancient life forms; key in the evolution of life and symbiotic relationships. Size and Complexity: Smaller and simpler compared to eukaryotes. Eukaryotic Cells: Characteristics: Complex cells with a nucleus and membrane-bound organelles. Organelles: Mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes. Reproduction: ○ Mitosis: Produces two identical daughter cells. ○ Meiosis: Creates sex cells with half the number of chromosomes. Endosymbiotic Theory: Suggests mitochondria and chloroplasts evolved from prokaryotes. Size and Complexity: Larger and more complex; can be unicellular or multicellular. Examples: Plant, animal, fungal, and protist cells. 4. Animal and Plant Cells Animal Cells: Nucleus: Contains DNA and controls cell functions. Mitochondria: Generate energy (ATP) through cellular respiration. Endoplasmic Reticulum (ER): ○ Rough ER: Processes proteins, has ribosomes attached. ○ Smooth ER: Synthesizes lipids, detoxifies chemicals. Golgi Apparatus: Modifies and packages proteins and lipids for transport. Lysosomes: Break down waste and debris with enzymes. Centrioles: Organize the separation of chromosomes during cell division. Vacuoles: Store nutrients and waste (smaller than in plant cells). Plant Cells: Nucleus: Controls cell functions and holds DNA. Mitochondria: Produce energy (ATP) like in animal cells. Chloroplasts: Use sunlight to perform photosynthesis (produce glucose), contain chlorophyll. Cell Wall: Provides structural support, made of cellulose. Central Vacuole: Large, stores water, nutrients, and waste, and helps maintain cell shape. Key Differences: Chloroplasts: Present only in plant cells for photosynthesis. Cell Wall: Present in plant cells, absent in animal cells. Central Vacuole: Larger in plant cells for storage and maintaining shape. 5. Important Organelles and Their Functions Nucleus: Contains DNA and regulates cell activities, including protein synthesis. Mitochondria: Known as the "powerhouse," they generate ATP, the energy currency of the cell. Endoplasmic Reticulum (ER): ○ Rough ER: Site of protein synthesis due to attached ribosomes. ○ Smooth ER: Involved in lipid synthesis and detoxification. Ribosomes: Carry out protein synthesis. Can be: ○ Free ribosomes: Floating in the cytoplasm, synthesize proteins for the cell’s own use. ○ Bound ribosomes: Attached to the rough ER, synthesize proteins for export or membrane insertion. Golgi Apparatus: Processes and packages proteins and lipids for transport within or outside the cell. Lysosomes: Contain digestive enzymes to break down waste materials and foreign invaders. Centrosomes/Centrioles: Help organize microtubules during cell division. Peroxisomes: Break down fatty acids and detoxify harmful substances. 6. Cellular Energy and Reactions ATP: The energy currency of the cell, composed of adenine, ribose sugar, and three phosphate groups. Photosynthesis: Plants and algae convert sunlight into glucose, releasing oxygen as a byproduct. Energy Cycling: Energy flows and cycles through living organisms, with chemicals being continuously recycled. Coupled Reactions: Energy released in one reaction is used to drive another reaction forward. 7. Specialized Cells and Functions Axons & Dendrites: Specialized in nerve cells to transmit signals. Microvilli & Cell Junctions: Maintain barrier functions in epithelial tissues. Sarcomere: Muscle cell structure responsible for contraction. 8. Function and Structure of Ribosomes Ribosomes: Play a critical role in translating genetic information from mRNA into proteins. Types: ○ Free Ribosomes: Produce proteins that remain within the cell. ○ Bound Ribosomes: Produce proteins that are exported or inserted into the cell membrane. Structure: Composed of two subunits (large and small) that come together during translation. Function: Facilitate protein synthesis through initiation, elongation, and termination phases of translation. 9. Evolutionary Significance Prokaryotes: Among the earliest life forms on Earth. Play a key role in evolutionary history and symbiotic relationships. Capable of surviving in extreme environments with diverse metabolic processes. Eukaryotes: Evolved to form complex, multicellular organisms.  Display greater cellular specialization and complexity, leading to the development of plants, animals, fungi, and protists. Endosymbiotic Theory: Explains the origin of mitochondria and chloroplasts through the engulfment of prokaryotic organisms. Cell Membrane and Membrane Potential Overview The cell membrane is a dynamic structure essential for maintaining the integrity and functionality of the cell. It controls what enters and exits the cell, enabling communication, transport, and cellular homeostasis. The cell membrane’s architecture and functions are crucial for the generation of membrane potential, which plays a vital role in neuronal signaling and action potentials. 1. Cell Membrane Structure and Function The cell membrane is composed of a phospholipid bilayer, with hydrophilic heads facing outward and hydrophobic tails inward, forming a selective barrier. This arrangement makes the membrane selectively permeable, allowing only certain molecules to pass through. Key Functions: Compartmentalization: It separates the cell’s interior from its external environment. Selective Permeability: Controls the movement of ions, nutrients, and waste products. Membrane Proteins: ○ Transport Proteins: Assist in moving substances, like ions, across the membrane (e.g., sodium, potassium). ○ Ion Channels: Allow ions like sodium (Na⁺) and potassium (K⁺) to pass, crucial for nerve signaling. ○ Carrier Proteins: Help transport larger molecules, like glucose, across the membrane. 2. Transport Across the Membrane The cell membrane controls substance movement using passive transport (no energy required) and active transport (energy required). Passive Transport: ○ Simple Diffusion: Movement of small molecules like oxygen. ○ Facilitated Diffusion: Uses transport proteins for larger molecules. ○ Osmosis: Water moves across the membrane through aquaporins. Active Transport: ○ Primary Active Transport: Uses ATP to pump ions against their concentration gradient, such as the sodium-potassium pump (Na⁺ out, K⁺ in). ○ Vesicular Transport: Large molecules are moved via endocytosis (into the cell) and exocytosis (out of the cell). 3. Membrane Potential and Ion Distribution Membrane potential refers to the difference in electrical charge between the inside and outside of the cell, primarily maintained by ion concentration gradients and selective ion permeability. Key Ions: Sodium (Na⁺): More prevalent outside the cell. Potassium (K⁺): More prevalent inside the cell. Chloride (Cl⁻): More outside the cell. Organic Anions: Large, negatively charged molecules inside the cell. At rest, the cell’s membrane potential is about -70 millivolts (mV), with the inside of the cell being more negatively charged compared to the outside. This state is known as the resting membrane potential. 4. Sodium-Potassium Pump and Resting Membrane Potential The sodium-potassium pump (Na⁺/K⁺ pump) is a critical mechanism that maintains the resting membrane potential: It pumps 3 sodium ions (Na⁺) out of the cell and 2 potassium ions (K⁺) in, using ATP. This creates an electrochemical gradient where the outside is more positive, and the inside is more negative, resulting in the resting potential of around -70 mV. Additionally, potassium ion channels allow K⁺ to move freely, helping maintain the potential by balancing the charge distribution. 5. Action Potential: Electrical Signaling in Neurons An action potential is a rapid and temporary change in the membrane potential that allows neurons to send electrical signals. It is a key feature of neuronal communication. Stages of an Action Potential: 1. Resting State: The neuron is at -70 mV, with sodium ions outside and potassium ions inside. 2. Depolarization: A stimulus causes sodium channels to open, allowing Na⁺ to flow into the cell, making the inside more positive. The membrane potential becomes less negative and reaches the threshold potential (around -55 mV). 3. Rising Phase: Once the threshold is crossed, more sodium channels open, causing a rapid influx of Na⁺. This depolarization brings the membrane potential to a positive value, usually around +30 mV. 4. Repolarization: Sodium channels close, and potassium channels open. K⁺ ions exit the cell, restoring the membrane potential to a negative value. 5. Hyperpolarization: The membrane potential briefly becomes more negative than the resting potential due to the continued efflux of K⁺, reaching around -80 mV. This is followed by the closure of potassium channels. 6. Refractory Period: During hyperpolarization, the neuron cannot fire another action potential. The cell eventually returns to its resting state, ready to fire again. 6. Neurotransmission and Communication The action potential travels along the neuron to the axon terminals, where it triggers the release of neurotransmitters. These chemicals cross the synapse to stimulate the next neuron, continuing the signal or causing other actions like muscle contractions. Summary Cell Membrane: The selectively permeable phospholipid bilayer that controls what enters and exits the cell, involving transport proteins, ion channels, and active/passive transport mechanisms. Membrane Potential: The electrical charge difference between the inside and outside of a cell, primarily maintained by the sodium-potassium pump and ion distribution. Resting Potential: The stable negative charge of a cell at rest (~-70 mV), crucial for action potentials. Action Potential: A rapid reversal of the membrane potential that allows neurons to communicate electrically, vital for nerve function. CENTRAL DOGMA The central dogma of molecular biology explains how genetic information flows within a biological system to produce proteins. It involves three main processes: 1. DNA Replication: ○ Description: DNA replication creates an identical copy of DNA, crucial for cell division. ○ Process: Unwinding: The DNA double helix separates into two single strands. Complementary Base Pairing: Each strand serves as a template for a new complementary strand. DNA polymerases add nucleotides to form new strands (A pairs with T, C with G). Formation of New Strands: Two new DNA molecules are formed, each with one original strand and one new strand, ensuring accurate copying.  2. Transcription: ○ Description: Transcription converts a segment of DNA into messenger RNA (mRNA), which carries the genetic code to the ribosomes for protein synthesis. ○ Process: Initiation: RNA polymerase binds to the gene's promoter region, unwinding the DNA. Elongation: RNA polymerase reads the DNA and synthesizes a complementary RNA strand, using uracil (U) instead of thymine (T). Termination: Transcription ends at a termination signal, releasing the mRNA, which is processed (e.g., capping, polyadenylation, splicing) before leaving the nucleus. 3. Translation: ○ Description: Translation assembles a polypeptide (protein) using the mRNA sequence at the ribosome. ○ Process: Initiation: The mRNA binds to a ribosome, starting at the start codon (usually AUG). Transfer RNA (tRNA) molecules with complementary anticodons and amino acids bind to the mRNA. Elongation: The ribosome moves along the mRNA, tRNAs bring amino acids, and peptide bonds form between them, creating a growing polypeptide chain. Termination: Translation ends at a stop codon, releasing the completed polypeptide and dissociating the ribosome and mRNA. Summary: DNA Replication: Copies genetic information for cell division. Transcription: Converts DNA into mRNA, carrying the code to ribosomes. Translation: Uses mRNA to build proteins, translating genetic information into functional molecules. These processes ensure genetic information is preserved, expressed, and used to produce proteins essential for cellular function and development. 1. Catabolism and Anabolism Connection: Catabolic reactions generate energy, which anabolic reactions use to build molecules. 2. Pyruvate Carbon Atoms in Pyruvate: Each pyruvate molecule contains 3 carbon atoms. 3. ATP in Glycolysis ATP Energy Storage: ATP stores energy in the high-energy bonds between phosphate groups. 4. Low Blood Glucose Suggestion Recommendation: Suggest drinking a maltose sports drink (a disaccharide of two glucose molecules). 5. Aerobic vs. Anaerobic Respiration Aerobic Respiration: Requires oxygen. Anaerobic Respiration: Does not require oxygen. 6. Krebs Cycle Net Result (Per Glucose) Products: 8 NADH, 2 FADH2, 2 ATP, and 6 CO2 molecules. 7. Importance of the Krebs Cycle Why Important: Produces reducing agents (NADH and FADH2) essential for the electron transport chain (ETC). 8. Oxidative Phosphorylation Two Coupled Processes:  ○ Oxidation of electron carriers (NADH and FADH2). ○ Phosphorylation of ADP to produce ATP. 9. Measuring Cellular Respiration Experimental Parameters: Measure various options such as oxygen consumption, CO2 production, and ATP levels to assess the effect of exercise on cellular respiration in mice. 10. Oxygen in Cellular Respiration Role: Acts as the final electron acceptor in the electron transport chain, facilitating ATP production. 11. Effect of Exercise on Oxygen Consumption During Exercise: Oxygen consumption will increase as cells demand more energy. 12. Extreme Exercise Experiment Test Conditions: Make the mouse run at high speed under low oxygen availability. 13. ATP Yield in Low Oxygen (Anaerobic Conditions) ATP Yield: 2 ATP molecules from glycolysis. 14. Basic Conversions 1 dl = 100 ml. 15. Glycolysis Glucose Conversion: One glucose molecule (6 carbon) is converted into 2 pyruvate (each with 3 carbon atoms). 16. Maltose Disaccharide: Consists of glucose + glucose. 17. CO2 Production 6 CO2 Molecules: Contain 6 carbon atoms. 18. Oxidation and Reduction Oxidation: Loss of electrons. Reduction: Gain of electrons. 19. Pyruvate Without Oxygen Anaerobic Conditions: Pyruvate is converted into lactic acid. 20. ATP Yield from the Electron Transport Chain ETC Produces: 34 ATP molecules. 21. Fermentation Glycolysis: Yes, fermentation involves glycolysis. 22. NADH Oxidation NADH is oxidized to: NAD+. 23. Aerobic vs. Anaerobic Respiration Steps Anaerobic Respiration: Does not include the electron transport chain (ETC), which is present in aerobic respiration. Motor Unit Recruitment in Skeletal Muscle Overview: Motor units consist of a single motor nerve and all the muscle fibers it innervates. A single motor nerve can activate 500 to 1,000 muscle fibers, illustrating the extensive relationship between nerve and muscle fibers. The "all or none" principle means that when a motor nerve fires, all associated muscle fibers contract simultaneously; when the nerve stops firing, the muscles cease to contract. Motor Unit Recruitment: Order of Recruitment: ○ Light Load: Activates primarily Type 1 motor units (slow-twitch fibers). These fibers are recruited first due to their efficiency in low-intensity activities. ○ Moderate Load: Involves Type 2a motor units (fast-twitch oxidative fibers), with Type 1 fibers still contributing. Type 2a fibers are recruited as the load increases to handle more force. ○ Heavy Load: Engages Type 2x motor units (fast-twitch glycolytic fibers), with Type 1 and Type 2a fibers also contributing. Type 2x fibers are recruited to manage high-intensity loads due to their larger diameter and greater force production. Factors Influencing Recruitment: Motor unit recruitment is influenced by the load or force required. As the load increases: ○ Type 1 fibers are recruited first. ○ Type 2a fibers are recruited for moderate loads. ○ Type 2x fibers are recruited for heavy loads, with Type 1 and Type 2a fibers assisting. Skeletal Muscle Contraction Part 1 Overview: Muscle contraction involves two major proteins: actin and myosin. Myosin has head structures (S1 units) that bind ATP and contain ATPase enzymes for muscle action. Actin is a double helix molecule, with tropomyosin and troponin proteins associated with it. Protein Structures: Myosin: A double helix molecule with S1 units where ATP binds and ATPase is active. Actin: Also a double helix, with tropomyosin (a rope-like protein) and troponin (a protein complex with three components). ○ Tropomyosin covers actin's binding sites in a resting muscle state. ○ Troponin binds to tropomyosin and shifts with it. Muscle Contraction Mechanism: 1. Calcium Release: ○ Calcium ions are released from the sarcoplasmic reticulum (SR) and bind to troponin. ○ This binding causes a strong reaction that shifts tropomyosin, exposing binding sites on actin. 2. ATP Role: ○ ATP splits into ADP + inorganic phosphate + energy via ATPase on S1 units. ○ This energy allows the S1 units of myosin to bind to the exposed sites on actin. 3. Power Stroke: ○ The binding of myosin to actin leads to a power stroke, where ADP and inorganic phosphate are released, and actin slides over myosin. ○ This movement, known as the power stroke, is a highly efficient mechanism that has evolved over millions of years. 4. Release and Reset: ○ A fresh ATP molecule binds to the S1 units, causing them to detach from actin. ○ The cycle then repeats with calcium ions being pumped back to the SR when the nerve signal stops, and tropomyosin covers the binding sites again. Review Points:  Calcium Ions: Released from the SR, bind to troponin. Troponin: Binds to tropomyosin; shifts it to expose binding sites on actin. ATP and ATPase: ATP splits into ADP and inorganic phosphate; ATPase enzyme aids this process. Power Stroke: Actin slides over myosin, resulting in muscle contraction. Disconnection: Fresh ATP causes myosin to release from actin. Skeletal Muscle Contraction Part 2 Overview of the Neuromuscular Junction Neuromuscular Junction: The site where the motor neuron communicates with the muscle fiber. Sarcolemma: Plasma membrane of the muscle fiber; polarized. Motor End Plate: The region of the sarcolemma that interacts with the axon terminal; features folds for efficient neurotransmission. T-Tubules (Transverse Tubules): Invaginations of the sarcolemma that transmit the depolarization signal into the muscle fiber. Depolarization and Calcium Release 1. Acetylcholine (ACh): Neurotransmitter released at the neuromuscular junction. 2. Exocytosis: Process by which ACh is released from synaptic vesicles into the synaptic cleft. 3. Ion Channels: Ligand-gated ion channels on the motor end plate open in response to ACh, allowing sodium (Na⁺) to enter the muscle fiber. 4. Depolarization: The influx of Na⁺ causes the sarcolemma and T-tubules to become depolarized. 5. Calcium Ions (Ca²⁺): Released from the sarcoplasmic reticulum (SR) into the muscle fiber upon excitation by T-tubules. Sequence of Events 1. Impulse Arrival: Action potential reaches the axon terminal. 2. Calcium Influx: Calcium ions enter the axon terminal. 3. Synaptic Vesicle Fusion: Vesicles fuse with the nerve cell membrane, releasing ACh. 4. ACh Binding: ACh binds with receptors on the motor end plate. 5. Depolarization of Motor End Plate: Leads to an action potential traveling along the sarcolemma. 6. Transmission via T-Tubules: Action potential moves into the muscle fiber via T-tubules. 7. Calcium Release: T-tubules excite the SR to release Ca²⁺. 8. Muscle Contraction: Ca²⁺ binds to troponin, causing tropomyosin to shift and allowing contraction. Muscle Fiber Types Fast Twitch Fibers: Generate more force but fatigue quickly. Slow Twitch Fibers: More resistant to fatigue; type I fibers (slow oxidative). Calcium's Double Role 1. Neurotransmitter Release: Calcium reacts with synaptic vesicles to release ACh. 2. Contraction Mechanism: Calcium binds with troponin, shifting tropomyosin and enabling contraction. Proprioceptors Muscle Spindles: Sense stretch and the speed of stretch in a muscle. They protect against overstretching by sending messages to the spine. Golgi Tendon Organs: Located in tendons; sense tension and protect against excessive force by sending signals to the spinal cord and cerebral cortex. Key Terminologies Sarcolemma: Plasma membrane of muscle fibers. Motor End Plate: Area of sarcolemma at the neuromuscular junction. T-Tubules: Extensions of the sarcolemma into the muscle fiber. Acetylcholine (ACh): Neurotransmitter involved in muscle contraction. Exocytosis: Release of neurotransmitters from synaptic vesicles. Ligand-Gated Ion Channels: Receptors that open in response to ACh binding.  Sarcoplasmic Reticulum (SR): Organelle that releases Ca²⁺ in response to T-tubule stimulation. Troponin: Protein that binds calcium to regulate muscle contraction. Tropomyosin: Protein that blocks the binding sites on actin when the muscle is relaxed. Proprioceptors: Sensory receptors that monitor muscle and tendon conditions. Muscle Contraction and Structure Overview Thick and Thin Filaments Muscle Contraction occurs at the microscopic level within the sarcomere. Sliding Filament Mechanism: 1. Actin (thin) filaments slide along the myosin (thick) filaments. 2. Z lines, which form the boundaries of the sarcomere, move closer together, causing the muscle to shorten, resulting in contraction. Muscle Cell Parts 1. Sarcolemma: The membrane surrounding a muscle cell. 2. Sarcoplasm: The cytoplasm of a muscle cell. 3. Sarcoplasmic Reticulum: An organelle in the muscle cell responsible for storing and releasing calcium ions (Ca²⁺), essential for muscle contraction. Sarcomere Structure 1. Z Lines: Define the boundaries of each sarcomere. 2. I Band: The region containing only actin (thin filaments). 3. H Zone: The region containing only myosin (thick filaments). 4. A Band: The region where actin and myosin overlap. 5. M-Line: The midpoint of the sarcomere, where myosin filaments are anchored. Muscle Contraction Process (10 Steps) 1. A nerve impulse arrives at the presynaptic terminal of the neuromuscular junction. 2. This impulse triggers the release of acetylcholine (Ach) from synaptic vesicles in the axon terminal. 3. Ach diffuses across the synaptic cleft, opening sodium (Na⁺) channels in the muscle membrane. 4. Sodium ions enter the muscle cell, causing depolarization. 5. The impulse travels through the T-tubules, leading to the release of calcium ions (Ca²⁺) from the sarcoplasmic reticulum. 6. Calcium ions bind to troponin on the tropomyosin strands, causing the tropomyosin to move and expose binding sites on the actin filaments. 7. Myosin heads bind to the exposed sites on the actin filaments, forming crossbridges. 8. ATP binds to myosin, breaking down to release energy, causing the myosin to pull the actin filaments. 9. Another ATP molecule binds to myosin, allowing it to release, re-cock, and reattach to actin for the next "power stroke." 10. When the action potential ends, Ca²⁺ is pumped back into the sarcoplasmic reticulum, tropomyosin covers the binding sites, and muscle relaxation occurs. Role of Calcium in Muscle Contraction 1. Calcium binds to the troponin complex on the actin filaments. 2. This binding causes tropomyosin to move, exposing the binding sites on the actin filaments. 3. The exposed sites allow the myosin heads (from the thick filaments) to bind to the actin, initiating contraction. HOMEOSTASIS 1. Definition of Homeostasis Homeostasis is the process by which living organisms maintain stable internal conditions, even when external conditions change. It regulates things like body temperature, pH levels, and blood glucose, ensuring that they stay within safe limits.  Systems like the nervous and endocrine systems help coordinate the body’s response to internal and external changes. 2. How Homeostasis is Achieved Homeostasis works through feedback loops: ○ Sensors detect changes in the environment (e.g., high body temperature). ○ The control center (usually the brain) processes the information and decides on a response. ○ Effectors (like glands or muscles) carry out the necessary action (e.g., sweating to cool the body). There are two types of feedback: ○ Negative feedback: Reduces the effect of a change (e.g., cooling down when overheated). ○ Positive feedback: Enhances the effect of a change (e.g., blood clotting). 3. Consequences of Failure in Homeostasis When the body can’t maintain homeostasis, it can lead to disorders or even death. ○ For example, failure to regulate body temperature can lead to heat stroke or hypothermia. ○ If blood sugar levels are not controlled, it can result in diabetes, affecting energy levels and overall health. FEEDBACK LOOPS Feedback loops are essential mechanisms that help biological systems maintain homeostasis, or a stable internal environment. These loops involve processes where the product of an action influences the system, either amplifying or inhibiting that action. Feedback loops can be classified into two main types: positive feedback loops and negative feedback loops. Positive Feedback Loops A positive feedback loop amplifies changes in a system, driving the system further from equilibrium. It reinforces the outcome of an event, often leading to a rapid response. Examples of Positive Feedback: 1. Fruit Ripening: When an apple ripens, it emits ethylene gas, which causes nearby apples to ripen, creating a cascading effect until all fruit ripens together. 2. Childbirth: During labor, pressure on the cervix triggers the release of oxytocin, which intensifies contractions, leading to more oxytocin release until the baby is born. 3. Blood Clotting: When a wound occurs, activated platelets release chemicals that signal more platelets to come, amplifying the process until the clot forms. Negative Feedback Loops A negative feedback loop reduces or counteracts changes, helping to stabilize a system by bringing it back to a target state or equilibrium. Examples of Negative Feedback: 1. Temperature Regulation: When the body gets too hot, it sweats to cool down. When it gets too cold, it shivers to generate heat, maintaining the body's ideal temperature. 2. Blood Pressure Regulation: Baroreceptors in the arteries detect changes in blood pressure. If it's too high or low, signals are sent to the heart to adjust the rate and strength of contractions. 3. Osmoregulation: In saltwater fish, the regulation of salt levels helps the organism maintain a balance of salt and water, ensuring homeostasis. Positive vs. Negative Feedback Positive feedback pushes a system away from its normal state, leading to quick and often temporary changes. Negative feedback stabilizes a system, keeping it closer to equilibrium and maintaining a steady state. Importance of Feedback Loops Feedback loops are critical for biological processes because they ensure organisms can adapt to their environment and maintain homeostasis. Without feedback, systems would be unable to regulate internal conditions, leading to disorders or failure to survive. For instance, in diabetes, the negative feedback loop regulating blood sugar breaks down, leading to dangerously high blood glucose levels. REFLEX ACTION 1. Reflex Arc vs. Reflex Action Reflex Arc: The pathway through which a reflex occurs. It includes: 1. Sensory Receptor: Detects the stimulus. 2. Sensory Neuron: Carries the signal to the spinal cord. 3. Interneuron: Processes the signal. 4. Motor Neuron: Sends a command to the effector. 5. Effector: The muscle or gland that reacts. Reflex Action: The actual involuntary response to a stimulus. It happens automatically and quickly, without thinking, like pulling your hand away from a hot surface. 2. Importance of Reflex Actions Reflexes protect the body from danger by providing fast responses to harmful stimuli. They also regulate essential functions, like blinking to protect the eyes or maintaining blood pressure. These automatic reactions ensure survival by allowing the body to act instantly. PHENOTYPIC PLASTICITY 1. What is Phenotypic Plasticity? Phenotypic plasticity is the ability of a single genotype (genetic makeup) to produce different phenotypes (observable traits) in response to environmental changes. An example is the astronaut Scott Kelly, whose gene expression changed after spending time in space compared to his twin brother on Earth. This adaptability helps organisms survive in different environments by adjusting their traits (like body shape or behavior) depending on conditions like temperature or available food. 2. Polyphenism vs. Polymorphism Polyphenism: A form of phenotypic plasticity where the environment triggers the development of different forms. For example: ○ Caterpillars of the Nemoria arizonaria moth: In spring, they look like catkins, but in summer, they resemble twigs. ○ Ant castes: Nutrition and environment determine whether an ant becomes a worker, soldier, or queen. Polymorphism: Genetic variation within a population, where different traits are passed down through generations. For example: ○ Peppered moths: They come in two forms—light and dark—based on environmental factors like pollution. ○ Human blood types: The ABO system is an example of genetic polymorphism with types A, B, AB, and O. Cell Signaling Cell signaling is a complex process that allows cells to communicate and respond to their environment through a series of biochemical reactions. This process can be divided into several stages, from ligand binding to a receptor, signal transduction, and cellular responses. Stages of Cell Signaling:  1. Ligand Binding: ○ Cell signaling begins when a ligand (such as a hormone or neurotransmitter) binds to a specific receptor on the cell membrane. One such example is epinephrine, which binds to a G-protein coupled receptor (GPCR). GPCRs are embedded in the cell membrane and play a crucial role in detecting extracellular signals and transmitting them inside the cell. 2. Activation of G-Protein: ○ Upon binding of epinephrine, the GPCR undergoes a conformational change that activates the associated G-protein. G-proteins consist of three subunits: alpha, beta, and gamma. Once activated, the alpha subunit dissociates from the beta and gamma subunits. The specific alpha subunit of the G-protein then interacts with an effector enzyme, adenylyl cyclase. 3. Adenylyl Cyclase Activation and cAMP Production: ○ Adenylyl cyclase is activated by the binding of the alpha subunit of the G-protein to it. This enzyme catalyzes the conversion of ATP (adenosine triphosphate) into cAMP (cyclic adenosine monophosphate). For every 4 molecules of ATP, 4 cAMP molecules are produced, releasing 8 phosphate groups in the process. cAMP serves as a second messenger, amplifying the signal within the cell and initiating a cascade of intracellular events. 4. Signal Transduction: ○ Once cAMP is generated, it initiates the transduction process, where multiple downstream signaling molecules become activated. One common pathway involves the activation of protein kinases, such as protein kinase A (PKA), which phosphorylate other proteins, leading to changes in cellular functions. These effects can include alterations in metabolism, gene expression, or structural changes in the cell. 5. cDNA Synthesis from Reverse Transcriptase: ○ In some cell signaling pathways, the signal may lead to changes in gene expression. For instance, when reverse transcriptase is involved, cDNA (complementary DNA) can be synthesized from mRNA, allowing the cell to produce specific proteins in response to the signaling event. Signal Transduction Signal transduction refers to the series of processes by which an extracellular signal is converted into a functional cellular response. The key components of this process include various types of receptors and signaling molecules that facilitate communication within the cell. Types of Receptors in Signal Transduction: 1. Intracellular Receptors: ○ These receptors are located inside the cell and respond to signaling molecules that can cross the cell membrane, such as steroid hormones. When a signaling molecule binds to an intracellular receptor, it often results in changes to gene expression by directly interacting with the cell’s DNA. This leads to the production of proteins that alter cellular functions. 2. Ligand-Gated Ion Channels: ○ These receptors are found on the cell membrane and change shape when a ligand binds, allowing ions to flow into or out of the cell. The influx of ions, such as sodium or calcium, alters the cell’s electrical charge and can trigger various cellular responses, such as in neurons where ligand-gated ion channels are involved in neurotransmission. 3. Receptor Enzymes: ○ One important class of receptor enzymes is receptor tyrosine kinases (RTKs), which possess intrinsic enzymatic activity. When a ligand binds to RTKs, it triggers a phosphorylation cascade, where the receptor and other proteins are phosphorylated, initiating various downstream signaling pathways. These phosphorylation events regulate numerous cellular processes, including cell growth and differentiation. 4. G-Protein Coupled Receptors (GPCRs): ○ GPCRs, such as those that respond to epinephrine, play a pivotal role in cell signaling. When a ligand binds to a GPCR, it activates the associated G-protein. As discussed earlier, the alpha subunit of the G-protein activates adenylyl cyclase, leading to the production of cAMP from ATP. This cAMP acts as a second messenger, propagating the signal inside the cell and activating various downstream pathways, including the phosphorylation of proteins by kinases. Types of Signaling  1. Endocrine Signaling: ○ Involves hormones traveling through the bloodstream to target distant cells. Lipophilic hormones (e.g., steroid hormones) can cross the cell membrane and interact with intracellular receptors, while water-soluble hormones (e.g., insulin) bind to membrane-bound receptors like GPCRs or RTKs. 2. Paracrine Signaling: ○ In paracrine signaling, cells secrete signaling molecules that affect nearby cells. An example of this is neurotransmitter signaling between neurons and muscle cells. 3. Autocrine Signaling: ○ In autocrine signaling, cells respond to signals they secrete themselves. For instance, growth factors can act in an autocrine manner to regulate cell growth and division. Conclusion Cell signaling and signal transduction are vital processes that ensure cells respond appropriately to their environment. The interaction between ligands and receptors, such as GPCRs, leads to a series of intracellular events involving second messengers like cAMP, kinases, and transcription factors. These pathways allow cells to adjust their functions, whether it's regulating gene expression, metabolism, or responding to external stimuli. Angiogenesis and Cancer Growth Increased Blood Vessels in Tumors: Observing an increased number of stained blood vessels (brown) in ductal carcinoma suggests that angiogenesis (formation of new blood vessels) is active, likely to supply the tumor with oxygen and nutrients. VEGF and VEGFR: VEGF (vascular endothelial growth factor) stimulates mitosis and promotes angiogenesis by activating its receptor VEGFR. Tumors often overexpress VEGF and VEGFR, enhancing their blood supply. Laboratory Techniques Western Blot for VEGF and VEGFR: In a Western blot, VEGF and VEGFR can be detected using specific antibodies. VEGFR will appear at a higher molecular weight than VEGF. Beta-actin is used as a loading control to ensure equal amounts of protein in each sample. Angiogenic Activity in Tumors: An increase in VEGF levels in patient samples indicates active angiogenesis, contributing to tumor progression in solid tumors. VEGF Signaling and Its Role Signaling Molecule Properties: VEGF, a ligand for cell-surface receptors, is hydrophilic, preventing it from entering the cell. Instead, it binds to receptors on the cell surface, triggering intracellular signaling pathways. Second Messengers: Inside the cell, second messengers relay signals from surface receptors to other targets, such as in VEGF signaling. Phosphorylation: VEGFR is activated by phosphorylation at tyrosine residues following receptor dimerization, which is a key event in signal transduction. Inhibition of VEGF Signaling Drug Testing: Angomab, an inhibitor of VEGFR signaling, has the strongest effect by preventing VEGF from binding to its receptor and blocking receptor dimerization. Testing in a mouse model is essential for assessing the drug's effect on tumor growth, angiogenesis, and potential side effects. INTRODUCTION TO ENDOCRINE SYSTEM The endocrine system is a network of glands and organs that produce, store, and secrete hormones, which are chemical messengers that regulate various functions in the body. These hormones control vital processes such as growth, metabolism, reproduction, mood, and homeostasis (the maintenance of a stable internal environment). Unlike the nervous system, which uses electrical signals to communicate quickly between body parts, the endocrine system relies on the slow, longer-lasting release of hormones into the bloodstream to deliver messages to target cells or organs. Key Components of the Endocrine System: 1. Glands: Specialized organs that produce and secrete hormones. The major glands include: ○ Pituitary gland: Known as the "master gland," it controls other endocrine glands and regulates growth, blood pressure, and other important functions. ○ Thyroid gland: Regulates metabolism, energy production, and growth through the release of thyroid hormones. ○ Adrenal glands: Located on top of the kidneys, they release hormones such as cortisol and adrenaline, which help the body respond to stress. ○ Pancreas: Produces insulin and glucagon, which regulate blood sugar levels. ○ Gonads (ovaries and testes): Produce sex hormones (estrogen, progesterone, and testosterone) that control reproductive functions and secondary sexual characteristics. 2. Hormones: Chemical messengers produced by endocrine glands that travel through the bloodstream to target tissues. Hormones can affect specific organs or cells, regulating a wide range of bodily functions. 3. Target Organs/Cells: Specific tissues or organs that respond to particular hormones. Hormones bind to receptors on the target cells to trigger a specific action, such as the breakdown of glucose or the regulation of body temperature. Functions of the Endocrine System: Growth and Development: Hormones such as growth hormone (GH) and thyroid hormones play a key role in physical growth, bone development, and sexual maturation. Metabolism Regulation: Hormones like insulin and thyroid hormones regulate how the body converts food into energy. Reproduction: Sex hormones control reproductive functions, including menstruation, pregnancy, and the production of sperm and eggs. Stress Response: The adrenal glands release cortisol and adrenaline, which help the body respond to stress by increasing heart rate, blood pressure, and energy levels. Homeostasis: The endocrine system maintains internal balance by regulating temperature, hydration, and glucose levels in the blood. Hormonal Feedback Mechanisms: The endocrine system uses feedback loops, primarily negative feedback loops, to maintain balance. For example, when hormone levels are too high or too low, feedback signals trigger adjustments to bring the levels back to normal.