Comprehensive Study Notes PDF

Comprehensive Study Notes Module 4 SGLT Inhibitor: Used to treat type 2 diabetes. GLUT2: Low affinity (usually), active (usually out of cell). GLUT2: Facilitates glucose release into the blood or brings it inside the cell. Module 5 Resting Potential: Refers only to excitable cells. Effectively i...

Comprehensive Study Notes Module 4 SGLT Inhibitor: Used to treat type 2 diabetes. GLUT2: Low affinity (usually), active (usually out of cell). GLUT2: Facilitates glucose release into the blood or brings it inside the cell. Module 5 Resting Potential: Refers only to excitable cells. Effectively impermeable due to potassium (K+) leaking out, causing sodium (Na+) channels to remain closed. Saltatory Conduction: Depolarization jumps from one node of Ranvier to the next along a myelinated axon. Ca2+ ATPase: Pumps calcium ions back into the sarcoplasmic reticulum. Transmitter-gated channels convert chemical signals into electrical signals. Neurotransmitters facilitate ion channels, and the voltage sensitivity of these channels affects membrane potential. Module 7 A-type Lamin: Encoded by LMNA gene. Two types of nuclear lamin: A and B. EDMD (Emery-Dreifuss Muscular Dystrophy): Affects skeletal and cardiac muscles, leading to bradycardia and heart failure. Hutchinson-Gilford Progeria Syndrome (HGPS): Affects pediatric patients and is associated with early aging. Module 8: Actin Polymerization Nucleation: Slow formation of actin filaments, leading to a steady state where both ends grow at the same rate. Hydrolysis: Conversion of ATP-bound actin (T-form) to ADP-bound actin (D-form), promoting depolymerization. Actin-Related Protein (ARP): Catalyzes polymerization at the minus end to allow elongation at the plus end. Critical Concentration (Cc): If actin concentration is lower than Cc, no growth occurs. If higher than Cc, growth occurs. Steady State: Both ends of the actin filament remain balanced. Dissociation Constant (Kd): High Kd corresponds to high free energy, which destabilizes the filament. Module 8: Accessory Proteins & Microtubules Accessory Proteins: Link filaments to other cellular components. Tubulin Dynamics: Alpha-tubulin does not break down (- end), but beta-tubulin undergoes hydrolysis (+ end). Dynamic Instability: Microtubules grow and shrink rapidly. Treadmilling: Actin filaments add subunits at one end while removing from the other. Catastrophe: Rapid shrinkage of microtubules, followed by rescue when growth resumes. F-Actin: Filamentous actin that arranges from head to toe. G-Actin: Globular actin subunits. Module 9 Profilin: Moves actin from the thymosin pool to the plus end, promoting filament growth. Cofilin: Disassembles old actin filaments (ADP-bound) to allow new actin to form. Stathmin: Reduces the rate of elongation. Gelsolin: Facilitates actin filament dynamics by binding to the plus end and promoting depolymerization. Intermediate Filaments: Non-polar structures that provide structural support to cells. Vimentin-Like Proteins: Provide support to muscle cells by stabilizing intermediate filaments. Microtubule-Severing Proteins: Disassemble microtubules and promote the formation of new ones. Tropomodulin: Caps the minus end of actin filaments, preventing disassembly and stabilizing the filament. Module 10: Motor Proteins Kinesin: Responsible for anterograde transport (toward the plus end) and is ATP- dependent. Dynein: Responsible for retrograde transport (toward the minus end) and is the largest and fastest motor protein. Troponin: Binds to calcium (Ca2+), allowing myosin to bind to actin by moving tropomyosin out of the way. Power Stroke: Occurs when myosin releases ADP and phosphate, causing muscle contraction. Myosin: Has speed but lacks processivity, unlike kinesin and dynein which are processive. Rigor State: Myosin is tightly bound to actin without any attached nucleotide, causing a locked conformation. Skeletal Muscle Fibers: Composed of large cells formed by the fusion of multiple precursor cells. ATP Hydrolysis: Causes the myosin head to enter a cocked conformation, ready for the next movement. Action Potential: Prompts the opening of T-tubules, essential for nerve and muscle cell activation. Module 10 (Continued) KRPs (Kinesin-Related Proteins): Dependent on ATP for movement. The release of ATP causes movement. M Line: Attaches to Myosin II. Kinesin Tail: Determines the cargo being transported. Module 11: Dynein and Cell Movement Dynein: Bending action in flagella and cilia, responsible for retrograde transport. Axoneme: Structure involved in flagella/cilia movement, dynein "bridges" facilitate sliding. Basal Bodies: Found on the cell surface, anchor cilia and flagella. Cell Movement Structures Lamellipodia (2D Movement): Involved in cell movement. Lamellum is the more stable region behind the lamellipodia. Filopodia (1D Sensing): Involved in cell migration, neural outgrowth, and wound healing. Kinesin and Dynein Kinesin: Transports cargo toward the axon (anterograde). Dynein: Transports cargo toward the cell body (retrograde). Microtubule Dynamics Dynamic Instability: Rapid growth and shrinkage of microtubules. Platelet Activation: Involves severing, uncapping, elongation, recapping, and cross-linking of filaments. Gelsolin: Necessary for actin filament severing, activated by PIP2 and Ca2+. Microtubule and Actin Behavior Microtubules: Show dynamic instability (growth and shrinkage). Actin Filaments: Exhibit treadmilling (disassembly at one end, assembly at the other). Minus and Plus Ends Minus Side: Directed toward the centrosome, delivering cargo to the center. Plus Side: Directed toward the cell periphery, involved in growth. Troponin (Muscle Contraction) Troponin binds to calcium, facilitating muscle contraction. Module 10: Kinesin, Dynein, and Muscle Contraction Kinesin: Responsible for anterograde movement, ATP-dependent. Dynein: Responsible for retrograde movement, the largest and fastest motor protein. Troponin: Binds to Ca2+, allowing myosin to bind to actin by moving tropomyosin. Power Stroke: Myosin releases ADP and phosphate, causing muscle contraction. Myosin: Lacks processivity but has high speed. Kinesin and Dynein, on the other hand, are processive. Rigor State: Myosin binds firmly to actin in the absence of a nucleotide. Opposing Head Movement: Sliding of myosin through muscle filaments. Contraction of Skeletal Fibers: Large muscle fibers result from the fusion of multiple precursor cells. Sarcomere: Comprised of plus ends with Z-filaments. ATP Hydrolysis: Causes the myosin head to enter a cocked conformation, essential for movement. Action Potential: Prompts the opening of T-tubules, necessary for nerve and muscle cell function. Module 9: Actin Dynamics and Microtubules Profilin: Moves actin from the thymosin pool to the plus end, facilitating polymerization. Cofilin: Dissolves old actin filaments to make new ones using ADP. Stathmin: Reduces the rate of elongation by binding to tubulin dimers. Gelsolin: Regulates actin dynamics, binding to the plus end to promote severing. Capping Proteins CAP2 (Tubulin): Stabilizes the plus end of microtubules. MAP (Microtubule-Associated Proteins): Stabilize microtubules and prevent disassembly, aiding in microtubule formation. ARP Complex (Actin-Related Proteins) Nucleates actin filament growth. Intermediate Filaments Vimentin-Like Proteins: Provide muscle cell support through intermediate filaments, which lack polarity. Microtubule-Severing Proteins Sever microtubules to create new microtubules and facilitate turnover. Tropomodulin Caps the minus end of actin filaments, preventing disassembly and stabilizing the structure. Module 8: Accessory Proteins and Microtubule Dynamics Accessory Proteins: Link filaments to other cell components, providing structural support. GTP (Tubulin): Tubulin α-subunits are never broken down, while β-subunits break down via hydrolysis. Actin Treadmilling: Actin grows at one end and disassembles at the other, maintaining a steady size. Dynamic Instability: Refers to microtubules’ ability to rapidly grow and shrink. Steady State: Equilibrium where the loss and addition of subunits are balanced. Catastrophe: Refers to the shrinkage of microtubules, while Rescue refers to their regrowth. Nucleotide States of Actin and Tubulin T-Form: Bound to ATP (actin) or GTP (tubulin). D-Form: Bound to ADP (actin) or GDP (tubulin). Microtubules Involved in intracellular transport and segregating chromosomes during cell division. Intermediate Filaments Fibrous, provide structural support for cells. Actin/Myosin Globular proteins that work together in muscle contraction. Microtubule Nucleation Occurs at the γ-tubulin ring complex, which serves as a nucleation site for microtubules. Branching Nucleation Branching occurs from pre-existing cells to make new actin filaments. Module 4: GLUT Transporters and SALT Inhibitors SGLT Inhibitors: Used to treat type 2 diabetes by reducing glucose reabsorption. GLUT2: Lower affinity glucose transporter that releases glucose into the blood. GLUT2: Typically active when glucose is moved out of the cell. Module 5: Resting Potential and Voltage Gated Channels Resting Potential: Refers only to excitable cells where membrane potential remains stable. Effectively Impermeable: Due to potassium leakage channels. Saltatory Conduction: Depolarization travels along a myelinated axon by jumping between nodes. Voltage-Sensitive Channels Ca2+ ATPase: Pumps calcium ions back into storage to restore resting potential. Neurotransmitter-Gated Channels: Facilitate ion flow to alter membrane potential. Module 7: Nuclear Lamin A and Laminopathies A-type Lamin: Encoded by the LMNA gene and has three forms (A, B, C). Associated Conditions: Skeletal and cardiac defects like bradycardia and heart failure. Hutchinson-Gilford Progeria Syndrome (HGPS): A condition affecting pediatric patients, characterized by accelerated aging.