03. Module 3.pdf

Slide 2: The Cell Membrane Is Semipermeable and Selective Permeable to small uncharged molecules that move by diffusion. Impermeable to most polar and charged molecules. Water moves through diffusion and through water channels (aquaporins). Membrane proteins may regulate the passage of ma...

Slide 2: The Cell Membrane Is Semipermeable and Selective Permeable to small uncharged molecules that move by diffusion. Impermeable to most polar and charged molecules. Water moves through diffusion and through water channels (aquaporins). Membrane proteins may regulate the passage of material that cannot freely cross the membrane. Preserves the normal cell composition and properties. Slide 3: Four Types of Movements Diffusion: Movement from high to low concentration (down a concentration gradient). Osmosis: Water movement across a membrane to an area of higher solute concentration. Facilitated diffusion: Molecule movement down the gradient with the aid of a channel or carrier protein, no energy is required. Active transport: Moves substances against the concentration gradient or faster than passive transport; energy is required. Slide 4: Tonicity and Osmosis Tonicity: The ability of an extracellular solution to make water move in or out of a cell by osmosis. Osmolarity: The total concentration of all solutes, osmoles/liter (L); osmolality is osmoles/kilogram. One osmole: The amount of a substance that dissociates in solution to form one mole of osmotically active particles (NB: 1 mol/L NaCl is 2 osmol/L). If two solutions are separated by a membrane permeable to water, but not to solutes, water moves to the solution of higher osmolarity. Hypotonic, isotonic, and hypertonic compare the osmolarity of a cell and extracellular fluid. Slide 5: Osmosis Glossary Osmotic pressure: Caused by an imbalance of molecules on both sides of the membrane; it is proportional to the number of solute atoms or molecules (not their size).  Osmoregulation: The maintenance of osmotic balance (concentration of electrolytes, non- electrolytes, and water) across membranes. Electrolyte: A solute that dissociates into ions in water; Nonelectrolyte: A solute that doesn’t dissociate into ions in water. If electrolyte ions could passively diffuse across membranes, it would be impossible to maintain specific ion concentrations in compartments; ions require special mechanisms to cross semi-permeable membranes (i.e., facilitated diffusion and active transport). Slide 6: Diffusion versus Facilitated Diffusion Facilitated diffusion is carried out by carrier (transporter) proteins and channels. Facilitated diffusion is slower, and at high solute concentrations, the transporter/channel reaches its maximum rate and becomes saturated. Transporters saturate when all their binding sites are occupied; in a channel, ions have to shed most of their associated water molecules to pass through the channel. Glucose moves into most cells by facilitated diffusion through a carrier protein (such as GLUT 1). NB: Glucose moves into intestinal epithelial cells against its concentration gradient via a different transport mechanism (not facilitated diffusion). Slide 7: Passive versus Active Transport For an uncharged solute, the difference in concentration on both sides of the membrane is its concentration gradient. For a charged solute, the concentration and electrical gradients are used to calculate the electrochemical gradient. Passive transport: Uncharged solute crosses the membrane “downhill” its concentration gradient; a charged solute follows its electrochemical gradient. Active transport: Against solute’s electrochemical/concentration gradient (“uphill”). Active transport is mediated by proteins that use chemical energy (e.g., ATP, primary transport) or the electrochemical gradient generated by active transport (secondary transport). Slide 8: Types of Active Transport by Coupling and Direction Uniporters: Transport solutes from one side to the other side of a membrane.  Symporters (coupled transport): Typically, transfer one solute dependent upon the transfer of a second solute; the transfer is in the same direction. Antiporters (coupled transport): Typically, transfer one solute dependent upon the transfer of a second solute; the transfer of the second solute is in the opposite direction. Slide 9: Types of Active Transport by Energy Source Coupled carriers: The uphill transport of one solute is coupled to the downhill transport of another solute (secondary active transport). ATP-driven pumps: Couple uphill transport to the hydrolysis of ATP (primary active transport). Light-driven pumps: Mainly in bacterial cells. Slide 10: Active Transport through Ion Gradients The coupled transport allows the use of energy stored in the electrochemical gradient of one solute to transport the other (secondary active transport). Na+ is a frequently co-transported ion with its electrochemical gradient providing energy for the transport of a second molecule; sodium ions are subsequently pumped out of the cell by an ATP-driven Na+/K+ pump. The transport of Na+ into the cell has both favorable chemical gradient and electrical gradient. Slide 11: The Plasma Membrane Na+-K+ Pump: a P-type Transport ATPase Maintains [K+] higher inside cells, [Na+] higher outside the cells. Hydrolyzes ATP and it autophosphorylates (a P-type transport ATPase). Drives the transport of nutrients into the cells, regulates cytosolic pH, and cell volume (osmotic balance). Slide 12: The Na+/K+ Pump and Osmotic Balance Na+-K+ pump regulates cell volume by controlling the solute concentration. The plasma membrane is weakly permeable to water; water moves slowly in/out of cells down its concentration gradient (osmosis); in a hypotonic solution, cells lyse; in a hypertonic solution, cells shrink.  Inside, cells contain negatively charged organic molecules and accompanying cations for balance; this effect is counteracted by an opposing osmotic gradient with a high concentration of inorganic ions (e.g., Na+ and Cl-) in the extracellular fluid. The Na+/K+ pump maintains osmotic balance by pumping Na+ out. Slide 13: Ca2+ and H+ Pumps: P-type Transport ATPases Low cytosolic [Ca2+] is maintained by a Ca2+ ATPase and a Na+-Ca2+ exchanger (antiporter) driven by the Na+ electrochemical gradient. Ca2+ ATPase functions in the sarcoplasmic reticulum membrane of skeletal muscle cells. - When an action potential depolarizes the membrane, Ca2+ is released from the sarcoplasmic reticulum into the cytosol. - This release occurs through ligand-gated Ca2+-release channels, stimulating muscle contraction. - Ca2+ is then removed back into the sarcoplasmic reticulum by the Ca2+ ATPase pump. Slide 14: F-type Proton Pump ATPases Slide 14: F-type Proton Pump ATPases In the inner membrane of mitochondria. The H+ gradients across the membrane drive the synthesis of ATP from ADP and phosphate. The H+ gradients are generated during the electron-transport steps of oxidative phosphorylation. The ATP synthases can work in either direction; when pumping H+ against its gradient, these pumps are referred to as V-type pumps. Slide 15: ABC Transporters (ATPases) Two ATP-binding cassettes dimerize upon ATP binding. Specific for substrates (peptides, small molecules); can pump hydrophobic drugs out of the cell (e.g., the multidrug resistance protein, MDR). Can catalyze the flipping of lipids in the lipid bilayer.  Immune surveillance: An ABC transporter in the ER membrane transports peptides from protein degradation to the cell surface, where the peptides are “scanned” by cytotoxic T lymphocytes. Cystic fibrosis is due to a mutation in an ABC transporter that regulates a Cl- channel in the plasma membrane of epithelial cells. Slide 16: Putting It Together Carrier proteins transfer solutes across the lipid bilayer by undergoing conformational changes. Some carrier proteins transport a single solute downhill, while others transport a solute against its electrochemical gradient, using energy from ATP hydrolysis, or from the downhill flow of another solute (e.g., Na+). The family of P-type transport ATPases includes the Na+-K+ pump. Each ATPase sequentially phosphorylates and dephosphorylates itself during the pumping cycle. The ABC transporters are clinically important.