14B Facilitated Diffusion across Membranes

Ion Binding and Function: Valinomycin facilitates the transportation of potassium ions (K+) without requiring energy costs for binding.
Hydration Shell Replacement: The peptide carbonyl groups of valinomycin replace the water hydration shell around K+, thereby enhancing the permeability of K+ across biological membranes.
Selectivity: Valinomycin exhibits a preference of 30,000-fold for K+ compared to sodium ions (Na+).
Concentration Dependence: The direction of ion flow is dependent on the concentration difference across the membrane, illustrating the concept of selective permeability.

Ion Conduction: The K+ channel permits potassium ions to flow down their electrochemical gradient.
Ionic Selectivity: It is selective for K+ over Na+ due to the similarities in their ionic radii and charges.
Gated Channels: The channels have gating mechanisms that result in opening and closing behaviors, critical for transmitting electrical impulses in neurons.

Selective Filter: The potassium ion channel has a distinct size-selective filter, identified with the PDB ID 1K4C.
Tetrameric Structure: The K+ channel is characterized as a tetramer with a pore lined with backbone carbonyls that perfectly solvate K+ ions.

Conformational States: The flow of ions must be tightly controlled, requiring channels to exist in either open or closed conformations.
Activation Mechanisms:
- Channels can be opened by binding to specific ligands.
- Some can be activated by changes in voltage across the membrane, exemplified by action potentials which result in transient changes in ion concentrations.

Function: Aquaporins facilitate the rapid movement of water across cell membranes.
Tetrameric Structure: Comprising four pores sized at 2.8 Å, aquaporins are engineered for the selective transport of water.
Ion Exclusion Mechanism: They exclude ions, such as H+, primarily through mechanisms of electrostatic repulsion and the requirement for water to move in single file, impeding the formation of hydrogen bond networks between water molecules.
Osmotic Pressure Regulation: Aquaporins equalize osmotic pressure without disrupting the gradients of ions and H+.

Characteristics of Facilitated Diffusion:
- Greatly increases permeability across membranes.
- Highly selective transport mechanism.
- Relies on a limited number of specialized proteins.
- Driven by the concentration differences of solutes.
- Exhibits saturation kinetics whereby maximal transport is reached when the number of available transporters is fully utilized.
Flux Dynamics: The rates of transport vary depending on the concentration difference across the membrane.
- Non-mediated Transport: Demonstrates a maximum rate when all transporters are engaged.

Structural Composition: Glut1 has 12 membrane-spanning helices, whereas it switches between two conformations (never existing as an open pore).
Passive Transport Mechanism: Facilitated diffusion through Glut1 is driven by the concentration gradient of D-glucose across the plasma membrane of erythrocytes, and this process is reversible.
Substrate Specificity: Glut1 is specifically designed for D-glucose transport, allowing for high diffusion rates characterized by saturation behavior at varying glucose concentrations.

Overview: Glut permeases are a major family of glucose transport proteins, comprising 14 members grouped into 4 classes.
Class I Members:
- Glut1: Found in erythrocytes.
- Glut2: Located in the liver, primarily transports glucose out for usage by other tissues.
- Glut3: Present in neurons, noted for its high affinity for D-glucose.
- Glut4: Found in adipose and muscle tissues, stored in intracellular vesicles and exposed to the cell surface in response to insulin.
Metabolic Functionality: Glut4 serves to regulate glucose uptake in response to insulin signaling, while Glut1 is effective in red blood cells due to their minimal energy requirements and the fixed concentration of transporters.