Membrane Transport II Active and vesicular transport across membranes Cell Biology for Clinical Pharmacy Students MD102 Module II: Cell Functions (Lecture # 7) Membrane Transport II Active and vesicular transport across membranes Dr. Ahmed Sherif Attia ahmed.attia.e.learning@gmail.com https://sites.google.com/site/ahmedsattia/

Objectives By the end of this lecture you should be familiar with: Active transport (primary and secondary) Vesicular transport

Active Transport Some transport proteins (carrier proteins) can move substances through the membrane against the concentration gradient. Active transport typically requires two carrier protein active sites: one to recognize the substance to be carried, and one to release ATP to provide the energy for the protein carriers or "pumps".

Active Transport cont. In other cases, concentration gradients of ions, typically H+ or Na+ ions, can be used to provide the energy needed to move something through a membrane. For example, the substance to be moved is "coupled" to the concentration of H+, and while to H+ is moving "down" through the carrier channel, the substance is transported "up".

Sodium-Potassium Exchange Pump

Sodium-Potassium Exchange Pump The pump, with bound ATP, binds 3 intracellular Na+ ions. ATP is hydrolyzed, leading to phosphorylation of the pump and subsequent release of ADP. A conformational change in the pump exposes the Na+ ions to the outside. The phosphorylated form of the pump has a low affinity for Na+ ions, so they are released.

Sodium-Potassium Exchange Pump The pump binds 2 extracellular K+ ions. This causes the dephosphorylation of the pump, reverting it to its previous conformational state, transporting the K+ ions into the cell. The unphosphorylated form of the pump has a higher affinity for Na+ ions than K+ ions, so the two bound K+ ions are released. ATP binds, and the process starts again.

Indirect (secondary) active transport Uses proteins similar to those for facilitated diffusion. Couples the movement of several different molecules in each cycle. Saturates when substance reaches high concentrations due to lack of available protein.

Indirect (secondary) active transport The gradient for one molecule can cause the other to move against its own diffusion gradient. Normal active transport (Na-K ATPase) makes a strong Na gradient, which in turn powers many secondary active transport mechanisms. Example:  Na-Glucose cotransport.

ATP is not directly involved, but it sets up the electrochemical gradient used to propel the driver.

Vesicular Transport Also called bulk transport Transport of large particles and macromolecules across plasma membranes. Directional Descriptive Terms Exocytosis: moves substance from the cell interior to the extracellular space. Endocytosis: enables large particles and macromolecules to enter the cell.

In phagocytosis, a cell engulfs a particle by wrapping pseudopodia around it and packaging it within a membrane-enclosed sac large enough to be classified as a vacuole. The particle is digested after the vacuole fuses with a lysosome containing hydrolytic enzymes.

In pinocytosis, the cell “gulps” droplets of extracellular fluid into tiny vesicles. It is not the fluid itself that is needed by the cell, but the molecules dissolved in the droplet. Because any and all included solutes are taken into the cell, pinocytosis is nonspecific in the substances it transports.

Receptor-mediated endocytosis enables the cell to acquire bulk quantities of specific substances, even though those substances may not be very concentrated in the extracellular fluid. Embedded in the membrane are proteins with specific receptor sites exposed to the extracellular fluid. The receptor proteins are usually already clustered in regions of the membrane called coated pits, which are lined on their cytoplasmic side by a fuzzy layer of coat proteins.

Extracellular substances (ligands) bind to these receptors. When binding occurs, the coated pit forms a vesicle containing the ligand molecules. After this ingested material is liberated from the vesicle, the receptors are recycled to the plasma membrane by the same vesicle.

In exocytosis, the transport vesicle fuses with the plasma membrane, making the inside of the vesicle continuous with the outside of the cell. Exocytosis is used in secretion of protein hormones (insulin), serum proteins, extracellular matrix (collagen).

Comparison between different types of membrane transport Mechanism Process Factors affecting the rate Substance involved (site) Diffusion Molecular movement of solutes: direction is determined by the relative concentration Size of gradient, size of molecule, charge, lipid solubility, temperature Small inorganic ions, lipid soluble materials (all cells) Osmosis Movement of water molecules towards solutions of relatively higher solute concentrations; requires a selectively permeable membrane Concentration gradient, opposing osmotic or hydrostatic pressure, number of aquaporins Water only

Carrier mediated Mechanism Process Factors affecting the rate Substance involved (site) Carrier mediated Facilitated diffusion Carrier proteins passively transport solutes across membrane down a concentration gradient Size of gradient, temperature, availability of carrier Glucose and amino acids (all cells but different regulations) Active transport Carrier proteins actively transport solutes across membrane often against concentration gradient Availability of carrier, substrates and ATP Na+, K+, Ca2+, Mg 2+ (all cells). Other solutes by specialized cells. Secondary active transport Carrier proteins passively transport 2 solutes, with one moving down its concentration gradient. The cell must expend later ATP to expel the driver (specialized cells)

Vesicular transport Mechanism Process Factors affecting the rate Substance involved (site) Vesicular transport Endocytosis Creation of membranous vesicles containing solids or liquids ATP. The stimulus and the mechanics are incompletely understood Fluids and nutrients (all cells). Debris and pathogens (specialized cells. Exocytosis Fusion of the vesicles containing liquids or solid (or both) with the cell membrane) Fluids and debris (all cells).