Movement of Molecules across Cell Membranes.pptx

Physiology Lectures for PharmD students (Pakistan)

1. Dr. Salman Ul Islam Unit#1 BASIC CELL FUNCTIONS Topic : Movement of molecules across cell membranes Physiology-A

2. Cell membrane The cell membrane, also called the plasma membrane, is found in all cells and separates the interior of the cell from the outside environment. The cell membrane consists of a lipid bilayer that is semipermeable. The cell membrane regulates the transport of materials entering and exiting the cell. Figure Cell membranes act as selective barriers. The plasma membrane separates a cell from its surroundings, enabling the molecular composition of a cell to differ from that of its environment. (B) In addition to a plasma membrane, eukaryotic cells also have internal membranes that enclose individual organelles. All cell membranes prevent molecules on one side from freely mixing with those on the other, as indicated schematically by the colored dots.

3. Cell membrane

4. Cell membrane Figure A cell membrane consists of a lipid bilayer in which proteins are embedded. (A) An electron micrograph of a plasma membrane of a human red blood cell seen in cross section. In this image, the proteins that extend from either side of the bilayer form the two closely spaced dark lines indicated by the brackets; the thin, white layer between them is the lipid bilayer. (B) Schematic drawing showing a three-dimensional view of a cell membrane. (A, by permission of E.L. Bearer.)

5. Figure 1 Cell membranes contain specialized membrane transport proteins that facilitate the passage of selected small, water-soluble molecules. Cell membranes, by contrast, contain membrane transport proteins (light green), each of which transfers a particular substance across the membrane. This selective transport can facilitate the passive diffusion of specific molecules or ions across the membrane (blue circles), as well as the active pumping of specific substances either out of (purple triangles) or into (green bars) the cell. For other molecules, the membrane is impermeable (red squares). The combined action of different membrane transport proteins allows a specific set of solutes to build up inside a membrane-enclosed compartment, such as the cytosol or an organelle.

6. Cell membrane Figure Cell membranes are packed with phospholipids. A typical membrane phospholipid molecule has a hydrophilic head and two hydrophobic tails.

7. Figure Phosphatidylcholine is the most common phospholipid in cell membranes. It is represented schematically in (A), as a chemical formula in (B), as a space-filling model in (C), and as a symbol in (D). This particular phospholipid is built from five parts: the hydrophilic head, which consists of choline linked to a phosphate group; two hydrocarbon chains, which form the hydrophobic tails; and a molecule of glycerol, which links the head to the tails. Each of the hydrophobic tails is a fatty acid—a hydrocarbon chain with a carboxyl (–COOH) group at one end; glycerol attaches via this carboxyl group, as shown in (B). A kink in one of the hydrocarbon chains occurs where there is a double bond between two carbon atoms. (The “phosphatidyl” part of the name of a phospholipid refers to the phosphate–glycerol–fatty acid portion of the molecule.)

8. Figure A hydrophilic molecule attracts water molecules. Both acetone and water are polar molecules: thus, acetone readily dissolves in water. Polar atoms are shown in red and blue, with δ– indicating a partial negative charge, and δ+ indicating a partial positive charge. Hydrogen bonds (red ) and an electrostatic attraction (yellow) form between acetone and the surrounding water molecules. Nonpolar groups are shown in gray.

9. Figure A hydrophobic molecule tends to avoid water. Because the 2-methylpropane molecule is entirely hydrophobic, it cannot form favorable interactions with water. This causes the adjacent water molecules to reorganize into a cagelike structure around it, to maximize their hydrogen bonds with each other.

10. Figure Amphipathic phospholipids form a bilayer in water. (A) Schematic drawing of a phospholipid bilayer in water. (B) Computer simulation showing the phospholipid molecules (red heads and orange tails) and the surrounding water molecules (blue) in a cross section of a lipid bilayer. (B, adapted from R.M. Venable et al., Science 262:223–228, 1993.) 

11. Transport through cell membrane All the cells in the body must be supplied with essential substances like nutrients, water, and electrolytes. Cells also must get rid of many unwanted substances like waste materials, and carbon dioxide. The cells achieve these by means of transport mechanisms across the cell membrane. Structure of the cell membrane is well suited for the transport of substances in and out of the cell. Lipids and proteins of cell membrane play an important role in the transport of various substances between extracellular fluid (ECF) and intracellular fluid (ICF).

12. Figure The rate at which a solute crosses a protein-free, artificial lipid bilayer by simple diffusion depends on its size and solubility. Many of the organic molecules that a cell uses as nutrients (red ) are too large and polar to pass efficiently through an artificial lipid bilayer that does not contain the appropriate membrane transport proteins.

13. Figure A transmembrane hydrophilic pore can be formed by multiple amphipathic α helices. In this example, five amphipathic transmembrane α helices form a water-filled channel across the lipid bilayer. The hydrophobic amino acid side chains on one side of each helix (green) come in contact with the hydrophobic lipid tails of the lipid bilayer, while the hydrophilic side chains on the opposite side of the helices (red ) form a water-filled pore.

14. Figure Water molecules diffuse rapidly through aquaporin channels in the plasma membrane of some cells. (A) Shaped like an hourglass, each aquaporin channel forms a pore across the bilayer, allowing the selective passage of water molecules. Shown here is an aquaporin tetramer, the biologically active form of the protein. (B) In this snapshot, taken from a real-time, molecular dynamics simulation, four columns of water molecules (blue) can be seen passing through the pores of an aquaporin tetramer (not shown). The space where the membrane would be located is indicated. (B, adapted from B. de Groot and H. Grubmüller , Science 294:2353–2357, 2001.)

15. Basic mechanism of transport Two types of basic mechanisms are involved in the transport of substances across the cell membrane: 1. Passive transport mechanism 2. Active transport mechanism

16. Basic mechanism of transport 1. Passive transport mechanism Passive mechanisms like diffusion use no energy.

17. Basic mechanism of transport Types of passive transport A. Simple diffusion B. Facilitated diffusion A. Simple diffusion Diffusion is the movement of particles down their gradient. A gradient is any imbalance in concentration and moving down a gradient just means that the particle is trying to be evenly distributed everywhere, like dropping food coloring in water. We call this evening-out moving “downhill”, and it doesn’t require energy. The molecule most likely to be involved in simple diffusion is water - it can easily pass through cell membranes. When water undergoes simple diffusion, it is known as osmosis.

18. Basic mechanism of transport

19. Basic mechanism of transport A. Simple diffusion Simple diffusion is pretty much exactly what it sounds like – molecules move down their gradients through the membrane. Molecules that practice simple diffusion must be small and nonpolar*, in order to pass through the membrane. Simple diffusion can be disrupted if the diffusion distance is increased. If the alveoli in our lungs fill with fluid (pulmonary edema), the distance the gases must travel increases, and their transport decreases.

20. Figure Solutes cross cell membranes by either passive or active transport. Some small, nonpolar molecules such as CO 2 can move passively down their concentration gradient across the lipid bilayer by simple diffusion, without the help of a membrane transport protein. Most solutes, however, require the assistance of a channel or transporter. Passive transport, which allows solutes to move down their concentration gradients, occurs spontaneously; active transport against a concentration gradient requires an input of energy. Only transporters can carry out active transport, and the transporters that perform this function are called pumps.

21. Basic mechanism of transport B. Facilitated diffusion Facilitated diffusion is diffusion that is helped along (facilitated by) a membrane transport channel. These channels are glycoproteins (proteins with carbohydrates attached) that allow molecules to pass through the membrane. These channels are almost always specific for either a certain molecule or a certain type of molecule (i.e., an ion channel), and so they are tightly linked to certain physiologic functions.

22. Figure Inorganic ions and small, polar organic molecules can cross a cell membrane through either a transporter or a channel. A channel forms a pore across the bilayer through which specific inorganic ions or, in some cases, polar organic molecules can diffuse. Ion channels can exist in either an open or a closed conformation, and they transport only in the open conformation, as shown here. Channel opening and closing is usually controlled by an external stimulus or by conditions within the cell.

23. Figure Inorganic ions and small, polar organic molecules can cross a cell membrane through either a transporter or a channel. A transporter undergoes a series of conformational changes to transfer small solutes across the lipid bilayer. Transporters are very selective for the solutes that they bind, and they transfer them at a much slower rate than do channels.

24. Basic mechanism of transport B. Facilitated diffusion Glucose and amino acids are transported by facilitated diffusion. Glucose or amino acid molecules cannot diffuse through the channels because the diameter of these molecules is larger than the diameter of the channels. Molecule of these substances binds with carrier protein. Now, some conformational change occurs in the carrier protein. Due to this change, the molecule reaches the other side of the cell membrane

25. Basic mechanism of transport 2. Active transport mechanism Sometimes the body needs to move molecules against their gradient. This is known as moving “uphill” and requires energy from the cell. Active transport requires energy, which is obtained mainly by breakdown of high energy compounds like adenosine triphosphate (ATP).

26. Figure The Na+ pump uses the energy of ATP hydrolysis to pump Na+ out of animal cells and K+ in. In this way, the pump helps keep the cytosolic concentrations of Na+ low and K+ high.

27. SGLT2= Sodium-glucose transport protein 2

28. The sodium-potassium pump is an example of an antiporter as sodium and potassium are pumped in opposite directions. This is primary active transport as both molecules are pumped against their gradient and require ATP hydrolysis. Glucose uptake in the kidneys is an example of symport as its movement is coupled to the parallel transport of sodium. This is secondary active transport as the sodium is moving passively down an electrochemical gradient.