Transport across cell membrane

transport of substances across cell membrane

1. Transport across the cell membrane Dr AnuPriya J 10/4/2017 msrmc 1

2. Transport of substances across the cell membrane is necessary to maintain the normal functioning of the cells in our body. 10/4/2017 msrmc 2 Introduction

3. Transport across the cell membrane Lipid soluble substances, water & urea can easily pass through the lipid bilayer of the cell membrane The lipid bilayer of the cell membrane is impermeable to lipid insoluble substances such as ions & charged or polar molecules like glucose These substances pass through specialized protein channels, carrier proteins & active pump mechanisms Large macromolecules are transported through vesicles. 10/4/2017 msrmc 3

4. Types Passive transport Diffusion – simple, facilitated Osmosis Active transport Primary Secondary Vesicular transport Endocytosis Exocytosis Transcytosis 10/4/2017 msrmc 4

5. NO ENERGY NEEDED : Diffusion Osmosis Facilitated Diffusion ENERGY NEEDED : Active Transport ANALOGY: 10/4/2017 msrmc 5

6. NO ENERGY NEEDED : Diffusion Osmosis Facilitated Diffusion ENERGY NEEDED : Active Transport ANALOGY: 10/4/2017 msrmc 6

7. Passive transport Diffusion- Simple Facilitated Osmosis 10/4/2017 msrmc 7

8. Diffusion-simple It is the movement of ions or molecules from a region of their high concentration to a region of their low concentration, without the expenditure of energy Movement is towards the concentration gradient until an equilibrium is achieved. 10/4/2017 msrmc 8

9. Diffusion HIGH to LOW concentration 10/4/2017 msrmc 9

10. Distilled water Potassium manganate (vii) crystals a) The crystals starts to dissolve, forming a region of high concentration of solute molecules. b) The molecules diffuse out along the concentration gradient in all direction. c) Eventually the molecules spread throughout the water uniformly. Purple solution A sample experiment to illustrate the physical process of diffusion 10/4/2017 msrmc 10

11. Factors affecting the rate of diffusion 10/4/2017 msrmc 11 Factor Effect on the rate of simple diffusion Diffusion gradient/ concentration difference The steeper, the higher the rate Size of molecules or ions/ Molecular weight The smaller the size, the higher the rate Indirectly proportional Temperature The higher the temperature, the higher the rate Diffusion medium Rate in gas > rate in liquid > rate in solid Surface area The larger the surface area, the higher the rate

12. Factors affecting the rate of diffusion 10/4/2017 msrmc 12 Factor Effect on the rate of simple diffusion Solubility Directly proportional Thickness of membrane Indirectly proportional FICK’S LAW OF DIFFUSION

13. Simple diffusion Diffusion through lipid matrix Lipophilic /hydrophobic/ nonpolar /uncharged substances such as O 2 ,CO 2 ,N 2 ,fatty acids, alcohol, steroid hormones, etc., Water as it is a small molecule with high kinetic energy Urea 10/4/2017 msrmc 13

14. Simple diffusion Ionic diffusion – through channel proteins Ions diffuse through the ion channels. They are either open or gated. Open/leak channels – ex: K+ channels Gated channels open when stimulus is given Voltage gated Ligand gated Mechano sensitive gated 10/4/2017 msrmc 14

15. Inhaled and exhaled air O 2 CO 2 Oxygenated blood Deoxygenated blood Red blood cell Capillary wall Alveolus wall Air sac GASEOUS EXHANGE BY SIMPLE DIFFUSION IN THE ALVEOLUS 10/4/2017 msrmc 15

16. Facilitated diffusion Facilitated diffusion is the movement of specific molecules (or ions) across the plasma membrane, assisted by a carrier protein. The direction of movement is down the c oncentration gradient of the molecules concerned. No energy required. 10/4/2017 msrmc 16

17. Facilitated diffusion 10/4/2017 msrmc 17

18. Difference between carrier proteins & channel proteins Carrier proteins bind to larger molecules, and change their shape so molecules can diffuse through. Channel proteins provide water filled pores for charged ions to pass through 10/4/2017 msrmc 18

19. Difference between simple and passive diffusion Simple diffusion Facililated diffusion Mechanism Concentration gradient Concentration gradient Through carrier molecule Rate of diffusion Increase with increase in concentration gradient Reaches plateau (saturation of carrier protein) Example Ions through ion channels GLUT for glucose 10/4/2017 msrmc 19

20. 0smosis Osmosis is the movement of water molecules (solvent) through a selectively permeable membrane/ semipermeable membrane like the cell membrane. Water diffuses across a membrane from an area of high concentration to an area of low concentration. 10/4/2017 msrmc 20

21. Osmosis Semi-permeable membrane is permeable to water, but not to the solute i.e.,sugar 10/4/2017 msrmc 21

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23. Tonicity Osmolality of a solution relative to plasma Sodium ion is the major contributor to tonicity of ECF 10/4/2017 msrmc 23

24. Hypertonic Solutions Contain a high concentration of solute relative to another solution (e.g. the cell's cytoplasm). When a cell is placed in a hypertonic solution, the water diffuses out of the cell, causing the cell to shrivel. 10/4/2017 msrmc 24

25. Hypotonic Solutions Contain a low concentration of solute relative to another solution (e.g. the cell's cytoplasm). When a cell is placed in a hypotonic solution, the water diffuses into the cell, causing the cell to swell and possibly explode. 10/4/2017 msrmc 25

26. Iso tonic Solutions Contain the same concentration of solute as another solution (e.g. the cell's cytoplasm). When a cell is placed in an isotonic solution, the water diffuses into and out of the cell at the same rate. The fluid that surrounds the body cells is isotonic. 10/4/2017 msrmc 26

27. Interactive Red Blood Cell Click 10/4/2017 msrmc 27

28. Hypertonic solution Isotonic solution Hypotonic solution Remains of cell surface membrane Crenation : Red blood cell shrinks and turns ’spiky’ Red blood cell Swells up Haemolysis : Red blood cell finally burst CRENATION AND HAEMOLYSIS OF RED BLOOD CELL 10/4/2017 msrmc 28

29. Isotonic solution – 0.9% NaCl , 5% dextrose in water Hypotonic solution – treat dehydration Hypertonic solution – mannitol – treat cerebral edema 10/4/2017 msrmc 29

30. Filtrn – oncotic press – mvt rltn bw tissue fluid n blood vessel ,,,,, tonicity & osmotic press mvt rltd btw cell and surrounding fluid Osmotic press dep on no of mol rather than type of mol ... Diff from oncotic press 10/4/2017 msrmc 30

31. Osmotic pressure Movement of water/solvent molecules to a region of greater solute concentration can be prevented by applying pressure to the more concentrated solution. This pressure necessary to prevent the movement of solvent molecules into the solution is known as osmotic pressure Normal osmotic pressure of ICF= Osm P of ECF As osm p on both sides of cell memb constant – cell vol kept constant 10/4/2017 msrmc 31

32. Note Osmolality & osmolarity are not determined by the mass of the substance, but is determined by the number of osmoles / osmotically active particles Osmolarity – no of Osm /L of solution Osmolality – no of Osm /kg of solvent expressed as no of Osm /L of water 10/4/2017 msrmc 32

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34. Active transport Primary secondary 10/4/2017 msrmc 34

35. Active Transport Molecules move against the concentration gradient (low to high) Energy must be provided Exhibit saturation kinetics 10/4/2017 35 Dr.Anu Priya J

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37. Active transport is divided into two types according to the source of the energy used to cause the transport: 1. Primary active transport 2. Secondary active transport. Active Transport 10/4/2017 37 Dr.Anu Priya J

38. Primary active transport They use the energy directly from the hydrolysis of ATP. Sodium potassium Pump Calcium pump Hydrogen Potassium pump 10/4/2017 38 Dr.Anu Priya J

39. Sodium potassium pump 10/4/2017 39 Dr.Anu Priya J

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41. Sodium potassium pump - present in all eukaryotic cells Functions: Maintains sodium potassium concentration difference across the cell membrane. Maintains volume of the cell. Causes negative electrical charge inside the cell – electrogenic pump Essential for oxygen utilization by the kidneys 10/4/2017 Dr.Anu Priya J 41

42. Calcium pump 10/4/2017 42 Dr.Anu Priya J

43. Secondary active transport Energy utilised in the transport of one substance helps in the movement of the other substance. Energy is derived secondarily, from energy that has been stored in the form of ionic concentration differences of secondary molecular or ionic substances between the two sides of a cell membrane, created originally by primary active transport . 10/4/2017 43 Dr.Anu Priya J

44. Co-transport- symport The transport of Na+ via its concentration gradient is coupled to the transport of other substances in the same direction Carrier protein E.g SGLT Sodium glucose Co-transport 10/4/2017 44 Dr.Anu Priya J

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47. Counter transport The transport of Na+ via its concentration gradient is coupled to the transport of other substance in the opposite direction Sodium-Hydrogen counter transport in the proximal tubule of the kidneys Sodium-Calcium exchanger in the cardiac cells 10/4/2017 47 Dr.Anu Priya J

48. Counter transport 10/4/2017 48 Dr.Anu Priya J

49. Cardiac glycosides -Digitalis & Ouabain – management of heart failure Inhibits Na + -K + pump Accumulation of Na + inside the cell & prevention of K + influx Intracellular accumulation of Na + , decreases Na + gradient from outside to inside. Applied aspects 10/4/2017 49 Dr.Anu Priya J

50. Calcium efflux through sodium-calcium exchanger in the membrane utilizes sodium gradient. Decreased sodium gradient decreases calcium efflux causing increase in cytosolic calcium concentration, that promotes myocardial contractility. Applied aspects 10/4/2017 50 Dr.Anu Priya J

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52. Applied aspects Activation of Na + -K + pump: Thyroxine , Insulin, Aldosterone Inhibition of Na + -K + pump: Dopamine, Digitalis, Hypoxia, Hypothermia 10/4/2017 52 Dr.Anu Priya J

53. Difference between Facilitated diffusion and Active transport In both instances, transport depends on carrier proteins that penetrate through the cell membrane, as is true for facilitated diffusion. However, in active transport, the carrier protein functions differently from the carrier in facilitated diffusion because it is capable of imparting energy to the transported substance to move it against the electrochemical gradient. 10/4/2017 53 Dr.Anu Priya J

54. Vesicular transport 10/4/2017 msrmc 54

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56. Vesicular transport Endocytosis Exocytosis Transcytosis 10/4/2017 msrmc 56

57. Endocytosis/Exocytosis For substances the cell needs to take in ( endo = in) or expel ( exo = out), that are too large for passive or active transport 10/4/2017 msrmc 57

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59. Endocytosis The material makes contact with the cell membrane Cell membrane then invaginates Invagination is then pinched off leaving the cell membrane intact 10/4/2017 msrmc 59

60. Types of Endocytosis receptor mediated endocytosis phagocytosis (solids) pinocytosis (liquids) 10/4/2017 msrmc 60

61. 10/4/2017 msrmc 61 Types of Endocytosis

62. Ex: White Blood Cells surround and engulf bacteria by P hagocytosis . Pinocytosis – amino acids, fatty acids Receptor mediated endocytosis – LDL, Nerve growth factor, vitamins, hormones, HIV virus entering the T cell etc., 10/4/2017 msrmc 62

63. Exocytosis The process of release of macromolecules from the cells to the exterior . Vesicles containing material to be exposed, bind to the cell membrane Area of fusion breaks down leaving the contents of the vesicle outside & the cell membrane intact Reverse pinocytosis or emeiocytosis Requires calcium & energy Secretory granules , hormones 10/4/2017 msrmc 63

64. 10/4/2017 msrmc 64 Exocytosis

65. 10/4/2017 msrmc 65 Exocytosis

66. Vesicles endocytosed on one side of the cell; exocytosed on the opposite side. Caveolin mediated (Rafts & Caveolae ) Also known as cytopempsis Transport of substances across the endothelial cells of blood vessels to interstitial fluid 10/4/2017 msrmc 66 Transcytosis

67. Transcytosis 10/4/2017 msrmc 67

68. Thank you 10/4/2017 msrmc 68

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70. 10/4/2017 Dr.Anu Priya J 70 Hydrogen Potassium pump H + -K + ATPase

71. Hydrogen Potassium pump H + -K + ATPase Gastric glands - parietal cells - hydrochloric acid secretion Renal tubules - intercalated cells in the late distal tubules and cortical collecting ducts. 10/4/2017 71 Dr.Anu Priya J

72. Present in lysosome and endoplasmic reticulum Pumps proton from cytosol into these organelles. Proton pump H + ATPase 10/4/2017 72 Dr.Anu Priya J

73. Calcium pump Calcium ions are normally maintained at extremely low concentration in the intracellular cytosol of virtually all cells in the body, at a concentration about 10,000 times less than that in the extracellular fluid. This is achieved mainly by two primary active transport calcium pumps. One is in the cell membrane and pumps calcium to the outside of the cell. The other pumps calcium ions into one or more of the intracellular vesicular organelles of the cell, such as the sarcoplasmic reticulum of muscle cells and the mitochondria in all cells. 10/4/2017 73 Dr.Anu Priya J

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75. In counter-transport, sodium ions again attempt to diffuse to the interior of the cell because of their large concentration gradient. However, this time, the substance to be transported is on the inside of the cell and must be transported to the outside. Therefore, the sodium ion binds to the carrier protein where it projects to the exterior surface of the membrane, while the substance to be countertransported binds to the interior projection of the carrier protein. Once both have bound, a conformational change occurs, and energy released by the sodium ion moving to the interior causes the other substance to move to the exterior. 10/4/2017 75 Dr.Anu Priya J

76. Different substances that are actively transported through at least some cell membranes include sodium ions, potassium ions, calcium ions, iron ions, hydrogen ions, chloride ions, iodide ions, urate ions, several different sugars, and most of the amino acids. 10/4/2017 76 Dr.Anu Priya J

77. At times, a large concentration of a substance is required in the intracellular fluid even though the extracellular fluid contains only a small concentration. This is true, for instance, for potassium ions. Conversely, it is important to keep the concentrations of other ions very low inside the cell even though their concentrations in the extracellular fluid are great. This is especially true for sodium ions. Neither of these two effects could occur by simple diffusion because simple diffusion eventually equilibrates concentrations on the two sides of the membrane. Instead, some energy source must cause excess movement of potassium ions to the inside of cells and excess movement of sodium ions to the outside of cells. When a cell membrane moves molecules or ions "uphill" against a concentration gradient (or "uphill" against an electrical or pressure gradient), the process is called active transport. 10/4/2017 77 Dr.Anu Priya J

78. ACTIVE TRANSPORT A process in which molecules move against the concentration gradient across the cell membrane with expenditure of energy. This energy is provided by ATP. 10/4/2017 78 Dr.Anu Priya J

79. Sodium potassium pump 10/4/2017 79 Dr.Anu Priya J

80. Sodium potassium pump 10/4/2017 80 Dr.Anu Priya J

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82. As with other enzymes, the Na+-K+ ATPase pump can run in reverse. If the electrochemical gradients for Na+ and K+ are experimentally increased enough so that the energy stored in their gradients is greater than the chemical energy of ATP hydrolysis, these ions will move down their concentration gradients and the Na+-K+ pump will synthesize ATP from ADP and phosphate. The phosphorylated form of the Na+-K+ pump, therefore, can either donate its phosphate to ADP to produce ATP or use the energy to change its conformation and pump Na+ out of the cell and K+ into the cell. The relative concentrations of ATP, ADP, and phosphate, as well as the electrochemical gradients for Na+ and K+, determine the direction of the enzyme reaction. For some cells, such as electrically active nerve cells, 60 to 70 percent of the cells' energy requirement may be devoted to pumping Na+ out of the cell and K+ into the cell. 10/4/2017 82 Dr.Anu Priya J

83. The Na+-K+ Pump Is Important For Controlling Cell Volume One of the most important functions of the Na+-K+ pump is to control the volume of each cell. Without function of this pump, most cells of the body would swell until they burst. The mechanism for controlling the volume is as follows: Inside the cell are large numbers of proteins and other organic molecules that cannot escape from the cell. Most of these are negatively charged and therefore attract large numbers of potassium, sodium, and other positive ions as well. All these molecules and ions then cause osmosis of water to the interior of the cell. Unless this is checked, the cell will swell indefinitely until it bursts. The normal mechanism for preventing this is the Na+-K+ pump. Note again that this device pumps three Na+ ions to the outside of the cell for every two K+ ions pumped to the interior. Also, the Guyton & Hall: Textbook of Medical Physiology, 12e [ Vish'aAlc ] tive Transport' of Substances Through Membranes 93 / 1921 membrane is far less permeable to sodium ions than to potassium ions, so once the sodium ions are on the outside, they have a strong tendency to stay there. Thus, this represents a net loss of ions out of the cell, which initiates osmosis of water out of the cell as well. If a cell begins to swell for any reason, this automatically activates the Na+-K+ pump, moving still more ions to the exterior and carrying water with them. Therefore, the Na+-K+ pump performs a continual surveillance role in maintaining normal cell volume. 10/4/2017 83 Dr.Anu Priya J

84. Electrogenic Nature of the Na+-K+ Pump page 53 page 54 The fact that the Na+-K+ pump moves three Na+ ions to the exterior for every two K+ ions to the interior means that a net of one positive charge is moved from the interior of the cell to the exterior for each cycle of the pump. This creates positivity outside the cell but leaves a deficit of positive ions inside the cell; that is, it causes negativity on the inside. Therefore, the Na+-K+ pump is said to be electrogenic because it creates an electrical potential across the cell membrane. As discussed in Chapter 5, this electrical potential is a basic requirement in nerve and muscle fibers for transmitting nerve and muscle signals. 10/4/2017 84 Dr.Anu Priya J