Chapter 2- Membrane physiology.power pointspptx

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1. CHAPTER TWO MEMBRANE PHYSIOLOGY 1

2. Cell Membrane A thin, pliable, elastic structure that envelops the cell Only 7.5 to 10 nanometers thick General function: Physical isolation Regulation of exchange with the environment Communication b/n the cell and its environment Structural support 2

3. Major components: 1. Phospholipids (25%) Form the basic structure of cell membrane Amphipathic – have polar (water- soluble) & non polar (water- insoluble) regions In aqueous solution: Hydrophilic head: oriented towards the outer surface (interact with water) Hydrophobic tails: oriented themselves into the center away from water They form double phospholipid layers = Lipid bilayer Lipid bilayer – creates a semi-permeable barrier 3

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5. Gases (O 2 & CO 2 ), FA molecules (lipophilic) are readily cross the membrane Phospholipids are not held together by chemical bonds Make the lipid bilayer is not rigid structure Have contribution for membrane fluidity 2. Cholesterol (13%) Inserted in b/n the phospholipid molecules Prevent FA chains form packing together & crystallizing ≠ contributes to the fluidity as well as stability of the membrane 5

6. 3. Membrane proteins (55%) Two types: Integral (transmembrane) : embedded within & span the width of the membrane Extrinsic (peripheral) : on the internal or external surface of the membrane Function : They form channels, chemical receptors, carrier molecules, antigens, enzymes 6 Structure of cell membrane

7. 4. Carbohydrates (3%) Found in small amount Located on the outer surface of cells + proteins  glycoproteins + lipids  glycolipids form coating => glycocalyx Function: Repelling negatively charged substances Cell to cell attachment Receptors Immune reactions (distinguishing b/n self cells & foreign cells) 7

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9. Summary on Cell membrane Components 9

10. Membrane Transport Permeability of cell membrane depends on: a) the properties of particles : Lipid solubility, size , charge b) the presence of channels & transporters Uncharged + nonpolar molecules  permeate CM Example: CO 2 , O 2 and FAs Charged + polar molecules  can not permeate CM Example: Ions (Na + , K + ), glucose & proteins For small, water soluble particles => channels For large & lipid insoluble particles => carriers 10

11. Transport Across Cell Membranes Passive :- occur down conc. or electrochemical gradient (“downhill”) Does not require metabolic energy Simple diffusion, facilitated diffusion & osmosis Active transport :- occur against conc. or electrochemical gradient (“uphill”) Requires metabolic energy in the form of ATP 1 o active transport, 2 o active transport & Vesicular transport : endocytosis & exocytosis NB : Facilitated diffusion and active transport are carrier-mediated 11

12. Simple Diffusion Not carrier mediated Occur down conc. or electrochemical gradient (“downhill”) Does not require metabolic energy The rate at which a material diffuses through a membrane (flux) is given by Fick's law of diffusion 12

13. 13 Simple diffusion can occur across the CM through: (a) (b) Intermolecular spaces Membrane openings (Channels)

14. Osmosis Net diffusion of water down its concentration gradient through a selectively permeable membrane Water moves toward an area of higher solutes conc. or from high osmotic potential to low osmotic potential Water molecules are strongly polar, but they are small. So, they can readily permeate the cell membrane However, this type of water movement across the membrane is relatively slow Aquaporins , which are channels specific for the passage of water (aqua means “water”), greatly increases membrane permeability to water 14

15. Tonicity refers to the effect the conc. of non-penetrating solutes in a solution has on cell volume 1 . Isotonic solution Has the same conc. of non-penetrating solutes as normal body cells do. No water enters or leaves the cell by osmosis Cell volume remains constant 2 . Hypotonic solution A solution with a below-normal conc. of non-penetrating solutes (and therefore a higher conc. of water) Water enters the cells by osmosis, causes them to swell, rupture or lyse 15

16. 3 . Hypertonic solution a solution with an above-normal conc. of non-penetrating solutes (and therefore a lower conc. of water) The cells shrink as they lose water by osmosis Cell decreases in volume with a crenated, or spiky, shape 16

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18. Carrier-mediated transport A carrier protein spans the thickness of the plasma membrane and can change its conformation (shape) so that specific binding sites within the carrier are alternately exposed to the ECF and the ICF. Characteristics Specificity: Carrier proteins bind only with select substances that fit into its binding site 2. Saturation: Carrier binds substances until their maximum capacity. This limit is known as the transport maximum ( Tm ) When the Tm reached, the carrier is saturated 18

19. Fig. : Comparison of carrier-mediated transport and simple diffusion down a concentration gradient 19

20. 3. Competition Different substances with similar chemical structures may be able bind to the same carrier protein & the therefore compute for transport across the membrane E.g. AAs glycine and alanine 20

21. Facilitated Diffusion Occurs down an electrochemical gradient(“downhill”), similar to simple diffusion Does not require metabolic energy and therefore is passive. Is more rapid than simple diffusion Is carrier-mediated and therefore exhibits specificity, saturation, and competition E.g . Glucose transport by the glucose transporter (GLUT) across intestinal epithelium The transport of glucose into RBCs, muscles and adipose tissue in the presence of insulin 21

22. 22 Mechanism of facilitated diffusion

23. Active Transport Uses carrier proteins Carriers transport the sub. uphill against its conc. gradient Requires energy Two forms: 1 o active transport, 2 o active transport 1 o active transport Occurs against an electrochemical gradient(“uphill”). Requires direct input of metabolic energy in the form of ATP and therefore is active. Is carrier-mediated and therefore exhibits specificity, saturation, and competition 23

24. Examples: 1. Na + /K + -ATPase (or Na + –K + pump) In cell membranes Transports Na + from ICF to ECF and K + from ECF to ICF It maintains low intracellular [Na + ] and high intracellular [K + ] Both Na + and K + are transported against their electrochemical gradients The usual stoichiometry is 3 Na + /2 K + Produces net movement of positive charge out of the cell ( an electrogenic pump ) This electrical potential is a basic requirement in nerve and muscle fibers for transmitting electrical signals Specific inhibitors of Na + , K + -ATPase are the cardiac glycoside drugs ouabain and digitalis 24

25. 2. Ca 2+ -ATPase (or Ca 2+ pump) In the sarcoplasmic reticulum (SR) or cell membranes Transports Ca 2+ against an electrochemical gradient. Sarcoplasmic and endoplasmic reticulum Ca 2+ -ATPase is called SERCA 3. H + /K + -ATPase (or proton pump) It is present in the cells of the gastric mucosa ( in gastric parietal cells ) and renal tubules where it causes the secretion of H + Transports H + into the lumen of the stomach against its electrochemical gradient It is inhibited by proton pump inhibitors, such as omeprazole 25

26. Secondary Active Transport The transport of two or more solutes is coupled One of the solutes (usually Na + ) is transported “downhill” and provides energy for the “uphill” transport of the other solute(s) Metabolic energy is not provided directly, but indirectly from the Na + gradient that is maintained across cell membranes. Thus, inhibition of Na + ,K + -ATPase will decrease transport of Na + out of the cell, decrease the transmembrane Na + gradient, and eventually inhibit secondary active transport If the solutes move in the same direction across the cell membrane, it is called cotransport, or symport 26

27. Examples: Na + – amino acids, Na + –glucose cotransport in the small intestine Na + –K + –2Cl – cotransport in the renal thick ascending limb If the solutes move in opposite directions across the cell membranes, it is called counter -transport , exchange , or antiport . Examples : Na + –Ca 2+ exchange (in heart muscle cell) Na + –H + exchange (in renal tubules) 27

28. Vesicular Transport Allows the transport of macromolecules and multimolecular particles between the ECF and ICF Requires energy expenditure by the cell Energy is needed to accomplish vesicle formation and vesicle movement within the cell There are two mechanisms: endocytosis & exocytosis Endocytosis Engulfing of materials by invaginating (folding inward) the outer part of the membrane 28

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30. Types : Phagocytosis : Large multimolecular particles are internalized Solid molecules (bacteria, tissue debris) surrounded by CM & taken up “cell eating” Only a few specialized cells are capable of phagocytosis Eg . Neutrophils & macrophages They extend surface projections known as pseudopods (“false feet”) that surround or engulf the particle and trap it within an internalized vesicle known as a phagosome A lysosome fuses with the membrane of the phagosome and releases its hydrolytic enzymes into the vesicle 30

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32. Pinocytosis: droplets of ECF is taken up nonselectively “cell drinking” 32

33. Receptor-Mediated Endocytosis Highly selective process that enables cells to import specific large molecules that it needs from its environment Triggered by the binding of a specific target molecule such as a protein to a surface membrane receptor specific for that molecule E.g. Cholesterol complexes, vitamin B 12 , insulin, and iron 33

34. Exocytosis The reverse of endocytosis Molecules within cells are packaged into secretory vesicles, which then fuse with the plasma membrane and release their contents into the extracellular fluid Example: Neurotransmitter 34

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