1. UNIT 6. BIOMEMBRANES AND TRANSPORT

2.  Introduction.  Lipids structures spontaneously formed in water.  Fluid Mosaic model.  Properties of the membranes.  Membranes asymmetry.  Membrane proteins.  Membrane carbohydrates.  Membrane transport: types of transport.  Ionophores.  Summary of the transport systems. OUTLINE

3. INTRODUCTION: Thin laminar structures characterised by their stability and flexibility. The plasma membrane separates the cytoplasm from the surroundings. They are responsible for: - Exclusion of certain toxic ions and molecules rom the cell - The accumulation of cell nutrients - Energy transduction. - Cell locomotion, reproduction, signal transduction processes and interactions with molecules or cells in the vicinity. They are not passive borders. Biological membranes contain proteins with specific functions.

4. Molecule containing one nonpolar tail. Molecule containing two nonpolar tails. Bilayer Water body Liposomes LIPIDS STRUCTURES SPONTANEOUSLY FORMED IN WATER: Micelles

5. FLUID MOSAIC MODEL: It describes membrane dynamics: - Lipid bilayer is the main structural skeleton. - Proteins: integral membrane proteins and peripheral membrane proteins. All the kingdoms, species, tissues and organelles are characterised by the membrane lipid composition. Different membranes present different protein/lipids ratio.

6. Nonpolar acyl chains Polar groups Glycolipid Peripheral protein Integral protein (one transmembrane helix) Peripheral protein covalently link to a lipid Integral protein (several transmembrane helixes) Lipid bilayer Oligosaccharide side chain FLUID MOSAIC MODEL:

7. PROPERTIES OF THE MEMBRANES:  The membranes can recover their structures: The membranes are able to spontaneously reorganise the structure after suffering any kind of damage.  The membranes have fluid like properties: Although phospholipids are interacting by means of hydrophobic interactions, the lipids area highly mobile in the plane of the bilayer. Lateral diffusion or rotation are the main phospholipid diffusion processes in a lipid bilayer. However, the transverse diffusion (flip-flop) is an extremely rare event.

8. PROPERTIES OF THE MEMBRANES: The Fluidity of the membranes depends on: Temperature: The increase of the temperature promotes molecular diffusion, and so that, promotes membrane fluidity. Unsaturations: The higher saturated phospholipids concentration the higher interaction between phospholipids. As a consequence of that, the fluiditydecrease.

9. PROPERTIES OF THE MEMBRANES: Length of the hydrophobic chains: Long chain phospholipids establish higher number of interactions with other lipids chains. Short chain phospholipids promotes membrane fluidity (they present higher mobility). Cholesterol regulates the fluidity: In animal cells, the fluidity of the membranes can be regulated by cholesterol. In general, it decreases membrane fluidity because its rigid steroid ring system interferes with the motions of the fatty acid side chains in other membrane lipids.

10. PROPERTIES OF THE MEMBRANES: Segmentos de cadenas rígidas Segmentos de cadenas flexibles Segmentos de cadenas rígidas Bicapa lipídica.

11. PROPERTIES OF THE MEMBRANES: Ca 2+ decreases the membrane fluidity: Ca 2+ is able to interact (charge-charge interactions) with phosphate groups belonging to phospholipids. These interactions promote highly compact structures (decreasing membrane fluidity).

12. PROPERTIES OF THE MEMBRANES: Cells can modify the lipids composition at different temperatures to keep the fluidity of the membrane constant. Bacteria cultures at low temperatures: high unsaturated fatty acid concentration (less saturated fatty acid).

13. MEMBRANES ASYMMETRY : Asymmetric distribution of phospholipids between the inner and the outer monolayers of the erythrocyte plasma membrane. Plasma membrane lipids are asymmetrically distributed between the two monolayers of the bilayer:

14. Proteins differ in their association with the membrane: - They constitute around 50% of the overall membrane mass. - Proteins are involved in solute transport, adhesion molecules, enzymatic reactions (some of them are enzymes) or signal receptor. Membrane proteins are classified as integral membrane proteins or peripheral membrane proteins. MEMBRANE PROTEINS:

15. Integral membrane proteins are firmly associated with the lipid bilayer, and are removable only by agents that interfere with hydrophobic interactions, such as detergents, organic solvents or denaturants.

16. MEMBRANE PROTEINS: Peripheral membrane proteins associate with the membrane through electrostatic interactions and hydrogen bonding with the hydrophilic domains of integral proteins and with the polar head groups of membrane lipids (the do not cross the bilayer). Protein diffuse laterally in the bilayer because of the bilayer fluidity. These proteins can be released by relatively mild treatments: pH o salt concentrations changes (non covalent intearctions) or phospholipases (covalent interactions)

17. Not all integral membrane proteins are composed of transmembrane  helices. Another structural motif common in bacterial membrane proteins is  barrel. Integral membrane protein. Trnasbilayer disposition of glycophorin in an erythrocyte. Bacteriorhodopsin MEMBRANE PROTEINS:

18. MEMBRANE CARBOHYDRATES: Oligosaccharides covalently bounded to lipids (glycolipids) or proteins (glycoproteins). Major monosaccharides: glucose, galactose, mannose, neuraminic acid, N-acetylgalactosamine or N- acetylglucosamine. They are exposed on the extracellular surface of the membrane and they are involved in cell recognition, cell adhesion or they act as receptors.

19. MEMBRANE TRANSPORT: TYPES OF TRANSPORT. Cells are opened systems exchanging matter and energy with the surroundings. Charged molecules at physiological pH require a proper molecular environment to establish interactions. So, cells need structures to promote the mobility of these molecules.

20.  Classification: 1. Protein non-dependent transport: - Simple diffusion. 2. Protein-dependent transport: - Facilitated diffusion: No requires energy. Two types:  Carrier proteins.  Channels. - Active transport: energy dependent. Specialised carrier proteins are involved. Two types:  Primary active transport.  Secondary active transport. MEMBRANE TRANSPORT: TYPES OF TRANSPORT.

21. MEMBRANE TRANSPORT: TYPES OF TRANSPORT.c Primary active transport: energy from light or ATP hydrolysis. Secondary active transport: against electrochemical gradient, driven by ion moving down its gradient.

22. Transport systems of the base of the solutes transported and the direction of the transport: - Uniport. - Simport or Parallel cotransport. - Antiport or Antiparallel cotransport. MEMBRANE TRANSPORT: TYPES OF TRANSPORT.

23.  SIMPLE DIFUSSION: Down concentration gradient. No saturated by the substrates. No energy dependent. No carrier proteins. Examples: CO 2, O 2, H 2 O. MEMBRANE TRANSPORT: TYPES OF TRANSPORT.

24. Transmembrane proteins allow the transpot of charged or high molecular mass solutes across the cellular membranes. Two types: CHANNELS and CARRIER PROTEINS. Carrier proteins: high stereospecificity, saturables and they suffer conformational changes. Channels: less stereospecificity and non saturables. MEMBRANE TRANSPORT: TYPES OF TRANSPORT.

25. Topology representation of the glucose transporter (GLUT1)  FACILITATED DIFFUSION: Down electrochemical gradient. i.e. Glucose transport into erythrocytes: MEMBRANE TRANSPORT: TYPES OF TRANSPORT.

26.  FACILITATED DIFFUSION: Kinetics of glucose transport into erythrocytes: Substrate = glucose outside the cell (S out ) Product = glucose inside the cell (S in ) Enzyme = transporter v 0 = V máx [S] out K t +[S] out MEMBRANE TRANSPORT: TYPES OF TRANSPORT.

27.  PRIMARY ACTIVE TRANSPORT: Against electrochemical gradient. I.e. sodium-potassium pump = Na + -K + ATPase. MEMBRANE TRANSPORT: TYPES OF TRANSPORT.

28.  SECONDARY ACTIVE TRANSPORT: I.e. Intestinal epithelial cells: glucose is cotransported with Na + across the apical plasma membrane into the epithelial cell. It moves through the cell to the basal surface, where it passes into the blood via GLUT2 (passive glucose uniporter). Na + -K + ATPase pumps Na + outward to maintain the Na + gradient that drives glucose uptake. MEMBRANE TRANSPORT: TYPES OF TRANSPORT.

29.  Energetics of pumping by symport:  A solute is transport from a region where the solute concentration is C 1 to another region with solute concentration equal to C 2, (bounds are not broken or established), so  G 0 ’ = 0:  G t = RT ln (C 2 /C 1 )  Uncharged solutes.  If the solute is an ion, its transport generates en electrical potential: Electrogenic transport. The energy required to transport an ion is the result of the chemical and electrical gradients:  G t = RT ln (C 2 /C 1 ) + Z F  Z = ion change F = Faraday constant  = transmembrane electrical potential MEMBRANE TRANSPORT: TYPES OF TRANSPORT.

30. Channels (strict ionophores) (i.e. gramicidine) Movil carriers (i.e. valinomycin)  They collapse ion gradients across cellular membranes.  They are ion carriers.  They increase the membrane permeability.  Cell death is caused by secondary transport inhibition.  Types: TRANSPORT ACROSS MEMBRANES. IONOPHORES: K+K+

31. SIMPLE DIFFUSION (nonpolar compounds only, down concentration gradient) FACILITATED DIFFUSION (down electrochemical gradient) PRIMARY ACTIVE TRANSPORT (against electrochemical gradient) SECONDARY ACTIVE TRANSPORT (against electrochemical gradient, driven by ion moving down its gradient) IONOPHORE-MEDIATED ION TRANSPORT (down electrochemical gradient) ION CHANNEL (down electrochemical gradient; may be gated by a ligand or ion) MEMBRANE TRANSPORT. SUMMARY: