Cystic fibrosis - just one small change in a protein

Fluid-Mosaic Model

• Membranes consist of a phospholipid bilayer studded with proteins, polysaccharides, lipids
• The lipid bilayer is semipermeable - H2O and some small, uncharged, molecules (O2, CO2) can pass through
• Phospholipids have two parts
  • "Head": hydrophilic → attracts and mixes with H2O
  • Two "fatty acid tails": hydrophobic

Passive Transport

Diffusion

• Uses energy from moving particles (kinetic energy)
• Substances move down their conc. gradient until the conc. are in equilibrium
• Fick's law → rate of diffusion across an exchange surfaces (e.g. membrane, epithelium) depends on
  • Surface area across within diffusion occurs (larger)
  • Thickness of surface (thinner)
  • Difference in conc. gradient (larger)
  • (surface area * difference in conc.) / thickness of surface
• Microvilli
  • Extensions of the plasma membrane
  • They increase the surface area of the membrane
  • Accelerate the rate of diffusion
• Temperature increases rate of diffusion due to increasing K.E. (kinetic energy)

Facilitated Diffusion

• Transmembrane proteins form a water-filled ion channel
  • Allows the passage of ions (Ca2+, Na+, Cl-) down their conc. Gradient
  • NB: this is a passive process → no ATP required
  • Some channels use a gate to regulate the flow of ions
  • Selective permeability → not all molecules can pass through selective channels
• Transport mechanism
  • Carrier protein binds to substrate (specific molecule)
  • Molecule changes shape
  • Release of the diffusing molecule (product) at the other side of the membrane
• Example
  • If you want to move a muscle, a nerve impulse is sent to this muscle
  • The nerve impulse triggers the release of a neurotransmitter
  • Neurotransmitter binds to a specific transmembrane protein
  • The protein opens channels that allow the passage of Na+ across the membrane
  • In this specific case, this causes muscle contraction
  • These Na+ channels can also be opened by a change in voltage

Osmosis

• Special term used for the diffusion of water through a differentially permeable cell membrane
• Water is polar and able to pass through the lipid bilayer
• Transmembrane proteins that form hydrophilic channels accelerate osmosis, but water is still able to get through membrane without them
• Osmosis generates pressure called osmotic pressure
  • Water moves down its conc. gradient
  • When pressure is equal on both sites net flow ceases (equilibrium)
  • The pressure is said to be hydrostatic (water-stopping)

Water Potential

• Measurement of ability or tendency of water molecules to move
• Water potential of distilled water is 0, other solutions have a negative water potential
• Hypotonic: solution with a lower conc. of solute / gains water by osmosis
  • Solution is more dilute
  • Cells placed in a solution which is hypotonic will grow as water moves in
  • Red blood cells will swell and burst if it is in a hypotonic solution
  • Plant cells are unable to burst due to their strong cellulose wall
• Hypertonic: solution with a higher conc. of solutes / loses water by osmosis
  • Cells will shrink in hypertonic solutions (eg red blood cells)
• Isotonic: solutions being compared have equal conc. of solutes
  • Cells which are in an isotonic solution will not change their shape
  • The extracellular fluid of the body is an isotonic solution
• Molecules collide with membrane / creates pressure, water potential
• More free water molecules, greater water potential, less negative
• Solute molecules attract water molecules which form a "shell" around them
  • water molecules can no longer move freely
  • less "free water" which lowers water potential, more negative

Active Transport

• Movement of solute against the conc. gradient, from low to high conc.
• Involves materials which will not move directly through the bilayer
• Molecules bind to specific carrier proteins / intrinsic proteins
• Involves ATP by cells (mitochondria) / respiration
  • Direct active transport - transporters use hydrolysis to drive active transport
  • Indirect active transport - transporters use energy already stored in gradient of a directly-pumped ion
• Bilayer protein transports a solute molecule by undergoing a change in shape (induced fit)
• Occurs in ion uptake by a plant root; glucose uptake by gut cells

Ribosomes

• 20-30nm in size
• Small organelles often attached to the ER but also found in the cytoplasm
• Large (protein) and small (rRNA) subunits form the functional ribosome
  • Subunits bind with mRNA in the cytoplasm
  • This starts translation of mRNA for protein synthesise (assembly of amino acids into proteins)
• Free ribosomes make proteins used in the cytoplasm. Responsible for proteins that
  • go into solution in cytoplasm or
  • form important cytoplasmic, structural elements
• Ribosomal ribonucleic acid (rRNA) are made in nucleus of cell

Endoplasmic Reticulum (ER)

• Rough ER
  • Have ribosomes attached to the cytosolic side of their membrane
  • Found in cells that are making proteins for export (enzymes, hormones, structural proteins, antibodies)
  • Thus, involved in protein synthesise
  • Modifies proteins by the addition of carbohydrates, removal of signal sequences
  • Phospholipid synthesis and assembly of polypeptides
• Smooth ER
  • Have no ribosomes attached and often appear more tubular than the rough ER
  • Necessary for steroid synthesis, metabolism and detoxification, lipid synthesis
  • Numerous in the liver

Golgi Apparatus

• Stack of flattened sacs surrounded by membrane
• Receives protein-filled vesicles from the rough ER (fuse with Golgi membrane)
• Uses enzymes to modify these proteins (e.g. add a sugar chain, making glycoprotein)
• Adds directions for destination of protein package - vesicles that leave Golgi apparatus move to different locations in cell or proceed to plasma membrane for secretion
• Involved in processing, packaging, and secretion
• Other vesicles that leave Golgi apparatus are lysosomes

Endocytosis and Exocytosis

• Substances are transported across plasma membrane in bulk via small vesicles
• Endocytosis
  • Part of the plasma membrane sinks into the cell
  • Forms a vesicle with substances from outside
  • Seals back onto the plasma membrane again
  • Phagocytosis: endocytosis brings solid material into the cell
  • Pinocytosis: endocytosis brings fluid materials into the cell
• Exocytosis
  • Vesicle is formed in the cytoplasm // may form from Golgi apparatus
  • Moves towards plasma membrane and fuses with plasma membrane
  • Contents are pushed outside cell
  • Insulin is secreted from cells in this way

Mitochondria

• 1µm in diameter and 7µm in length
• Mostly protein, but also contains some lipid, DNA and RNA
• Power house of the cell
• Energy is stored in high energy phosphate bonds of ATP
• Mitochondria convert energy from the breakdown of glucose into adenosine triphosphate (ATP)
• Responsible for aerobic respiration
• Metabolic activity of a cell is related to the number of cristae (larger surface area) and mitochondria
• Cells with a high metabolic activity (e.g. heart muscle) have many well developed mitochondria