BIOL1040 Page 1 Membrane Structure and Function Friday, 6 March 2015 2:58 PM Cellular Membranes Fluid mosaics of lipids and proteins Phospholipids - abundant Phospholipids are amphipathic molecules (has hydrophobic and hydrophilic end) The fluid mosaic model - membrane is fluid with a 'mosaic' of proteins embedded in it Amphipathic Phospholipids Hydrophilic was to associate with water - polar Hydrophobic does not want to associate with water, would rather associate with one another - non polar Due to polarity Molecules are moving around within membrane very fast (fluid mosaic), lots of lateral movement. Flip-flop movement is very unusual as the phosphate group would have to go through the membrane, only occurs once per moth Unsaturated hydrocarbons has double bond causing kink and results in a more flexible and fluid membrane Transmembrane Proteins
BIOL1040 Page 2 Integral protein C and N terminus may not be on same side Alpha helix regions like to associate with hydrophobic lipids while hydrophilic regions like to associate with water Six Major Functions of Membrane Proteins Membrane Structure Results in Selective Permeability Lipid bilayers are impermeable to most essential molecules and ions Some permeability to water molecules and a few other small, uncharged, molecules like oxygen and carbon dioxide. Need to be nonpolar and small Lipid bilayers are not permeable to: Ions such as K+, Na+, Ca2+, Cl-, HCO3- Small hydrophilic molecules like glucose Macromolecules like proteins and RNA Passive Transport Diffusion of a substance across a membrane with no energy investment Diffusion: with time - due to random motion molecules become equally distributed i.e. to eliminate concentration gradients - provided molecules can cross the membrane No work required Diffusion across a biological membrane is passive transport (No ATP required)
BIOL1040 Page 3 Osmosis Diffusion of water through a selectively permeable membrane into another aqueous compartment containing solute at a higher concentration Water wants to be at equilibrium same number of molecules in each compartment Remember: Plasma membrane is semi-permeable Diffusion of water occcurs through water channels known as aquaporins Osmotica - things that are osmotically active, cause water to move across the membrane as they cannot move across the membrane themselves Ions (Na+, K+, Cl-, etc.) Sugars Proteins (Nutrients) Tonicity Ability of a solution to cause a cell to gain or lose water Isotonic Solution Solute concentration is the same as that inside the cell; no net water movement across the plasma membrane Hypertonic Solution Solute concentration is greater than that inside the cell; cell loses water Hypotonic Solution Solute concentration is less than that inside the cell; cell gains water
BIOL1040 Page 4 Facilitated Diffusion Passive diffusion aided by proteins In facilitated diffusion, transport proteins speed the passive movement of molecules across the plasma membrane Channel proteins provide corridors that allow a specific molecule or ion to cross the membrane Channel proteins include Aquaporin's - for facilitated diffusion of water Ion gated channels that open or close in response to a stimulus (gated channels) Transport Proteins Allow passage of hydrophilic substances across the membrane Channel proteins, have a hydropphillic channel that certain molecules or ions can use as a tunnel; e.g. aquaporin's (water) Carrier protiens, bind to molecules and change shape to shuttle them across the membrane A transport protein is specific for the substance it moves Transmembrane proteins form 'pores' through which ions and molecules can pass These pore Forming Proteins fall into two broad categories 1. Channels - facilitated diffusion 2. Transporters - facilitated diffusion or active transport
BIOL1040 Page 5 Active Transport Uses energy to move solutes against their concentration gradients Requires work - energy from ATP E.g. Na+/K+ - ATPase = sodium-potassium pump An electrogenic pump is a transport protein that generates voltage across a membrane. Sometimes a charge is carried across membrane when transported. The sodium-potassium pump is the major electrogenic pump of animal cells The main electrogenic pump of plants, fungi and bacteria is a proton pump Cotransport occurs when active transport of a solute indirectly drives transport of another solute Plants commonly use the gradient of hydrogen ions generated by proton pumps to drive active transport of nutrients into the cell Two transporters working together, one moving down concentration gradient and one
BIOL1040 Page 6 active transporting against concentration gradient. Learn how this works for Na+/K+-ATPase together with Na+-glucose transporter to drive glucose uptake Bulk Transport Occurs across the plasma membrane by exocytosis and endocytosis Exocytosis is the mechanism of neurotransmitter release from neurons Types of Endocytosis Phagocytosis Engulfing particles Pinocytosis Cells drinking Receptor-mediated endocytosis
BIOL1040 Page 8 Cell Communication and Receptor Families Friday, 13 March 2015 2:22 pm Local vs. long-distance signalling If something get released from a cell it can act very close to the cell it is released from or act very far away Autocrine signalling occurs when secreting cells act upon the cell that released it Synaptic signalling is localised even though signal has come from a long way away. Chemical does not travel a long distance Signalling molecules and receptor are specific to one another 3 Stages of Cell Signalling Hormone/ Ligand/ Agonist act via receptors Signalling molecule for an intracellular receptor must be able to diffuse across the membrane Receptor Types Arranged from fastest to slowest Plasma Membrane Receptors Ion channel receptors: Na+ channel opened by ligand - e.g. nictoninc receptors - fast neurotransmission G-Protein-coupled receptors: 7 Transmembrane-spanning regions All aspects of physiology and pharmacology Very large family Work in seconds Tyrosine Kinase Linked Receptors e.g. insulin receptor
BIOL1040 Page 9 Metabolism, cell growth, cell reproduction Intracellular receptors Steroid receptors Ion Channel Receptors When ligand binds to the receptor, gate opens allowing flow of specific ions rapidly changing the concentration of the ions either side of the membrane Once ligand dissociates, gate will close again G-Protein Coupled Receptors 7 transmembrane spanning domains (7 TMDs) The largest family of receptors: >1000 members in human genome 150 orphans >50% of current drugs target GPCRs Activated by a variety of stimuli: Light, ions (e.g. Ca2+), odorants, gustative molecules, neurotransmitters, hormones, peptides, proteins GPCRs interact with heterotrimeric (3 peptide changes, alpha, beta, gamma) G proteins to control the activity of enzymes, ion channels and intracellular signal transduction pathways When signalling molecule bonds to G protein-coupled receptor (extracellular side) it activates the receptor causing it to change shape The G protein-coupled receptor then binds to an inactive G-protein causing GTP to be replaced by GDP activating the protein Activated G-protein dissociates from the receptor, diffuses along the plasma membrane and binds to adenylyl cyclase which catalyses the conversion of ATP to camp (cyclic adenosine monophosphate) camp acts as a second messenger and activates another protein, usually protein kinase A, leading to a cellular response
BIOL1040 Page 12 Role of Protein Phosphorylation Insulin Receptors: Tyrosine Kinase Receptors Two receptors joint together Do not worry about detail, just note the amount of phosphorylation Glucose transporters move to cell membrane and allow glucose to move into the cell More phosphorylation will produce glycogen Steroid Hormone Receptor
BIOL1040 Page 14 Macromolecules Thursday, 19 March 2015 9:00 am Overview All living things are made up of four classes of large biological molecules: carbohydrates, lipids, proteins and nucleic acids Within cell, small molecules are joined together to form larger molecules Macromolecules are large molecules composed of thousands of covalently connected atoms Molecular structure and function are inseparable Macromolecules They are polymers built from monomers Complex molecules A polymer is a long molecule consisting of many similar building blocks These small building-block molecules are called monomers Three of the four classes of life's organic molecules are polymers: Carbohydrates Proteins Nucleic Acids The synthesis and breakdown of polymers A condensation reaction, or dehydration reaction, occurs when two monomers bond together and lose a water molecule Enzymes are macromolecules that speed up the dehydration process Polymers are disassembled to monomers by hydrolysis, a reaction that is essentially the reverse of the dehydration reaction Carbohydrates serve as fuel and building material Carbohydrates include sugars and the polymers of sugars The simplest carbohydrates are monosaccharides or single sugars Carbohydrate macromolecules are polysaccharides, polymers composed of many sugar building blocks Sugars Glucose (C 6 H 12 O 6 ) is the most common monosaccharide Monosaccharides are classified by: The location of the carbonyl group (as aldose or ketose) The number of carbons in the carbon skeleton Structure and Classification of Monosaccharides