Compendium 5 Notes PDF

Compendium 5 Notes Lecture 1 The plasma membrane - Forms a complete boundary around the cell - Composed of phospholipids, proteins and cholesterol - The bi-molecular layer of phospholipids forms the basic structure - Cholesterol molecules are inserted between the phospholipid molec...

Compendium 5 Notes Lecture 1 The plasma membrane - Forms a complete boundary around the cell - Composed of phospholipids, proteins and cholesterol - The bi-molecular layer of phospholipids forms the basic structure - Cholesterol molecules are inserted between the phospholipid molecules at regular intervals to provide rigidity - Also integrates both integral (span across the whole width of the membrane) and peripheral (only on the inside or outside) proteins Composition of the plasma membrane - The lipid bilayer serves as a highly impermeable barrier to most "charged (polar)" and "non lipid soluble" substances - However integral proteins acting as pores, channels or carriers allow these substances to cross the membrane - Plasma membranes are selectively permeable, some things can pass though and some things can't - Permeability is a function of several factors: 1. Solubility in lipids 2. Driving forces (up or down gradient) 3. Molecular size - Transport can be active (usually against gradient) or passive (usually moving down a gradient) - Water soluble substances require specialised transmembrane proteins to function as channels or carriers Transport across the membrane - 3 types of passive transport 1. Diffusion through the lipid bilayer (lipid soluble)(simple diffusion) 2. Diffusion through the pores/ion channels (water soluble)(channel mediated) 3. Facilitated diffusion (water soluble)(carrier mediated) - Active transport requires ATP (cellular energy) - Water molecules penetrate the membrane by diffusion through the lipid bilayer or through aquaporins (transmembrane proteins) that function as water channels - The movement of water through the membrane is called osmosis which is defined as "the movement of water from a low solute concentration to a high solute concentration" Diffusion through the lipid bilayer - Lipid soluble substances for example respiratory gases, lipids, small alcohols and urea can diffuse across the lipid bilayer (O2/CO2) - A concentration gradient is usually the driving force for this type of transport Diffusion across the lipid bilayer - water soluble substances like ions, small sugars, amino acids and water need integral membrane proteins to move across the cell membrane 1. small ions (channels) 2. water (channels) 3. sugars and amino acids (facilitated diffusion) - again a concentration of electrical gradient is often the driving force of this type of transport facilitated diffusion - in facilitated diffusion, a solute binds to a specific transporter on the side of the membrane and is released on the other side - solutes that move this way include glucose (out of the cell) an fructose (into the cell) - rate of movement depends upon... - steepness of the concentration gradient - number of transporter proteins in the membrane (transport maximum) gated protein channels - some membrane proteins are ion channels - an electrochemical gradient is often the driving force - ion channels are selective and specific (usually specific to an ion and will only let that ion pass through) - some channels formed by transport proteins are continuously open but others only open transiently (gated protein channels) - transport occurs at a faster rate in comparison to facilitated diffusion active transport - active transport is an energy requiring process that moves solutes against a concentration gradient - in primary active transport energy is derived directly from ATP - metabolic (ATP Hydrolysis) - the most common primary active transport mechanism is the sodium-potassium ion pump - 40% of cellular ATP goes towards running these - all cells have 1000 of them - maintains the low concentration of Na+ and a high concentration of K+ in the cytosol - operates continually - in secondary active transport energy is derived indirectly from ATP - cotransport of Na+ or H+ ions - the energy is stored in Na+ or H+ concentration gradients which are used to drive other substances against their own concentration gradients - plasma membranes contain several antiporters and symporters that are powered by the sodium ion gradient created by the sodium potassium pump membrane transport of complex molecules 1. exocytosis - movement of large molecules out of the cell - occurs in secretory cells - secretions in vesicles (membrane packets) -- vesicles fuse with cell membrane, e.g. neurotransmitter secretion at the synapse - process: - a secretory vesicle moves towards the plasma membrane - the secretory vesicle fuses with the plasma membrane - the secretory vesicles contents are released into the extracellular fluid 2. endocytosis - movement of large molecules and particles into the cell - pinocytosis: engulfing small particles and fluids - phagocytosis: engulfing large particles - receptor mediated endocytosis: the movement of specific substances into the cell involving the caveolae regions of the cell membrane - process: - receptor molecules on the cells surface bind to molecules to be taken into the cell - the receptors and the bound molecules are taken into the cell as a vesicle begins to form - the vesicle fuses and separates from the plasma membrane lecture 2 composition of the plasma membrane - Water molecules penetrate the membrane by diffusion through the lipid bilayer or through aquaporins (transmembrane proteins) that function as water channels - The movement of water through the membrane is called osmosis which is defined as "the movement of water from a low solute concentration to a high solute concentration" Osmosis: driving forces - The driving force is not the water concentration but the concentration of the solutes dissolved within it - Water is the solvent for all solutes and is present at a very high concentration (56molar) - This means that when solutes are dissolved in water their concentration changes very little - when a solute dissolves in water it displays an osmotic pressure or drawing power to encourage water to move towards it - therefore where possible water always moves to the solution with the highest osmotic pressure (highest solute concentration) - hence the definition "the movement of water from a low solute concentration to a high solute concentration" - osmosis is the net movement of water through a selectively semipermeable membrane osmosis occurs only when the membrane is permeable to water but not to certain solutes - the osmotic pressure that a solution exerts is proportional to the number of osmotically active particles in the solution - the osmotic pressure of a solution is proportional to the concentration of the solute particles that cannot cross the membrane Tonicity - Tonicity is a measure of a solutions ability to change the volume of cells by altering their water contents - In an isoto nic solution there is no net movement of water so cells maintain their normal shape - In a hypertonic solution cells loose water and are in danger of shrinking or becoming dehydrated - In a hypotonic solution cells gain water so are in danger of swelling and bursting (maybe like red blood cells??) - There are important medical uses of isotonic, hypertonic and hypertonic solutions - Tonicity can be demonstrated with red blood cells when placed in different saline solutions - In an isotonic solution they maintain their shape - In a hypotonic solution they undergo haemolysis (water floods the cell till the cell bursts) - In a hypertonic solution they undergo crenation (water leaves the cell leading to dehydration and deformity) Lecture 3 Introduction to glycolysis - 3 major destinations for the nutrients we eat 1. Energy 2. Structural or functional molecules 3. Storage compounds - Most energy is derived from the oxidisation of CHO fat and protein - CHO} - Fat }\-\--+O2\-\-\-\-- CO2, H2O + energy (ATP + heat) - Protein } - About 60-70% of the energy produced is lost as heat - The remainder is stored as chemical energy (ATP) Metabolic reactions - Metabolism: all chemical reactions in the body - Catabolism: chemical reactions that break down complex organic molecules - Anabolism : chemical reactions that build up simple molecules into complex - All molecules have energy stored between their bonds - All chemical reactions depend on the transfer of a small amount of energy from one molecule to another - This transfer is usually performed by ATP Adenosine triphosphate - A molecule for the temporary storage of energy - 3 phosphate groups attached to an adenine base and a 5c sugar (ribose) - ATP is used for... - Muscle contraction - Active transport - Movement of structures within a cell - Large amounts of energy are released when the terminal phosphate bond is hydrolysed (broken) Stages in energy generation - First stage: large molecules are broken into smaller units - Proteins -- peptides and amino acids - Fats -- glycerol and fatty acids - Polysaccharides -- simple sugars - Second stage - Smaller units are degraded into a few key simple compounds that play a central role in metabolism - Third stage - Citric acid (Krebs cycle) - Oxidative phosphorylation Carbohydrate metabolism - During digestion polysaccharides and disaccharides are converted into monosaccharides (primarily glucose) - CHO metabolism is mostly concerned with glucose metabolism - The oxidisation of glucose is shown by the following reaction C6H12O6 + 6O2 -\> H2O + CO2 + 36ATP + heat - Glucose is catabolised in 3 different ways - Glycolysis - Glucose -\> pyruvic acid -\> mitochondria -\> processed through krebs cycle - Krebs cycle - The electron transport chain and oxidative phosphorylation Cellular respiration - Metabolic pathways synthesise ATP - Anerobic: ATP production in the absence of O2 is glycolysis - Glycolysis - Production of acetyl CoA as a transitional step - Aerobic: ATP production using O2 is oxidative phosphorylation - Krebs cycle - Electron transport chain - Fuel + O2 -\> CO2 + H2O + Energy (ATP + Heat) Glycolysis - Overall equation - Initial steps - Activate the glucose (2 phosphate groups){uses 2 molecules of ATP} - Later in glycolysis - 4ATP (+ 2NADH2) energy is liberated - Energy yield: {4-2} = 2ATP + 2NADH2 (you made for but required 2 to do it) - Although it doesn't seem like much its been made in the absence of O2 so its 'budget friendly - Phase 1: sugar activation - 2 ATP molecules are used to activate the glucose (fructose\[type of sugar\] - 1, 6 \[refering to the carbons on the ring\] -- bisphosphate\[has phosphates on it\]) - Phase 2: sugar cleavage - 6C sugar is split into 2 x 3C sugars - Each 3C sugar has a phosphate group - Inorganic phosphate groups (Pi) are attached to each oxidised sugar fragment - Phase 3: oxidisation and ATP formation - The phosphates are split from the sugar and captured by ADP to form 4ATP molecules - The remaining 3C sugars are pyruvic acid - The final products include 2 pyruvic acid molecules, 2NADH and H molecules (reduced NAD) - A net gain of 2 ATP molecules - If O2 is available the pyruvic acid prepares to enter the krebs cycle - If O2 is not available the pyruvic acid accepts H2 from NADH2 to form lactic acid (maintains sullies of NAD for glycolysis to continue) - Pyruvic acid - The fate of pyruvic acid depends on the availability of O2 - When O2 is not available - Pyruvic acid is reduced to lactic acid - lactic acid rapidly diffuse out of the cell and into the blood - liver cells remove lactic acid from the blood and convert it back to pyruvic acid - When O2 is available - Pyruvic acid procedes to the krebs cycle in the mitochondrion Lecture 4 Formation of Acetyl coenzyme A - Pyruvic acid enters the mitochondria and undergoes decarboxylation (remove CO2) - Pyruvate dehydrogenase converts 3C pyruvic acid to the compound 2C acetyl group plus CO2 - 2C acetyl group is attached to coenzyme A to form acetyl coenzyme A which enters the Krebs cycle - Coenzyme A is derived from vitamin B - It behaves as a carrier/taxi for the 2C acetyl group Krebs cycle - The Krebs cycle is also called the citric acid cycle or the tricarboxylic acid cycle - It's a series of biochemical reactions that occur in the matrix of mitochondria - Acetyl CoA (2C) enters the cycle and combines with a 4C compound to form citric acid - The 2C component of acetyl CoA is pulled apart bit by bit to release CO2 and H+ - The H+ are sent to the electron transport chain (ETC) as NADH2 and FADH2 to be converted into energy to be converted into ATP - Potential energy in the chemical bonds is released step by step to reduce the coenzymes (NAD+ -\> NADH2; FAD+ -\> FADH2) which temporarily store this energy - NAD+ and FAD+ are the H2 carriers - 2C Acetyl CoA + (4C) oxalo-acetic acid -\> 6C (citric acid) - The series of reactions incolving the removal of 2C and 4O as (in the form of) 2CO2 and the removal of hydrogen occurs - 6C citric acid becomes 4C oxalo-acetic acid to complete the clinic pathway - Summery - Each acetyl CoA molecule that enters the krebs cycle produces - 2 molecules of CO2 - 3 molecules of NADH2 - 1 molecule of ATP - 1 molecule of FADH2 - Each glucose produced 2 acetyl CoA molecules - Total yield = above products x 2 Electron transport chain - The electron transport chain is located in the mitochondria - Integral membrane proteins (cytochromes) form a chain which is located in the inner mitochondrial membrane - Each cytochrome picks up electrons and passes them to the next in the chain - Small amounts of energy are released as this occurs - This energy is used to form ATP - Oxidative phosphorylation produces the vast majority of ATP in the cell - The electron transport chain is a series of chromosomes located in the inner membrane of the mitochondria - Hydrogens delivered to the chain are split into proteins (H+) and electrons - As electrons are passed through the chain there is a stepwise release of energy from the electrons for the generation of ATP - H+ ions are transported from the matrix into the space between the inner and outer membranes - This ensures a high concentration of H+ is established between the inner and outer membranes - ATP is formed as H+ diffuses through the special ATP synthase channels back into the matrix Steps in the electron transport chain - Proteins of the ETC are clustered into 3 complexes that each act as proton pumps (move H+ into the inner membrane space) - The electrons are shuttled from one cytochrome to the next - The final complex passes its electrons (2H+) to half of O2 molecules to form water (H2O) - The build up of H+ outside the inner membrane creates a positive charge - Electrochemical gradient of potential energy - ATP Synthase enzyme within H+ channel uses this potential energy from ATP from ADP and iP Summery of aerobic cellular respiration - Glucose (+O2) is broken down into CO2 + H2O + energy (ATP): - 2 ATP's are formed during glycolysis - 2 NADH2 are formed during glycolysis - 2 NADH2 are formed when converting pyruvate to acetyl CoA - 2 ATP's are formed directly during krebs cycle - 6NADH2 are formed during krebs cycle - 2FADH2 are formed during krebs cycle - For each NADH2 the proton gradient generates 3 ATP - 10NADH2 generates 10x3 ATP = 30ATP - For each FADH2 the proton gradient generates 2 ATP - 2FADH2 generates 2x2 ATP = 4ATP - From each glucose molecule 4 ATP are created - Oxidative phosphorylation generates 36-38 ATPs from one glucose molecule - \*2 x NADH2 formed during glycolysis produce less ATP via OP - The complete oxidisation of glucose can be represented as follows - Benefit: H2 obtained from a wide variety of organic molecules, they can be funneled through this process to form a common energy carrier -- ATP - Involves a complex series of reactions in the mitochondrion - Oxidative phosphorylation produces the vast majority of ATP in the cell Cellular respiration - Metabolic pathways synthesise ATP - Anerobic: ATP production in absence of O2: glycolysis - Small amounts of ATP - Aerobic: ATP production using O2: oxidative phosphorylation - Fuel + O2 -\> co2 +h2o + energy - Large amounts of ATP Tutorial Experiment Solution C ----- ------ ------- ------ --------------- ----------- "0" 50ml "3.5" 50ml Took up water No change ----- ------ ------- ------ --------------- ----------- A Increased Decreased Bag to cylender Hyper tonic \>290 --- ----------- ----------- ----------------- ------------- ------- B No change No change Equal Isotonic =290 C Decreased Increase Cylinder to bag Hypotonic \