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MSU BMB 462 - Membrane Energetics and Transporter Classification
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BMB 462 1st Edition Lecture 5 Outline of Last Lecture I. Review of Hydropathy PlotsII. Fluid Mosaic Modela. Additional proteinsb. Membrane dynamicsIII. Membrane FusionOutline of Current Lecture I. Selectively-permeable membranesII. Membrane Energeticsa. Activation barrierb. Electrochemical potentialc. Passive and Active transportIII. Means of Classifying Membrane Transportersa. Energeticsb. Transport Propertiesc. Solute # and Direction of MovementIV. GLUT family transportersV. Primary Active TransportCurrent Lecture- Beginning of the unit on Membrane Transport - Concepts to remembers from previous courses/lectures:- Entropy; ΔG, ΔG’°, ΔGdouble dagger- Concentration Gradients and electrochemical gradients- Half saturations: km and kt- Read in the book: Structure and classification of protein transporters, so that you know mechanismI. Selectively-permeable membranes: some molecules can cross the membrane, with or without aid, and others cannot.a. Small hydrophobic molecules can go across the membrane unaidedb. Need proteins in the membrane to get other molecules across.i. The type of protein determines what type of molecule can cross These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.c. Different cells in different tissues will have different transporters depending on what molecules are neededd. There are probably over 1000 membrane transporters in the human genome; about 4-5% of proteins in the genome are for transportersi. Aka it’s really important for cells to move molecules across membranes in the right waye. Complications with membrane transport:i. An ABC transporter that moves chloride across lung epithelial (from the cells into the airways). This movement also helps move water into the lungs and the extra water loosens mucus in the airways1. Absence or mutations with this transporter cause Cystic Fibrosis; mucus in the airways thickens and results in many bacterial infections. Individuals with C.F. typically die by age 30 from complications.II. Membrane Energeticsa. Important coefficients and variablesi. Vmax is the maximum saturation of a solute the transporter can supportii. Kt is analogous to Km, which equals the concentration at which a transporter is half saturatediii. ΔGdouble dagger is a transporter’s activation energy and determines the rate oftransport; ΔG’° is standard conditions (at 1 mol of everything) at equilibrium so there is no net movement of solutes across the membrane; ΔG is transport at cellular conditions.b. Activation barrieri. Activation energy determines the rate at which molecules moveii. Transporters lower activation energy to make movement of molecules more favourable1. i.e. moving polar molecules directly across the membrane is thermodynamically unfavourable, but if you get a polar channel in the membrane, it is much more favourable to move the moleculesa. The rate of transfer increasesc. Electrochemical potentiali. When moving molecules without charge, only concentration matters for transportii. In charged molecules, concentration and electropotential are import1. Solutes naturally move from high concentration to low concentration2. Ions move to the opposite charge (i.e. a positively charged molecule moves towards a negative charge)d. Passive and Active transporti. If ΔG is favourable (negative) in a direction, the molecule will move in thatdirection using passive transport 1. No energy is requiredii. A cell uses active transport for unfavourable movement1. The molecule moves against the gradient and needs aid from either a direct or indirect use of ATP energyIII. Means of Classifying Membrane Transportersa. 2 examples of classification methods include whether the transporter uses active or passive diffusion, and based on structurei. A structure-classified family of transporters are the Major Facilitator Superfamily (MFS) transporters1. They can do passive, active, anti-/symport, and uniport transportation – they have many functions2. But structurally, all have 12-14 transmembrane alpha-helicesb. Energetics (read more details on these transporters in the book)i. Passive diffusion – No energy input is required, solutes move down the gradient1. Simple diffusion – does not require a transporter, the solutes can diffuse directly through the membrane. Not many molecules transport through simple diffusion2. Facilitated diffusion – Involves a protein transporter3. Ion Channels – offer a polar environment for charged molecules tomove through. Because the channel is open, it doesn’t require energy to move molecules through4. Ionophores – small molecules that bind to ions and move the ions across the membrane (note: we won’t focus on these in BMB462)ii. Active transport – This requires energy and is used to move molecules against their gradient1. Primary transport – uses energy directly from ATP (creating ADP + Pi)a. The 3 types of primary transport include P-type, F-type, and ABC transporters2. Secondary transport – 2 solutes move through the transporta. 1 solute moves with its gradient, at a – ΔG, which causes the release of free energyb. The release of free energy causes a second solute to move against gradientc. Frequently, primary active transport creates the gradient needed for secondary transportc. Transport Propertiesi. Channels (i.e. ion channels) – form pores in the membrane that can open or close. When opened, transport reaches the approximate rate of unhindered diffusion1. Channels are not very stereospecific, and do not interact with every molecule that passes throughii. Carriers – have enzyme-like kinetics; they saturate well below the rate of diffusion1. Carriers are very stereospecific and interact with every molecule2. They open on 1 side of the membrane, a molecule binds, conformational change of the protein occurs, and the carrier now opens on the other side of the membrane, where the molecule is releasedd. Solute # and Direction of Movementi. Uniport – 1 solute molecule moves through the transport at a timeii. Cotransport – 2 molecules move through the transporter1. Symport – Solutes 1 and 2 move in the same direction across the membrane2. Antiport – Solute 1 moves in the opposite direction of solute 2IV. GLUT family transportersa. Function: Move glucose (and sometimes other types of sugar), are very stereospecific so they can only move D-isomer sugars, not L-isomersb.


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MSU BMB 462 - Membrane Energetics and Transporter Classification

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