BMB 462 Lecture 6 Outline of Last 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 TransportOutline of Current Lecture I. Continuation of Primary Active Transporta. P-Type Continuedb. F-Type and V-Type ATPasec. ABC TransportersII. Secondary Active Transporta. Lactose Permeaseb. Na+/Glucose SymporterIII. Signal Transductiona. General Featuresb. General Processc. Types of Receptorsd. Example: Beta- Adrenergic ReceptorCurrent LectureConcepts to remembers from previous courses/lectures:- The role of ATP synthase in mitochondria and chloroplasts-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.I. Continuation of Primary Active Transporta. P-Type Continuedi. Example: The Na+/K+ ATPase (Antiporter: Na+ and K+ move in opposite directions across the membrane.1. The Transporter starts open to the inside of the cell, for Na+ to bind. 3 Na+ bind2. ATP binds and phosphorylates P-EnzII to cause a conformational change, opening the transporter on the outside of the membrane3. The 3 Na+ are released outside of the cell and 2 K+ from outside are bound.4. K+ binding causes the Pi to be released, which leads to another conformational change, resetting the transporter5. Moving 3 Na+ out and 2 K+ in means that 3 positive charged molecules are removed from the cell and only 2 are brought back in, creating a charge gradientii. Membrane potential created from ion transporter (i.e. with Na+/K+ ATPase) is the basis for action potential. A gradient is created for many secondary active transports 1. i.e. Na+ wants to move back into the cell along its gradient, after being removed by the ATPase, and this movement creates energy potential for other transportb. F-Type and V-Type ATPasei. ATP synthase usually has protons flowing down their gradient to catalyze ATP. In F-type and V-type hydrolize ATP to move protons against their gradient1. They function in 1 direction in mitochondria and chloroplasts to synthesize ATP. In other areas of the cell, they move in the other direction to move protons with ATP energy to create a gradientii. Know the structure! A channel of beta-barrels and alpha-helices creating a crank that gets phosphorylated to move protons throughc. ABC Transporters; aka ATP Binding Cassettei. Structure: 2 nucleotide binding domains and 2 sets of transmembrane helices (6-10 helices per set)ii. Function: Primary active transport, with conformational change1. Flopases move lipids across membranes to control lipids in the leaflets2. They also act as channels (though the mechanism is not well understood)a. ATP binding hydrolysis acts as a switch to open/close the channelb. Cystic Fibrosis occurs in an error in an ABC Transporter thatis used as a channeliii. ABC transporters are multidrug resistant transporters1. i.e. Cancer cells become resistant to chemotherapy because they start expressing ABC transporters that move chemo drugs back out of the cancerous cells, where they are no longer effectiveII. Secondary Active Transporta. First solute moves along the gradient to create an electropotential gradient to move the second solute against its gradient.b. Lactose Permeasei. Function: Moving lactose into the cell. Lactose has a positive ΔG, so it needs the aid of a proton gradient to move in. The proton moving into thecell has a negative ΔG (favourable)ii. Energy Source: Proton gradientiii. Classification: Major Facilitator Superfamily, symporter, secondary active transporterc. Na+/Glucose Symporteri. Function: To move glucose from intestines (the digestive system) into the cellsii. Energy Source: Na+ gradient (the Na+/K+ ATPase keep Na+ concentration low in the cell to create a gradient for the Symporter)iii. Classification: Secondary active transporter, symporter- Beginning of unit on Signal Transduction - III. Signal Transductiona. Cells need to be able to sense environment and respond by changing cell interiorb. General Featuresi. Specificity: very specific; with a Kd of 10-10, cells bind very tightly to the signal.1. High affinity also means high sensitivity; receptors don’t need as much of the signal solute to bind to cause a reactionii. Sensitivity1. Cooperative Binding: 1st molecule binds to receptor and increases affinity of the receptor to the second molecule (resulting in increased sensitivity)2. Amplification: 1 signal activates an enzyme; the enzyme produces 3 products each of which activate another enzymea. This continues until you have up to thousands of active enzymesb. i.e. Phosphorylation cascade results in many active enzymes to amplify signalsiii. Desensitization: This allows the system to function across a wide range of input1. The receptor is no longer as sensitive as it was2. The signal comes in to create a negative feedback loopiv. Integration: When there are 2 different signals that cause opposite effects1. The cell can integrate across both of those signals (it doesn’t just turn on or off; the amount of signaling depends on the ratio of thesignalsa. i.e. insulin and glucagon, which bind to different receptors (insulin indicates high blood sugar and glucagon indicates low blood sugar)c. General Processi. Signal (the 1st messenger) – i.e. a hormone, light, heat, voltage change,1. The signal starts the whole processii. Receptor – a protein that senses the change (it binds to hormone, feels the heat, etc) and causes a conformational change1. i.e. a neuron feels voltage and opens to let ions cross2. i.e. Insulin binding to its receptoriii. Signal transduction1. 2nd Messenger(s) – small diffusible signals that regulate other componentsa. i.e. IP3 or DAG, cyclic AMP/GMP, Ca2+2. Phosphorylation Cascades – another way to amplify a signal responsea. Enzyme 1 is phosphorylated and then phosphorylates enzyme 2, which then phosphorylates enzyme 3i. Phosphorylation activates an enzymeiv. Cellular targets (2 categories)1. Regulated Enzymes in Pathways - is caused by phosphorylating enzyme to change activity2. Transcription Factors – cause a change in gene expressionv. Cellular Response – the cell experiences changes in enzyme activity, membrane potential, gene expression, etcvi. Signal Termination – signals
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