BMB 462 Lecture 6 Outline of Last Lecture I Selectively permeable membranes II Membrane Energetics a Activation barrier b Electrochemical potential c Passive and Active transport III Means of Classifying Membrane Transporters a Energetics b Transport Properties c Solute and Direction of Movement IV GLUT family transporters V Primary Active Transport Outline of Current Lecture I Continuation of Primary Active Transport a P Type Continued b F Type and V Type ATPase c ABC Transporters II Secondary Active Transport a Lactose Permease b Na Glucose Symporter III Signal Transduction a General Features b General Process c Types of Receptors d Example Beta Adrenergic Receptor Current Lecture Concepts 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 Transport a P Type Continued i 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 bind 2 ATP binds and phosphorylates P EnzII to cause a conformational change opening the transporter on the outside of the membrane 3 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 transporter 5 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 gradient ii 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 transport b F Type and V Type ATPase i 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 gradient 1 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 gradient ii Know the structure A channel of beta barrels and alpha helices creating a crank that gets phosphorylated to move protons through c ABC Transporters aka ATP Binding Cassette i Structure 2 nucleotide binding domains and 2 sets of transmembrane helices 6 10 helices per set ii Function Primary active transport with conformational change 1 Flopases move lipids across membranes to control lipids in the leaflets 2 They also act as channels though the mechanism is not well understood a ATP binding hydrolysis acts as a switch to open close the channel b Cystic Fibrosis occurs in an error in an ABC Transporter that is used as a channel iii ABC transporters are multidrug resistant transporters 1 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 effective II Secondary Active Transport a First solute moves along the gradient to create an electropotential gradient to move the second solute against its gradient b Lactose Permease i Function Moving lactose into the cell Lactose has a positive G so it needs the aid of a proton gradient to move in The proton moving into the cell has a negative G favourable ii Energy Source Proton gradient iii Classification Major Facilitator Superfamily symporter secondary active transporter c Na Glucose Symporter i Function To move glucose from intestines the digestive system into the cells ii 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 Transduction a Cells need to be able to sense environment and respond by changing cell interior b General Features i 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 reaction ii Sensitivity 1 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 enzyme a This continues until you have up to thousands of active enzymes b i e Phosphorylation cascade results in many active enzymes to amplify signals iii Desensitization This allows the system to function across a wide range of input 1 The receptor is no longer as sensitive as it was 2 The signal comes in to create a negative feedback loop iv Integration When there are 2 different signals that cause opposite effects 1 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 the signals a i e insulin and glucagon which bind to different receptors insulin indicates high blood sugar and glucagon indicates low blood sugar c General Process i Signal the 1st messenger i e a hormone light heat voltage change 1 The signal starts the whole process ii Receptor a protein that senses the change it binds to hormone feels the heat etc and causes a conformational change 1 i e a neuron feels voltage and opens to let ions cross 2 i e Insulin binding to its receptor iii Signal transduction 1 2nd Messenger s small diffusible signals that regulate other components a i e IP3 or DAG cyclic AMP GMP Ca2 2 Phosphorylation Cascades another way to amplify a signal response a Enzyme 1 is phosphorylated and then phosphorylates enzyme 2 which then phosphorylates enzyme 3 i Phosphorylation activates an enzyme iv Cellular targets 2 categories 1 Regulated Enzymes in Pathways is caused by phosphorylating enzyme to change activity 2 Transcription Factors cause a change in gene expression v Cellular Response the cell experiences changes in enzyme activity membrane potential gene expression etc vi Signal Termination signals need to be transient cells need to be able to turn off the signal 1 i e with desensitization signal degradation by enzymes that break down hormones degradation
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