2 2 15 Lecture 9 Receptor Characteristics Activation ligand binds o Based on shape and charge Specificity limited binding o We never talk about affinity unless we have specificity Affinity strength of binding o High affinity reactants get consumed faster Saturation activated o Describes the number of receptors bound in an area o Figure 5 3 o Food analogy If you a party the food that has a high affinity would have a high saturation Competition o Figure 5 2 o A second ligand that also has specificity for the same receptor Binds to the protein o 2 options that can happen as a result Antagonist no response It triggers a shape change but not the correct shape change that we need Always have specificity for the receptor and usually do not create the same response as the natural ligand It has no effect because it is blocking the receptor We get the shape change we need A lot of drugs are agonist Can cause the same effects either stronger or weaker or same Agonist response Signal Transduction Pathway Activation converts signals into response o The signal is the ligand binding and the transduction is the series of events or processes that the cells undergoes to get the response o That response is a change in the physiology o Enzymes always cause and amplification Amplification Amplification one messenger ligand can produce many actions we make more of what was there before The binding of one ligand can activate an enzyme that will continue to do actions as long as that ligand is bound to the receptor So it does not take many ligand to produce a large response o Possible responses Change in membrane permeability A protein channel is opened or closed 2 2 15 Analogy to being home alone and you parents say nobody can come over except you aunt you are changing what can enter Alter Metabolism Work off of Krebs cycle if glucose is low Used anaerobic We can change what our starting products are o If the enzyme is one of the enzymes used in Change contractile activity metabolism Shape of cell changes Could be circular flat thing etc o Like if you stimulate the muscle cells Secret product Secret one endocrine and releases other ones as a result Send out a messenger Change in proliferation or differentiation rate Either makes more of the same cell or differentiates a cell that is undifferentiated Location types o Location determines the type of receptor o 1 Intracellular within cytosol or nucleus Ligands can bind to a protein inside the cell o 2 Membrane bound Sitting in the surface of the cell Intracellular receptors Within nucleus or cytosol either way it is inside the plasma membrane End up being promoters of DNA o These ligands are transcription factors that bind to and change the shape of the promoter Our ligands need to be able to cross the plasma membrane to get to receptor o So the ligand must be small and nonpolar o Figure 5 4 o This is an endocrine because it traveled through the plasma The plasma is water based and the ligand is nonpolar oh no Intracellular ligand can come from plasma Intracellular just means that is binds to something in the intracellular space Ligand nonpolar and plasma polar sooo Ligand needs a plasma binding protein o The plasma binding protein is amphipathic Creates a nonpolar pockets for the ligand to sit in while in plasma The plasma binding protein stays in the plasma The ligand can also bind in the cytoplasm not just the nucleus Complex in Nucleus o The complex either moves in or is already in the nucleus o Ligand bound to receptor in the nucleus 2 2 15 o This complex interacts with the DNA o The complex can be formed in the cytosol but must end up in the nucleus Result always alters DNA use o When an intracellular receptor is activated we will ALWAYS see a change in how the DNA is used o It will either activate or suppress gene expression by altering the rate at which proteins are made Membrane Bound Receptors Ligand polar no entry into cell o Only 1st in relay 2nd o 2 means that we can have more than one interaction occurring in order to get a response In other words one ligand can create multiple responses o Think if it like a relay race when a ligand binds the polar ligand will only be the first runner of the relay race o After the ligand has bound to a membrane bound receptor another interaction can be triggered Note We can also classify the types of receptors based on their polarity too not just their location Do all membrane bound receptors cause multiple responses Four categories of membrane bound receptors o 1 Functions as ion channel Bind of ligand changes channel from being closed to open Figure 5 5 Must be a ligand gated ion channel Result Just changes the electrical gradient membrane potential Ions moves so there is a change in the charge distribution o 2 Functions as an Enzyme Tyrosine Kinase Kinase enzyme that does equation number 1 breaks down ATP to release energy Uses ATP to phosphorylates things directly Binding a ligand activates its enzymatic activity Figure 5 5 Result cascade of phosphorylations The P is moved on to various different proteins That one P that came off from one ATP and is used on various different proteins Analogy to have a 20 and using a little bit at a time to buy o 3 Interact with JAK kinase food for a lot of meal The second protein within a path The receptor that activates the JAK kinase is the middle man A ligand binds to the transmembrane receptor and activates The activated receptor then activates the JAK kinase Shape change in one protein causes a shape change in the second protein that s associated with it it 2 2 15 o 4 Interact with G protein G protein subunits Analogy to couple holding hands one falls so does the Results in shape changes result from the binding of a other phosphate The JAK kinase will then phosphorylate a protein by removing a P A receptor is a proteins so we could also say it makes more from ATP Result synthesis of new proteins receptors NEED TO KNOW WHAT A KINASE IS They break down ATP made up of 3 different subunits alpha beta gamma We say that it is heterotrimeric The G protein is the 2nd protein kind of like the JAK is The G protein interacts with a 3rd protein the PMEP and that one causes a reaction G proteins also phosphorylates but it is not direct it is indirect because it goes through a cascade of events This is the most complex and also the most common in our body So we need to learn the details about this Alpha subunit has GTP Alpha subunit separates off GTP doesn t break down until it
View Full Document
Unlocking...