not away from today but if today we’re Friday it would be a week from today all right so I’ve got a fair amount of material to cover a little bit behind but not a problem last time I get started talking about the signaling through the beta adrenergic receptor which is shown right here and we saw how that a signal comes from outside the cell can cause some big changes inside the cell and I talked about how protein kinase a becomes activated I haven’t yet talked about what protein kinase a does alright so that will come later but suffice it to say that protein kinase a’s action as far as this class is concerned will be activating some enzymes that are involved in breaking down glycogen which is how the cell is making or the body is making glucose available in the bloodstream so we’ll talk more about that when I talk about glycogen metabolism we’re all this stuff will hopefully start coming together okay there’s a G protein memorize that structure and write it for the exam the G protein has three subunits as I mentioned last time it has an alpha subunit it has a beta subunit and a gamma subunit and the beta and gamma bind to the Alpha as you see as shown here schematically and they in doing so cover up a binding site for the identity cyclase and so it’s the combination of the loading of the GTP and the release of the beta and gamma subunits that allow the alpha subunit bound to GTP to connect to the adenylate cyclase in favor the synthesis of cyclic am P okay as I mentioned last time the g proteins are bad enzymes and their bad enzymes in the bad in the sense that they’re inefficient and their inefficiency helps them to turn themselves off and as we’ll see later today the inability to turn themselves off at times can cause some major problems so that’s important to keep in mind the overall epinephrine signaling pathway looks like this in words compared to what you saw in the schematic diagram so I don’t care how you learn that one way of learning I find the figure is a little more helpful but you notice that there’s several levels of amplification and these amplifications happen through the synthesis of molecules or the activation of enzymes so that at each level we get an increase in the amount of signal and this increase in the amount of signal is what we saw in the cascade for example for the blood clotting proteins and that signaling cascade allows a very small signal to be amplified very much and very rapidly and so this is why adrenaline acts fairly quickly the major limitation in the action of adrenaline is not the action that occurs inside the cell it’s actually the getting it to the cell because adrenaline has to travel through the bloodstream okay resetting g-proteins is important and that’s related to their what I’ve described is their inefficient enzymatic action you can see here GTP bound to a dental a cyclase over time that enzyme will in fact cleave that GTP to create an alpha subunit that has gdp bound to it that gdp subunit will be less gdp-bound subunit will be less inclined to bind to a dentally cyclase and will later to link up back up with the beta and gamma and go back to the original state that we talked about before where it’ll be adjacent to the beta adrenergic receptor okay now single termination is pretty important right so you saw last time I talked about the importance of phosphodiesterase because phosphodiesterase is present in cells at a low level and so over time it breaks down cyclic a.m. piece so if cyclic GMP gets built large amounts over time the phosphodiesterase will take over and start breaking that down well that’s only going to work if the identity Cyclades stops making the cyclicamp eat and that means that the very beginnings of this signal also have to have some controls so cells have a sort of a backup mechanism of ensuring that the binding of the hormone to the receptor on the cell surface originally making sure that that binding actually does get turned off and so this is a what I’m showing you on the screen is a sort of a backup mechanism of turning off that signal that’s coming from the beta adrenergic

receptor you can see in the scheme of things that a receptor lacking a epinephrine can bind to one and getting put into an activated state that’s you’ve already seen before you can also see that the release of that epinephrine can occur as you see here by the process described as dissociation but if dissociation doesn’t happen well let’s say this hormone gets stuck in here and this receptor got stuck in the on state that would be problematic for the cell because it would be continually stimulating the cell to make cyclic GMP to activate protein kinase to continue to produce glucose and that would cause the cell ultimately to die because it couldn’t do that forever so one of the ways of ensuring that that doesn’t get stuck in that on mode is the process that you see on the screen and this is through the action of something called a receptor kinase receptor kinase can recognize that this beta adrenergic receptor is stuck in the on state and if it detects that what it will do is it will phosphorylate a couple of sites on the inside of the cell there that’s the outside above and the inside below it will phosphorylate a couple of sites on that beta adrenergic receptor putting phosphates onto some amino acids in the adrenergic receptor and those phosphorylated sites become the target for this protein called beta arrestin and when bata arrests and binds to this complex it basically stops it from interacting with g-proteins so that that signal is stopped dead in its tracks so beta-arrestin has a very simple name its arresting the process and it’s very easy to recognize for that for that purpose okay so this is yet another way of turning off that signal so you can see that cells really place a lot of importance on turning on and turning off the signals another mechanism that is a signaling mechanism that’s found inside of cells involves activation of another enzyme and this also works through a 7tm I don’t have a figure showing you this 70 m but this 70 M ultimately activates an enzyme called phospholipase seen I’m talking about a different signaling mechanism here this signaling mechanism may play roles in constriction of blood vessels for example and there’s a variety of ways in which it can act but the bottom line of this signaling pathway is that the activation of this pathway activates an enzyme on the inside of the cell called phospholipase C phospholipase C catalyzes the reaction that you see on the screen and this reaction should see on the screen is interesting and important ok so if we look at the substrate for phospholipase C if this model of this molecule appear in phosphatidyl inositol 4-5 bisphosphate blah blah blah you can call it pip – pip – is a very common molecule that we find inside of cell membranes very common molecule found inside of so many so this is very abundant inside of cells and when phospholipase c is activated it breaks the bond between this congas compound up here shown in red which is ip3 to give it a short name and the remaining portion which is die so glycerol or da G all right now it’s important here because these both of these molecules act in a signaling capacity they both act as second messengers so this signaling pathway that I’m describing to you here involves creation of two second messengers and it happens through the activation of phospholipase C now what happens in this process is that you see the breaking of the bond between these two things here the ip3 is as you can see by its chemical structure very polar it’s very water-soluble and it’s very much able to travel in the cytoplasm remember this guy is found in the membrane so this whole complex up here is starting in the membrane cleaving of the compound by phospholipase C releases ip3 which now can travel in the cytoplasm okay what’s left behind in the membrane is this molecule called da so

glycerol or da G as they said both of these compounds will act in this this mechanism I’m going to describe to you has second messengers okay so one left in the membrane one travels in the cytosol all right this depicts schematically what I just described to you all right here’s the membrane here’s the PIP – that you can see in the membrane with the attached inositol compounds activation of phospholipase c causes this ip3 to be released into the cytoplasm okay the release of ip3 into the cytoplasm causes ip3 to freely go to the endoplasmic reticulum and at the endoplasmic reticulum there is a receptor that binds to ip3 so we see a receptor we see a receptor and now ip3 is causing endoplasmic reticulum to open up its gates and when it opens up its gates one of the things that’s stored in the endoplasmic reticulum is calcium what’s happening here is this signaling mechanism is causing the calcium concentration inside the cytoplasm causing the enterprise cosmic the calcium concentration inside the cytoplasm to increase i’ve told you previously that calcium was kind of a critical eye on inside of cells cells manage the levels of calcium because too much calcium causes DNA to precipitate so that means that the calcium concentration inside the cytoplasm starts out pretty low starts out pretty low the cells are pumping calcium into the endoplasmic reticulum to keep the cytoplasmic concentration low so when this signaling process comes along it opens up the endoplasmic reticulum calcium concentrations rise calcium concentrations rise make the calcium can bind to another kinase called protein kinase c and of protein kinase is here protein kinase c is located at the membrane and it’s bound to the other second messenger Dino so glycerol we can kind of think of calcium here as a third messenger because it was released upon the release of the second messenger which is ip3 okay what is happening here is the binding of protein kinase C by both diacylglycerol and calcium causes protein kinase C to become activated and activation of protein kinase C can cause many things to happen in the cell including gene expression specific gene expression so here’s another signaling mechanism this signaling mechanism isn’t quite as targeted as the one I described to you before for the beta adrenergic receptor but we can see activation of a protein kinase and that protein kinase can cause many things to happen in the cell again a lot of things happening as a result of binding of a hormone to the cells service okay so signaling mechanisms as you can see our multi-step they involve messengers and those messengers travel through the cell in order to make things happen a very common occurrence of signaling is activation of a kinase and we don’t go through them in this class I’ll show you an example later but we’ll see that kinase can activate kinase can activate kinase can activate kinase as that is we can see a whole series of these again not unlike that we saw with the protease cleavage that happens in blood clotting okay that’s amplification of signal is a very important component of the signaling process okay what calcium is important and calcium is also something that I’ve told you that the cell has to be careful with the cell has to be careful with calcium because as I said too much calcium chromosomes precipitate right so when calcium is released in cells cells actually have proteins that will gobble up that calcium and allow stop the free calcium concentration from getting too high one of the proteins it’s very important in grabbing a hold of calcium there’s a protein that you see on the screen schematically shown is what was called an EF hand protein but the specific

protein is called calmodulin c al mo d u li in calmodulin is a small peptide that has a structure kind of like this these are called EF hands and right here is where the calcium will bind now the binding of calcium by a calcium binding protein not surprisingly causes the calcium binding protein to change shape causes the calcium binding protein to change shape here’s calmodulin without the calcium okay we see the binding of the calcium that causes a somewhat of a structural change and that small structural change that’s happening here on the binding of calcium facilitates a bigger structural change that allows the calmodulin to bind to another protein and activate it okay so I’m going to step you through this we’ve gone through the phospholipase C pathway we’ve released calcium in the cell the calcium has bound to a protein called calmodulin caused a small structural change in calmodulin that structural change was enhanced by another enzyme and that binding of the other enzyme by calmodulin activated it the consequence here is that calcium is activating another protein just like cyclic AMP II was activating protein kinase a calcium is activating indirectly through the binding of calmodulin another enzyme now the beauty here is again a protein is binding calcium that leaves the free calcium concentration relatively low yet still a signal is being propagated as a result of the calmodulin x’ a change in shape that’s happening questions on that yes over here is the calmodulin activated the protein activated so when we talk about activation it’s all a relative thing calmodulin has changed you can see the gaining of the shape that’s happening here in the middle compared to what it was so calmodulin has changed its shape calmodulin doesn’t catalyze a reaction though so I don’t think of calmodulin in terms of activation all right but calmodulin has definitely changed from the state that it was in and it’s activating this other enzyme as a result of that shape change make sense yes Garrett is there a reverse process to this what are you supposed okay how would we reverse this process good question yeah so as we start removing the calcium calcium there these are not covalent bindings so we have non covalent bindings these things can come back out this guy will lose its calcium and will lose its calcium it’s going to go back to this state here it’s no longer going to activate that enzyme and we reverse the process now cells have as we as you will see next term various what I call pumping mechanisms for taking calcium and pumping it back into the endoplasmic reticulum that’s important because it had to get there in the first place somehow right so those pumping mechanisms will take over in time take the calcium pump it back into the endoplasmic reticulum thereby reducing the calcium concentration in the cytoplasm and thereby reduce reversing this process okay what you see yeah question apo means no no ion bound APO means empty literally yeah okay well let’s talk about perhaps a bit more interesting kind of signaling process that happens the Sigma process I’m going to talk about now relates to insulin okay and insulin signaling does not occur through 7tm the first two I’ve described occurring through 7tm this process does not occur through a 70 M it occurs through something called the insulin receptor and the insulin that’s insulin right there the insulin receptor looks schematically like this okay it’s not a 70 M it is a transmembrane protein as all receptors are and if we look at this we see an outside the cell on the top we

see an inside the cell on the bottom insulin is an example of a receptor that’s what we call a tyrosine kinase mediated receptor tyrosine kinase mediated receptor now the kinase as I’ve talked about so far remember a kinase means put phosphate onto the kinase as I’ve talked about so far put phosphates onto Sirians and threonines they don’t put phosphates onto tyrosine but I told you when I first talked about kinase is that some kind a suspect’s onto tyrosine this is the first kinase that we’re seeing that puts phosphates onto tyrosine okay now I’m gonna step you through what happens with this process and what you’re seeing in in these signaling pathways is this goes to this goes to this goes to this goes to this okay that’s what happens in signaling I do spare you some of the details but wherever I talk about this going to this going to this going to this then yes you should know that okay okay what happens in insulin signal first of all let’s think about what’s happening with insulin in the first place remember I said last time that glucose is a poison glucose is a poison your body treats it as if it’s a poison and it that’s because it acts as if it’s a poison high levels of glucose which happen in diabetes have very detrimental effects for people can lead to blindness especially among the elderly it’s not uncommon for the high glucose levels to result in amputation of land and these high levels of glucose are the cause of the problem glucose is a poison in your bodies if you’re not diabetic what’s happening is insulin is helping to modulate the levels of glucose that you have in your bloodstream you go eat a meal your blood glucose levels start rising your body says poison it starts making insulin and insulin causes cells to take up glucose and reduce the blood glucose levels and you might say that’s an odd kind of poison it’s a poison that the cell is taking up isn’t the cell going to die and a cell is not going to die obviously because it takes that insulin and it does something to it it modifies it I’m certain that the insulin takes that glucose and it does something to it it modifies that glucose so that it’s no longer glucose again consistent with it being a poison the cell is literally detoxifying that glucose with inside of itself okay now let’s look at the signaling process that makes this all happen eat a meal drink a coke get one of those God forbidden lattes that you get all right blood glucose levels go foing pancreas says okay got a release insulin it releases insulin insulin travels in the bloodstream and goes and hits target cells that have a receptor binds to them and then causes a series of events to happen okay you’ll notice that the insulin receptor is what we call a dimer meaning it has two identical sets of proteins and each protein is multi subunit there’s the beta subunits in yellow there’s the Alpha subunits in blue and these are shown as a dimer they exist in the cell membrane as a dimer okay I told you that this receptor is a tyrosine kinase and to remind you what a tyrosine kinase does is it takes the side chains of tyrosine and it’s phosphates on them using the ATP from I’ve been using the phosphate from ATP okay now yep here we go this shows the overall process I’m going to tell you that okay here is an insulin receptor that is bound to insulin the binding of the insulin by the receptor causes one subunit of the receptor to put a phosphate onto the tyrosine of an of the other subunit this only happens when the insulin binds to the receptor if there’s no insulin the receptor the first subunit does not put phosphates on the other one they’d sit they’re sort of intertwined blocking each other’s active site but the binding of insulin cause them to change shape so that one of them has its active site open to phosphorylate the other one it doesn’t

matter which one for our purposes okay when one of the subunits puts phosphates on the Taira scenes of the other one the other one changes shape and starts putting phosphates back on the first one so they are phosphorylating each other you can see there’s multiple phosphates that get put on to there and those phosphates become the target for binding of a protein called irs-1 it sounds like it’s a tax thing doesn’t it okay IRS one recognizes this phosphorylated tyrosine okay it recognizes this phosphorylated tyrosine and binds to it this binding of the phosphate by the IRS one causes the tale of IRS one to be brought into close proximity to the kinase activity in the beta subunit that’s how these phosphates get put onto there okay that’s how these phosphates get put onto there so these are also phosphorylated tyrosines these phosphorylated tyrosines are targets for binding of this guy here called fossil and also type 3 kinase and phosphoenol so type 3 kinase is a membrane associated protein that is activated by two things one a phosphotyrosine here on IRS one and ii pip two in the membrane it takes pip two and it cleaves it i’m sure doesn’t cleave it phosphorylates i got it backwards it phosphorylates it okay and makes pip three that three means an additional phosphates didn’t put on to that molecule hip three in turn is a target for another protein kinase you guys love signaling I can tell PDK one PDK one in terms of protein kinase which now activates another kinase another kinase another kinase and ultimately what this signaling pathway does is it changes the movement of a very critical protein inside of the cell the movement okay we haven’t talked about protein movement other than in general terms so far but proteins can travel in the cell you may remember I said they had license plates that we could tell where they were supposed to go this kinase cascade that’s here changes the movement of a very important protein called glut Glu T there are several glutes in the cell glu T stands for glucose transport what this kinase pathway is doing is it’s altering the movement of glut in the cell prior to this insulin binding glutes floating around down in here after the insulin binding this whole pathway kicks in and glut gets moved to the membrane of the cell and glut you recall has a named glucose transport what’s happening is we’ve now told this cell bring in glucose the glucose transporter in the membrane starts seeing all this glucose that’s out there it starts bringing it in and what happens to the blood glucose levels they fall all right how much step you through it again so don’t firm too much okay let’s start with the bottom line the bottom line is release of glucose I’m sorry back up release of insulin stimulates a process that results in the movement of a glucose transport protein to the cell membrane that’s the big picture because that glucose transport protein is in the membrane the cell takes up glucose and if we do this on an organism wide action then glucose levels will fall because the cells are taking up glucose all right how they see the big picture the rest of this is the tails the details are binding of insulin

activates the tyrosine kinase of one of the units which phosphorylates the other which phosphorylates it back that makes these units completely active they in turn phosphorylate irs-1 which has recognized a structure on them and bound to them the phosphorylated tyrosine on irs-1 is a target for phosphoenol so type 3 kinase phospho knows that 3 kinase is activated makes pip 3 tip 3 is bound by PD k1 PD k1 stimulates the kinase cascade yes question about whether diabetes is a result of a problem of the insulin receptor or insulin itself the problem diabetes is actually quite complicated there’s different kinds of diabetes type 1 diabetes involves inability to make insulin and if you could imagine the inability to make insulin means blood glucose numbers gonna go whoa and you’re putting a lot of poison in the blood stream causes a real problem type 1 diabetes is not the most common type of diabetes type 2 diabetes is much more common in type 2 diabetes manifests itself in several ways people have type 2 diabetes make insulin but their body doesn’t respond to it appropriately they become what we call insulin resistant so even though the body is making insulin this process that I described to you here doesn’t occur as efficiently until a ton of insulin is made okay and so that means blood glucose levels will go very high if your body’s not responding and then all of a sudden when you get to a high enough level the body starts taking in glucose and what happens is it goes very low so people who have type 2 diabetes may have very high blood glucose levels and very low blood glucose levels hyperglycemia and hypoglycemia some people with type with hypoglycemia type 2 diabetes may have to take around a sugary drink or something with them in case their blood glucose levels fall too low because they can faint and was consciousness as a result of that that answer your question yeah question okay so how do you treat Type 2 there’s no one answer that question because there’s no one type two diabetes all right insulin is one way of dealing with that because again levels of insulin do have factors here and you can boost that by taking that more commonly to try to manage it with diet so you’ve really got to be careful with diet and that’s a very big consideration yes pip2 is acting with IRS that you’re right as well I didn’t mention that yes sir say it again can it bind to multiple phosphates here you can have multiple as long as you’ve got the appropriate phosphates exposed they can bind there yes up top yep okay so the question is is the uptake of glucose passive transport or active transport it depends on the type of cell actually blood cells have the Luntz for example that can allow passive transport to occur and other cells may require active transports so it’s not not one one straight answer question somewhere yes Stephanie yeah our question it’s actually a good question I sort of described this glut as if it’s floating around the cytoplasm that’s not really accurate the glut protein is contained typically within the under plasmic reticulum and so we’re talking about a movement you know you know how I showed the other day the movement of things from the endoplasmic reticulum to Golgi apparatus to the membrane for example that will facilitate that movement much more readily so it’s not it’s not fundamentally changing the hydrophobicity or the hydrophilicity of the protein which was what her question was yeah good question okay so insulin signaling is interesting important one term I didn’t give you and I should give you I want to make sure is that this this domain of a protein that recognizes possible tyrosine has a name it’s called an S r2 domain that’s r2 domain that’s a specific structure that’s found in many proteins and that specific structure recognizes phospho tyrosine phosphotyrosine as we shall see is very important in many signaling mechanisms that affect cells choices to

divide or not to divide what I’m showing you here with the insulin receptor I should point out is only one of a zillion things that the insulin receptor can affect insulin receptors are implicated in processes that include cancer cell division and a variety of things so insulin receptor is a very very important and multifunctional receptor insulin in many ways is there because glucose is a poison and insulin itself the more we produce insulin may be also indicative of other problems so we want to if we think about things relative to high carb diets low carb diets okay maintaining low carb diets allows us to keep our insulin levels at a relatively low level and there probably are some very good reasons to do that as well so there is some truth to the fact that maintaining low carb levels probably are good getting crazy with that no but monitoring your your carbohydrate levels is good here’s the sh2 domain that i mentioned briefly and it is a specific structure in a protein that recognizes phospho tyrosine as I said before you can see there are some arginines that are involved in that recognition and they interact with the negatively charged phosphate on the phosphotyrosine okay well pass on that there is the words of what I just told you the next thing we mechanism I want to talk about relates more directly to cell division and this one you’ll start to see again how these kinases play roles and the overall regulation of it of a cell okay the system I want to talk about here is called the epidermal growth factor system okay so the epidemic growth factor is a hormone it is a hormone that can stimulate cells to divide it can stimulate cells to divide and it works by binding to a receptor in the membrane of cells you’ve heard this before and the receptor that it binds to has the very confusing name of epidermal growth factor receptor okay that’s a joke alright so epidermal growth factor binds to epidermal growth factor receptor the receptor is shown here and if you look at that you say boy that sure kind of looks like that insulin receptor and from a schematic point of view it does there is a big difference though one of the big differences with the epidermal growth factor receptor is it does not normally exists as a dimer in the membrane it exists as a monomer you see it as a dimer here because this receptor has bound to epidermal growth factor and when one epidermal growth factor binds to a website when one receptor for epidermal growth factor binds to epinet can’t sit when what EGF receptor binds to EGF its shape changes slightly the shape change involves this little red thing right here the red thing has totally folded up inside the cell but when an EGF receptor binds to EGF this red thing serves sticks its hand out well it takes another receptor binding to EGF to stick its hand out and the two hands interlocked that’s how the dimer forms if there’s no EGF bound to the EGF receptor the hands are closed inside themselves and these receptors just float through the membrane as monomers so it’s the binding of the EGF by the EGF receptor that causes the monomers sixth in their hands and dimerize a bit clearer on that the binding of the receptor causes the dimerization that’s different from insulin insulin the receptor was already a dimer what you’re going to like this mechanism because the dimerization of this receptor causes a series of events to happen very much like what happened with the insulin receptor the EGF receptor is also a tyrosine kinase the tyrosine kinase phosphorylates each other causes each one to become more active the phosphorylated tyrosine of the receptor is a target for this protein called curb to curb to has an S r2 domain recognized as possible tyrosine binds to it another

protein called SOS binds to group two only after it has bound to phosphotyrosine so the series of events EGF receptor dimerizes as a result of each unit binding EGF the dimerize receptor causes protein kinase in protein kinase to become active so the tyrosine on each receptor become phosphorylated those phosphotyrosine are target’s for binding by herb 2 which has an S r2 domain herb 2 bound to this is a target for binding by SOS help and now we get to the meat of this SOS is target for binding a really interesting protein called rest rest Ras now wrasse turns out to be a fascinating protein our cells have several different forms of rass but each of those forms of rass are involved in activating or helping the cell to make the decision do I divide or not divide okay so this process here is important if this signal makes it all the way through grass becomes activated and I’ll explain that in a minute and the activated form of grass is a signal to the cell they’re telling us to divide let’s divide okay so we can imagine you’re a growing individual you need to make new bone cells for example your body says hey work we need to grow starts releasing growth hormone growth hormone comes activates process bone cells start dividing and you start growing okay that’s if everything’s working fine and dandy we can imagine that we can screw this process up if we screw this process up and we activate Rass and we really don’t want to activate grass we’re going to have growth that’s out of control and if that signal is always on then we’re going to have a cancer okay so the first thing I’ll tell you about Rast is rath is something that we call a proto-oncogene proto-oncogene a proto-oncogene has a very nasty sounding name but it turns out to be a pretty innocuous thing a proto-oncogene is a gene whose protein product in this case wrasse whose protein product placed some central role in an important cell decision this case being growth and commonly growth and division are the important roles that proto-oncogenes play your body is full of proto-oncogenes because your body has to control cell division right now I’m gonna tell you how one way we can screw that process up let’s talk about what’s happening here in this activation first you might look at this and say well that sure looks like a g-protein Kevin because G proteins were things that bound to guanine nucleotides and when they got stimulated they replaced a gdp with a gtp and they became active and that activation caused something to happen and the answer is that wrasse is a type of g-protein rass is a type of G proach it binds to guanine nucleotides it gets activated by the binding of GTP and just like g proteins grass is an inefficient enzyme what does it do well like the g proteins it cleaves GTP back to GDP so this signal turns itself off unless something happens okay if something stops this enzyme from converting GTP back to GDP this R ass is going to be left in the on signal and the cell is going to be continually getting the message divide divide divide divide how does that signal get stuck on a really dandy way is mutation okay mutation change in the sequence of DNA can change the sequence of amino acids in the protein that’s coded by that DNA if we mutate a proto-oncogene we can

change the proto-oncogenes function so that it no longer is functioning right and now the cell divides uncontrollably we have just created an oncogene get rid of the proto-oncogenes are the result of mutation proto-oncogenes are the starting things unmutated I’ll give you a little scary thought before we go to our song for the for the day ok the mutation that can cause wrasse to not be able to cleave gtp involves the change of a single base inside of the wrasse coding amino acid number 11 I believe it is normally has a glycine if you can you take that glycine to any other amino acid this protein will leave wrasse in the GTP state that’s one mutation folks when you wonder why people worry about pollution and the air they breathe the food they eat the water they drink the reason is because they don’t want to mutate any more than necessary because one mutation your hosts not a pleasant thought that’s not a pleasant thought quick question you know I say sr2 I I said SR – I met SH – I apologize yeah I like that the genus name for is Sark which is SR and I was thinking that when I said that but is sh2 domain okay this is a song about signaling a limerick oh my god I forgot I’ll do two next time listen to the tune of the sound of silence by Simon & Garfunkel biochemistry my friend it’s time to study you again mechanisms that I need to know are the things that really stress me so get these pathways planted firmly in your head and sad let’s start with that a nephron membrane proteins are well known change them binding this hormone rearranging cells without protest stimulating on G alpha s to go open up and displace its GDP with gtp because of epinephrine active G then moves aways stimulating at cyclase so a bunch of cyclic am p vines – kinase and then sets it free all the active sites of the kinase has a weight triphosphate because of I can’t carry two muscles are affected then breaking down their glycogen so they get a lot of energy in the form of lots of g1p and the synthesis that could make a glucose chain all refrain because of epinephrine now I’ve reached the pathway end going from adrenaline here’s a trick I learned to get it right linking memory to flight or fright so the mechanism that’s the source of anxious fierce reappears when I make and Efrain okay guys bad singing