so our body is made up of several trillion cells and these cells are going to organize into different tissues and organ systems these various tissues and organ systems then are going to function to help us maintain homeostasis in order for our individual cells to survive homeostasis must be maintained so in order to maintain homeostasis these trillions of cells must be able to communicate with each other so what we're going to do in this slide presentation is we're going to review some of the ways where chemical Messengers may bring about responses and cells that process is called signal transduction so trans2 is to convert from one form of energy to another in order for a Target cell and that's what we refer to the cell that is going to respond to a chemical messenger in order for a Target cell to respond to a messenger it must have the appropriate receptor present so in this example imagine we have three different cells with three different receptors but this particular chemical messenger is only able to bind to this one Target cell and thereby bring about a response so in the initial two cells they don't have the appropriate receptor therefore no response occurs when a chemical messenger interacts with a cell and it activates that receptor and brings about a response we call that chemical messenger and Agonist there will be some chemical Messengers that bind to receptors but do not activate receptor they may actually in fact block that receptor from being activated and those particular chemical Messengers are called an antagonist or a blocker now we're going to see there are a couple of different signal transduction mechanisms that may occur within the body and these are going to be broken down based on the type of Messengers that are unified them into two major categories lipophilic and hydrophilic and from our initial lectures we know the significance of that because our cell membrane is primarily a lipophilic barrier so it's going to interact with these Messengers differently so first let's look at the lipophilic messenger and what this picture represents this is the represented blood vessel So within the blood vessel we have these yellow triangles which represent our lipophilic messenger the lipophilic messenger does not dissolve well in plasma so notice that it has to be bound to a a carrier molecule which is indicated by the purple circle the lipophilic messenger which is not bound to the care molecule can then leave the blood vessel and can diffuse directly across the membrane because it's lipophilic and combine to an intracellular receptor from there the messenger and receptor complex will move into the nucleus and it will have an impact on the DNA in an area called the hormone response element this is then going to be transcribed into messenger RNA and then eventually translated into a protein which will bring about a response so lipophilic Messengers are said to act as transcription factors compared to hydrophilic Messengers the effects of lipophilic Messengers tend to take a bit longer to manifest The receptors here may be intra-nuclear as well as within the cytoplasm itself so here's a picture again which is simply demonstrates a blood vessel here we have the yellow diamonds which represent a lipophilic messenger and notice that most of those lipophilic Messengers are going to be bound to in this case the white carrier molecules the blue polygons here represent hydrophilic Messengers so what we'll see is the majority of lipophilic messenger is bound to carry molecules in fact it's usually well over 99 percent is going to be bound that part of the messenger that's not bound is called a free messenger and that's the messenger that can leave the blood vessel and go out to the cells so in this case we show the lipophilic messenger leaving the blood vessel and going into the cell binding to an intracellular receptor and we'll bring about a response but notice what happens is when that leaves the blood vessel notice that a molecule that had been previously bound is now released so we'll always keep what we call this dynamic equilibrium of a certain concentration of messenger that is free and is able to move out of the blood vessel now the hydrophilic messenger it can also move out of the blood vessel just fine also notice that it is not value any type of carry molecule But realize because it's hydrophilic it can't enter into the cell so the the signal transduction method for hydrophilic Messengers must utilize a different mechanism than what we saw with lipophilic Messengers so hydrophilic Messengers are unable to pass through the membrane so they therefore must bind to a membrane-bound receptor okay whereas we saw with the lipophilic molecules they go straight through the membrane the hydrophilic molecules cannot so there are basically three different types of membrane-bound receptors and we're going to go through those here the first type of membrane-bound receptor is what we call an enzyme-linked receptor so the enzyme-link receptor has a receptor on the membrane and it's going to be linked to an enzyme which is typically going to be on the inner surface of the membrane many of these enzymes are kinases and kinase phosphorylate they're substrate resulting in some type of response following so in this case a chemical Messenger will bind to the enzyme-linked receptor it will activate that enzyme or in this case the kinase that will then act on its substrate to phosphorylate it and that will bring about a response the second type of membrane-bound receptor that we'll see is called a channel linked receptor so this will be a transmembrane integral membrane protein and it has a binding site when the chemical messenger binds to that binding site it results in a conformational change which opens up that channel and then will allow the movement of ions in or out which in turn results in some type of a response the third type of membrane-bound receptor is a bit more complicated and it's called a g protein-linked receptor so we have a membrane-bound receptor and it is then linked to a g protein and the g protein has these various components the one we'll highlight here will be this Alpha subunit so in a chemical messenger binds to a g protein-linked receptor it will bind and it will cause that Alpha subunit to dissociate and to migrate through the membrane or along the membrane and it will in turn interact with another structure in this case we'll refer to that as a black box we'll explain what that is on the next slide but whatever that is that it interacts with it eventually results in some type of response occurring so let's look at what this black box may be that the alpha subunit interacts with with a G protein-linked receptor the first thing that black box may be is it may be a transmembrane protein so we have our chemical messenger binding to our g-linked receptor the alpha subunit migrates over and it's going to open up a transmembrane protein which allows ions to move in and out so that's very similar to what we saw with a channel link protein or Channel link receptor so imagine that we have these two things together and we begin this process at the same time what we'll notice is is that the channel like receptor can respond much more rapidly it takes a bit longer for the G protein linked receptor to bring about its response these channels are given specific names a channeling preceptor is oftentimes referred to as a fast Channel and the g protein length receptor is oftentimes referred to as a slow Channel they also can be called fast channels can be called ionotropic channels and slow channels can be called metabotropic channels now the other thing that the G protein linked receptor May activate other than a protein Channel or transmembrane protein is it may activate a activator enzyme and that's what's demonstrated here in this picture now when we begin to utilize this we're going to also introduce these additional terms we have mentioned here that the chemical messenger is referred to as a first messenger so the first Messengers are messengers that can be used to Signal between cells and they're going to bind to a membrane-bound receptor so we have this first messenger binding to our G protein-linked receptor the alpha subunit comes over and it's now going to activate this amplifier enzyme the amplifier enzyme isn't going to act on some substrate and depending on what the enzyme is it's going to create a second messenger so the definition of a second messenger is substances that are generated either within the cell or they are allowed to enter the cytoplasm which will show shortly as the result of the actions brought about by a first messenger so we have the first messenger activating the G protein-linked receptor which activates the amplifier enzyme which results in the creation of a second messenger these will eventually bring about a response within the cell now the second messengers that may be created depend on what enzyme is present which amplifier enzyme is present so these are four of the common second messengers that we will find in our cells cyclic amp cyclic GMP bi-acoglycerol or dag and inositol triphosphate or ip3 so four different enzymes and depending on what enzyme is present will determine which second messenger is produced the first of these three cyclothamp cyclic GMP and dag all will go and will activate a protein kinase and it's by that mechanism that they then bring about a response inositol triphosphate Works differently a nasotop triphosphate or ip3 is going to interact with the smooth endoplasmic reticulum as you will know from your previous biology courses the smooth ER is a site where calcium is stored so ip3 will bind to the membrane of the smooth ER and it will open up a channel and that channel will allow for calcium to move and calcium moves out of the smooth ER into the cytosol once there calcium can interact with a protein called calmodulin and this calcium calmodulin complex then will activate a protein kinase which brings about a response there's one more second messenger and the second messenger that's left is the one that I've referenced here is one which can enter into the cytoplasm as a result of a first messenger and what we'll see is some cells have calcium channels and these calcium channels can respond to the first messenger and open up calcium's more concentrated outside the cell than inside the cell so calcium can enter into the cell once inside of the cell it can bind to calmodulin and then this calcium cow modulin complex can activate the protein kinase and bring about a response so in this mechanism where calcium is let in from outside of the cell in response to the first messenger binding to a membrane-bound channel and calcium and that method or in that situation is also referred to as a second messenger