if you're feeling overwhelmed and exhausted by the intensity of AP Bio as you prepare for the AP Bio exam or a unit 4 test don't worry you've come to the right place in this video we'll be reviewing all of unit 4 that includes one cell communication cell signaling and Signal transduction two feedback and homeostasis three cell division and the cell cycle and four cell cycle regulation cancer and apotosis I'm Glenn wolkenfeld also known as Mr W and I love teaching b i o LG y to help you study I've put together a checklist that you can download at apbio succombs 4.1 to 4.4 part one cell signaling the big picture cells are constantly communicating with one another it's a basic feature of Life cells are never really on their own they're always in populations or they're in multicellular organism so there's direct cellto cell communication that you see here where there's some kind of Junction between two adjacent cells and molecules can pass between those two cells and that enables one cell to change the behavior of the other there's also communication that happens through signals so here you have a cell that's producing a molecule it's secreting that molecule into the bloodstream or into the extracellular fluid and that message is going to be picked up by a Target cell these signals are known as ligans and they are basically two kinds if the LI the signal is traveling a long distance through the bloodstream from a gland to another part of the body that's called a hormone when cells are in relatively close proximity to one another they produce local regulators and that's for short distance cellto cell communication what are lians ligans are signaling molecules many ligans are hormones and we'll discuss some in depth in this review what they do is they bind with receptors based on complimentary shape and here I've represented that very simply with a kind of circle and an arc but because this is biology you know that the shapes will be extraordinarily complex like enzymes and substrates binding leads to a cellular response and the mechanism by which that happens is going to be most of what we're going to talk about in this video what is Quorum sensor this is a kind of cell communication that's seen in biofilm formation in bacteria and if this seems out of context these are films that can form for example on your teeth leading to the buildup of plaque what happens is that bacteria so here's a single cell be like one of these over here what they do is they release signaling molecules shown over here at number two and those bind to cytoplasmic receptors so those are receptors that are actually inside the cell they're not on the membrane surface when the signal exceeds a certain intensity so when there's a lot of cells around that's a quorum and those signals will be binding with the receptors and that will activate genes and that Gene activation would lead to the expression of for example in this case it looks like what these cells are doing is they're producing a biofilm a polysaccharide that forms that bofilm what's the takeaway twofold the first is that all cells communicate even bacteria and the second is that you should brush your teeth so that you don't get a buildup of bofilm leading to plaque cell signaling involves three phases list them the three phases are reception of a liand that's what's happening over here there's signal transduction where the initial message gets changed into another kind of message that can go into the cytoplasm that often involves amplification of the signal and finally there's a cellular response we're now going to expand on the material in the previous slide what happens during the reception phase of cell signaling the signal molecule also called a li as we've talked about before binds with a receptor molecule here you can see a receptor that has a more realistic depiction and you can see how it's embedded in the phospholipid by layer of the cell membrane that binding is based on complimentary shape what happens during the transduction and response phases of cell signaling the receptor during the transduction phase interacts with membrane proteins to produce a second messenger so something will be happening between here and other proteins in the membrane to bring about this second messenger the second messenger with other relay molecules will bring that message to the cytoplasm activating enzymes or the nucleus where we'll have the activation of genes how is the mechanism of steroid non-polar hormones different from that of w water soluble hormones the hormones we've talked about so far the cell communication mechanisms we've talked about have all involved water soluble hormones but what if the hormone is nonpolar a steroid hormone like estrogen or testosterone in that case these hormones which are nonpolar can diffuse through the phospholipid bilayer and once they're there they can bind with a cytoplasmic receptor that forms a receptor hormone complex and that is capable of diffusing into the nucleus where it acts as a transcription Factor something we'll talk about in AP Bio unit 6 but all you need to know for now is that that can activate genes so the DNA gets made into RNA the RNA goes into the cytoplasm it gets read by a ribosome and gets made into a protein water soluble hormones they're capable of binding with receptors they interact with uh second messengers and they bring about a cellular response and in General these responses are slower but more longer lasting these responses are quicker topics 4.1 to 4.4 part two now that we've had an overview of cell communication we're going to look in depth at an illustrative example epinephrine and G protein coupled receptor systems before we delve into this I want to let you know that I have a song That's a Wrap about cell communication which covers much of this material cellular communication Works through phases three the context for what we're about to review or learn is the fight or flight response and that has effects throughout our bodies one of the effects is the effect on the adrenal glands which produce a hormone that's called epinephrine or adrenaline and that acts upon the liver to get it to produce glucose that goes into the blood as part of the fight or flight resp response epinephrine is also known as adrenaline it's a polar water soluble hormone you can see these hydroxy groups over here and over here here's an amino group this is not going to be able to diffuse into the cytoplasm it's going to bind at the membrane note that epinephrine's effects are widespread but tissue specific so epinephrine is going to get released from the adrenal glands into the bloodstream it's going to go everywhere it's going to touch every cell in your body but only tissues with receptors are going to respond that response will differ based on tissue types so all of these are adaptations that are part of the phlight response so over here we'll decrease digestion because when you're trying to fight off some Mortal threat you don't need to be digesting at that moment you want to increase your heart rate so that you can deliver more food and oxygen to your cells pupil dilation more light you're going to have better senses conversion of glycogen to glucose that gives your cells your muscle tissue more energy to fight or flee a bronchial dilation allows you to get more oxygen into your lungs so you can deliver more oxygen to the cells of the body epinephrine interacts with cells in the liver and it induces changes that causes those liver cells to take stored glycogen that's a polysaccharide and to hydrolize it into the monomers of polysaccharide glucose that glucose then diff fuses into the bloodstream and there it goes to the muscles of the body and to other organs as well and that provides energy to fight or flee as part of the fight or flight response the question for us is how does epinephrine get liver cells to bring about this response so we're now looking at the off State before epinephrine is released and In This Moment the receptor is Unbound there's no epinephrine in the system there's a nearby membrane protein that's called a g protein a g protein is not a receptor it's a membrane embedded protein and it can oscillate between two states now it's off it's inactive nearby the G protein is a membrane embedded enzyme not a receptor but an enzyme that's called adenol cyclas that is actually the correct pronunciation and it's also in the off State and as a result it's not activating the second messenger happens when epinephrine enters the system first thing that happens is that epinephrine binds with a G protein coupled receptor so here's epinephrine and here it's binding with the receptor this is a complicated protein and we've talked about allosteric shifts in relationship to enzymes where when something binds at an allosteric site it can then change the active site well the same mechanism is it work here epinephrine's binding over here and that change kind of ripples through this protein and it induces a change over here now right at this moment the nearby G protein is still dormant it's still bound to GDP GDP is a relative of ADP and it's the low energy form it can oscillate between this low energy form and a high energy form that we're going to see in a minute and that happens when the G protein becomes activated what's the effect on the G protein of epinephrine binding with the receptor well the G protein is then able to interact with the receptor we noted before that the receptor has changed on its cytoplasmic side and that enables the G protein to interact with that part of the receptor and that causes the G protein to discharge GDP that's the low energy form and to bind with GTP that's the high energy form and again notice that this has three phosphates over here just like ATP this only has two phosphates over here like a DP the result is that the G protein now becomes activated so what happens to the G protein once it's bound with GTP it drifts in the membrane It ultimately binds with a denil cyclas this membrane embedded enzyme that activates a denil cyclas and a denal cyclas is substrate is ATP and it converts it into a molecule called cyclicamp which is the second messenger in these G protein coupled receptor systems note that ATP is trip phosphorilated this only has one phosphate and the EMP stands for adenosine mono mono Asin one phosphate what have we done we've taken our initial messenger and we've transduced it creating the second messenger so let's review what we've talked about so far we've talked about reception we have the liant which is epinephrine it binds with the G protein coupled receptor the receptor changes shape on its cytoplasmic side it interacts with the G protein causing it to discharge ggp which is what it's bound to when it's dormant and bind with GTP which is what it binds with when it's active the G protein then in turn can activate a denal cyclas which takes its substrate ATP and converts it into cyclic the second messenger what we're going to look at next is the cellular response the second messenger cylic is going to activate a chain of relay molecules these are called kinases or canes and this activation involves one kinase activating the next kise activating the next I've only put three in this chain but there can be many many more and that's called a phosphorilation Cascade how does that phosphorilation Cascade work the kinases are activated by phosphorilation by gaining a phosphate and once they're activated what they do is they activate the next kinas in the chain so here we have protein kinas one that acts upon protein kinas 2 by phosphor it so now protein kise 2 is active phosphorilated what is it do it activates protein kise 3 by phosphor it I've only shown three but there can be many more in this chain and we get this Domino like effect of one kise activating the next and activating the next once we get to a denal cyclas then each step involves multiple activations denal cyclas will activate many cyclics each of these cyclics will start different phosphorilation chains and the result is signal amplification we had one epinephrine enter the system but by the end and I couldn't of course depict that here but you'll have the activation of millions of enzymes to bring about a massive cellular response in the case of liver cells and the way that they're acted upon by epinephrine the response is activation of the terminal enzyme which is glycogen phosphorus and what glycogen phosphorate does is it converts glycogen again a polysaccharide into glucose a monosaccharide that glucose diffuses into the blood giving you energy for the fight or flight response we've seen how epinephrine working through this G protein coupled receptor system can mobilize this massive cellular response this is incredibly quick and it has to be because it's part of the fight or flight response but after the threat has been escaped from or dealt with the system also needs to be shut down and that needs to happen quickly as well to explain that I'm going to show you this excerpt from my cell communication wrap enjoy back to the LI of the receptor it only stays for a moment before it diffuses away so when the thread is gone the Cascade gets shut down with no adrenal secretion the receptor Unbound G protein drops the phosphate and bound to GDP it goes back to sleep stops its activity bound to GDP it no longer stim Ates a thenal little cyclace which no longer creates cyclicamp so the second message stops kise phosphorilation quickly drops as other enzymes protein phosphatases clip off phosphates turn off kesis glycogen phosphor stops hydroling glycogen so blood glucose normalizes liver cells return to their resting state I love how G proteins let cells communicate I want to acknowledge how difficult and complex some of these Concepts can be and I want to encourage you to go to learn dasm ology.com and with a free trial you can do the tutorials and you can use our unit reviews and it's going to really help you to get on top of this material setting you up for Success on your unit test or the AP Bio exam topic 4.5 feedback and homeostasis what is homeostasis what are feedback mechanisms and how do they connect to homeostasis homeostasis is the tendency of a living system to maintain its internal conditions at a relatively const con an optimal level your body temperature for example stays around 37° C 98.6 fit despite fluctuations in the external temperature the changes in your body to maintain that temperature that's a great example of homeostasis feedback is when the output of a system is also an input so here we have some system here's the thing that's coming out and feedback is when it feeds back into the system so the output is also an input and feedback can do two things one is connected to homeostasis it can allow organisms to maintain homeostasis as they respond to internal and external changes just as I told you with temperature or it can accelerate internal changes and drive a process towards a conclusion this is generally connected with what's called negative feedback and this is connected with what's called positive feedback let's talk about set points what is a set point how are set points used in negative feedback first a word about the method here we're going to talk about this in relationship to your home heating and cooling system it's much easier to understand this before we look at the biological examples so a set point is where you set the thermostat it's the value around which a homeostatic process fluctuates so above the set point for the thermostat is 68° F in negative feedback that output of the system feeds back to the system in a way that decreases the system's output so here we have the set point here's a measurement of the temperature the set point is above the temperature that'll send a signal to turn on the furnace that'll generate heat heat feeds back to the system there's a thermostat over here with the thermometer that will increase the temperature and then when we get to 68° fah the set point the system will turn off negative feedback promotes homeostasis returning a system to its set point how can antagonistic negative feedback loops be paired to promote homeostasis so same goal keep the temperature at 68° well here we have a negative feedback system that responds when conditions are above the set point so temperature 70 the set point is 68 what will you do you'll have a signal that turns on an air conditioner that will put out cool it's a real word and that will feed back to the system and eventually it'll get the system to turn itself off there's been Cooling and we've therefore lowered the temperature but we still have a heating system and if the temperature goes below the set point then that system would turn on it would release heat that would feed back to the system and that would wind up turning the system off so we have paired antagonistic systems one for cooling one for heating now we're going to look at some biology let's talk about how feedback Works in blood sugar homeostasis it's important to your body to maintain your blood sugar levels your blood glucose levels the main hormone that controls that is insulin and it's a negative feedback system in response to high blood glucose levels after eating a sugary or a starchy meal your pancreas will release the hormone insulin just represented here as a triangle in the liver insulin will bind at a receptor over here and that will unleash a signaling Cascade and that talks to a glucose transporter that's a channel that allows for facilitated diffusion if glucose is in higher concentration outside than inside the cell it'll diffuse into liver cells and the glucose will get converted into glycogen which is a storage polysaccharide or it'll get converted into fat blood glucose levels down homeostasis restored but as with our home heating and cooling system insulin is paired with another hormone so let's explain how insulin and glucagon maintain blood glucose homeostasis our blood glucose has a set point about 90 millgram per deciliter above the set point the pancreas will release insulin eat a big meal insulin gets released and your liver fat and muscle cells which aren't shown will absorb glucose and stored away as glycogen below the set point that's when you've gone a little while without eating what'll happen is that the pancreas will release a second hormone called glucagon and that will induce the liver to convert its stores of glycogen into glucose glucose goes into the blood homeostasis is restored an important AP Bio skill is explaining what happens when systems get disrupted and here we're going to explain how blood glucose homeostasis breaks down in type two diabetes that's also called adult onset diabetes but increasingly it's happening in teens and even children due to the Obesity epidemic in the United States we're going to look at normal metabolism first which we just discussed here we see insulin in response to a high blood glucose level is binding with the insulin receptor there's a signaling cast that causes the glucose channel to open there's glucose absorption into the cells blood glucose level Falls homeostasis restored in people with type 2 diabetes what happens is that the cells become insulin resistant there's glucose in the blood there's insulin released from the pancreas but The Binding of insulin does not lead to the signaling Cascade and because of that the glucose Channel remains closed because of that blood glucose level stays high and that damages organs and tissues breakdown of homeostasis leading to type 2 diabetes we just discussed adult onset type 2 diabetes how does that compare with type 1 diabetes type one is also known as juvenile diabetes it's an autoimmune disorder and basically what happens is that cells of your immune system attack the pancreas cells that produce insulin therefore those cells can no longer secrete insulin and therefore even in response to a high blood glucose level insulin is not secreted that can only be treated by insulin injections type 2 diabetes we've just discussed also called adult onset and that involves insulin resistance where the receptor is become insensitive to the insulin signal all of the biological feedback loops that we've talked about so far relating to blood sugar have involved negative feedback loops what about positive feedback loops how does positive feedback work explain how positive feedback works during child birth so in positive feedback the output of a system feeds back into the system increasing the system's activity and output it doesn't involve quieting that leads to homeostasis it involves acceleration it drives a biological process such as child birth to a conclusion after which the system shuts down in child birth the growth of a baby activates uterine stretch receptors the uterus among other things is a big muscle when that muscle is stretched out it sends messages to the brain the brain releases oxytocin a hormone that oxytocin then circulates in the blood when it's picked up by receptors in uterine cells that leads to more contraction that increased contraction leads to more oxytocin release and ultimately that continues until the baby is born explain how feedback leads to fruit ripening if you were to pause the video and take a look at this diagram I'll bet you that you could figure it out this is a positive feedback system ripening in Fruit leads to the release of a hormone that is a gas it's called ethylene ethylene receptors in nearby fruit pick up the ethylene and that induces additional ripening and more ethylene production that increased concentration of ethylene accelerates the ripening process and all the fruit leading to more ethylene So eventually all the fruit ripens in Fruit shipping you can prevent that by pumping carbon dioxide into the storage container where the fruit are and that suppresses the ethylene and that's how you can ship fruit long distances at learn biology.com we understand why students struggle with AP Bio it's a hard course the material is complex the vocabulary is ridiculous and the pace is withering it's natural to feel overwhelmed and inadequate to get an A or a four or a five you need an easier way to study and that's why we created learn biology.com it has quizzes it has flashcards it has interactive tutorials about every topic in the AP Bio curriculum it has a comprehensive AP Bio exam review system use learn biology.com and you'll gain the skills and conf Ence that you'll need to Ace your biology course and to crush it on the AP Bio exam so here's your plan go to learn biology.com we've got free trials from June through March for both teachers and students you won't believe how much you'll learn topic 4.6 the cell cycle on a big picture level what does mitosis do list three of its key functions in living things note for this question that mitosis as it often is is synonymous with eukaryotic cell division mitosis duplicates the chromosomes of a eukaryotic cell transmitting that cell's entire genome to its daughter cell so here you have the parent cell it's got two chromosomes here those chromosomes have been duplicated now they're being pulled apart and now you have daughter cells each with two chromosomes and each one is going to be an exact clone of its parent cell in a multicellular organism like you and me mitosis is how an organism grows and repairs itself remember that you started life as all multicellular beings do as a single cell in a unicellular UK carot like a parium or an amoeba mitosis is how reproduction occurs describe what happens during the cell cycle the cell cycle as you can see in this diagram can be divided into two main phases so the outside Orange part of the circle that's interphase this yellow part over here that's mitosis or mphase represented by the letter M during interphase you can subdivide three basic phases but the cell doesn't appear to be dividing during interphase the first is G1 and during G1 the cell increases in size G1 stands for growth phase one during s which stands for synthesis you have d DNA replication or chromosome duplication and during G2 growth Phase 2 you have the growth of the structures that are required for cell division during mhase you have mitosis separation of the chromosomes followed by cyto canis so at the end you have two daughter cells that are clones of the parent cell describe the phases of mitosis we begin with interphase during which the cell grows and replicates its DNA during that time it doesn't look as if it's dividing but DNA replication for example has occurred during prophase chromosomes which are spread out as what's called chromatin during interphase they condense into these x-like structures the nuclear membrane disintegrates and spindle apparatus which is these fibers over here you can see the entire apparatus in the next phase start to grow from each centrosome during metaphase the spindle fibers grab onto the chromosome and they pull and push them to the cell equator if you can sort of Imagine a line running down from top to bottom that would be the cell equator I talked about this x like formation that the chromosomes are in that's because each chromosome is doubled and consists of two clones called sister chromatids during anaphase the spindle pulls the sister chromatids apart and starts dragging them to the opposite ends of the cell at the the same time there are what are called non- kineticore microtubules a kineticore is like a handle on the chromosomes that these spindle fibers used to pull the chromosomes apart but there are other fibers that basically push on one another and that causes the cell to elongate during til phase a new nuclear membrane starts to grow around each set of chromosomes the chromosomes spread out into their interphase formation so you can't really see them anymore and nucleis reappears in each cell it disappeared during interphase the nucleis makes ribosomes and ribosome production shuts down during most of mitosis finally during cyto canis the cell splits apart into two daughter cells I have a great song about mitosis and I'll put the link below mitosis chromos R meta anop phase divide UK carot SC from one cell to two mitosis how cells renew explain the importance of the g0o phase of the cell cycle basic idea here is that not all cells go through the entire cell cycle so if you have highly specialized cells like a nerve cell or a muscle cell they'll leave the cell cycle and they'll enter into g0 after which they won't divide certain stimuli however can induce cells in g0 to reenter the cell cycle but for the most part the nerve cells that you have the nerve cells that you're going to have which is why a traumatic spinal cord injury is something that you can't recover from topic 4.7 regulation of the cell cycle I'm Mr W from learn biology.com where we believe that interaction and feedback is what leads to deep substantial learning we're so sure of that that we provide a money back guarantee that comes with your subscription describe the role that checkpoints play in regulating the cell cycle cell cycle checkpoints are moments when the cell checks its internal conditions and decides whether to progress to the next phase of the cell cycle if certain molecules are in the right concentration then the cell continues through the cell cycle and if not the cell moves into g0 or might initiate what's called apotosis we'll explain that in a moment which is called programmed cell death the primary checkpoints to know about for AP Bio are the G1 checkpoint over here the G2 checkpoint and the M checkpoint what is apotosis I've talked about that several times note that the second p is silent apotosis is programmed cell death it's part of a signaling Cascade that involves the mitochondria and the nucleus it's highly regulated which is very different from cell death that results from traumatic cell injury cells are broken down into cytoplasmic fragments that are called BBS you can see see some of those over here and over here and blbs are consumed by cells of the immune system preventing cellular debris and enzymes from damaging nearby cells what are cyclin and cyclin dependent kinases cyclin and cycl dependent kinases are important internal Regulators of the cell cycle the cell cycle is regulated by outside signals but also by internal conditions cyclin are molecules whose concentration Rises and Falls throughout the cell cycle so like for example you can see that cycl e Rises right before the S phase cyclon a Rises right before G2 the cell has mechanisms to read the level of these cycling concentrations kinases which we discussed previously in the context of cell communication those are molecules that activate other molecules often by phosphor them they're not shown and cycl depend kinases or cdks are kinases that respond to rising and falling levels of cyclon levels now we're going to put that all together and see what some of the mechanisms are that regulate cell division explain how the interactions between cyclin and cycl dependent kinases control the cell cycle so cdks here they are over here are present at a constant level throughout the cell cycle by contrast the level of cyclin that we saw in the prev previous slide rise and fall when cycl levels are high the cyclin bind with cdks to form a complex called maturation promoting Factor but a good way to remember that is just think of it as mitosis promoting Factor because once you have mpf that allows the cell to pass through the G2 checkpoint and actually divide during mphase however the cycl is broken down and that allows the process to repeat in each daughter cell when it grows to the appropriate size and gets ready for cell division we talked about the cell cycle now let's talk about disregulation of the cell cycle what's the connection between cell division and cancer what are the two types of genetic mutations that are connected to cancer cancer is a disease of unregulated cell division as opposed to cells staying in place doing what they're supposed to do they become Rogue players pursuing their own destiny at the cost of the organism mutations in genes that are called Proto anco increase cell division by creating too many growth factors growth factors are things that stimulate cell division within a cell itself or within other cells and there are other kinds of genes that are called tumor suppressor genes and what they do is they remove cell division Inhibitors the kind of checkpoints that we've seen in previous slides so in normal cells you have the brakes those are tumor suppressors and you have the accelerator those are growth factors but they act at appropriate times when cells become cancerous it can be for one of two or actually both reasons you can have mutated tumor suppressors that can't prevent cell division even when cell division shouldn't be happening and you have growth factors that promote cell division at unneeded moments describe how a mutation in the Ross Proto Anor Gene can induce a non-cancerous cell to become cancerous what we're going to do now is really cool because we're going to connect what we've learned about the cell cycle and its control to what we learned about previously relating to cell communication so Ross is a g protein over here and as a protooncogene it only becomes active when an outside growth signal binds with Ross's coupled receptors so here we have binding that activates Ross it picks up GTP that sets off a phosphorilation Cascade and that leads to cell division so this is in a healthy normal system Ross only gets activated when there's a li When Ross becomes cancerous when it mutates from a protooncogene to an enco gen then it becomes constitutively active and constitutively means it's part of its nature to be active normal Ross is only active it only only binds GTP when the receptor binds a liant but this Ross which is an enco Gene is constitutively active it's binding GTP even in the absence of a growth signal and because it's always active the growth factor over here is overproduced and that results in too much cell division this is connected with about 30% of human cancers describe how a mutation in a tumor suppressor Gene such as P5 3 can contribute to the development of cancer p-53 is a tumor suppressor Gene when cells experience DNA damage a signaling Cascade activates p-53 so here we have DNA damage it's detected there's a signaling Cascade and now p53 is activated if the damage can be repaired then what p-53 will do is it'll halt the cell cycle while DNA repair enzymes fix the damage so we're going to fix up the DNA that's what's happening over here if the damage is too great then p-53 will initiate a whole signaling Cascade that will cause the cell to initiate apotosis so either we have repaired DNA that occurs while the cell cycle is halted or the cell will self-destruct Cancer's been prevented if mutations lead p53 to become nonfunctional then the cell will continue to divide even with damaged DNA so here we have DNA damage it's been detected but p-53 can't do anything about it therefore there's no stop signal the cell will continue to divide and that'll increase the chance of the cell acquiring further mutations that can lead it to become cancerous again disregulation of a signaling Cascade disregulation of a cell cycle repair mechanism leading to cancer here are your next next moves on your journey to AP bios sucess number one go to learnbiology tocom sign up for a free trial of our AP Bio curriculum we guarantee your four or five and then watch this next video