welcome to our chapter 2 lecture for human physiology this chapter is all about cell physiology and remember how we talked about levels of organization in the previous lecture we said that we start with the chemical level where you have atoms and then build those into molecules and then molecules come together to build cells and since a cell is a basic unit of a living thing it's really important that we understand those cells so we'll spend quite a bit of time this semester talking about cellular level functions now we'll also talk about a lot of things in the other levels as well so certainly organ systems is kind of our main perspective for the semester we haven't quite gotten there yet but we will within a couple of lectures and looking at things from a systems perspective really makes a lot of sense when you're talking about trying to understand the whole human body but to understand an organ system you need to understand the organs and in order to understand organs you have to understand tissues and so you have to understand cells so our understanding of cellular level function is part of our important foundation so let's go over a few basics about the cell a typical human cell is somewhere in the neighborhood of 10 to 20 micrometers in diameter and in our first week in lab we talk about what a micrometer is right it's a very tiny unit for measuring tiny things like cells so we had said that a meter is something like a yard if you're familiar with what a yard is so like a yard are the markers on an american football field or think about the width of the average door that's going to be something in the neighborhood of a meter take that meter divide that into a thousand equal parts and those are all millimeters so there are 1 000 millimeters in a meter so millimeters are those tiny little measurements on a metric ruler very very small take that tiny millimeter and divide that into a thousand equal parts and we get micrometers so there are 1000 micrometers in a millimeter which means there are a million micrometers in a meter so these are tiny units for measuring tiny things and why do we care about the size of things it gives us some perspective it helps us understand something about the structures that we're talking about we have a context within which to understand like okay i get what organ level size is but what's cell level size and that can give you some important information to think about what you're talking about so it's easy thinking about size when it's something that you can visualize right like an organ that you can see with the naked eye that's a little bit easier to think about but when something's super super tiny and we can only see it with the microscope it's helpful to have some idea of scale or size of the objects that we're talking about so as we said most cells are in the range of 10 to 20 micrometers in diameter but there is quite a bit of variability the largest human cell is a human egg and that can be in the neighborhood of 140 or so micrometers in diameter now there are lots of cells that can be longer than this but usually the width of a cell is still going to be in this range that we're talking about something like a neuron could be many centimeters long likewise with a skeletal muscle fiber but that's pretty unusual when you think about the trillions of cells in the human body most of them are still going to fit within this range and this average range is a useful thing to remember because later on down the line we'll talk about sizes of other kinds of cells and it will help you understand like okay what are the bigger things what are the smaller things and then you're also going to be seeing many of those things through the microscope in your second lab so all of that put together will help you understand cells and tissues so most cells have three major subdivisions there's the plasma membrane the nucleus and the cytoplasm so we'll briefly talk about each of those three things and then we'll focus in on each of them the plasma membrane can also be called the cell membrane and you really want to keep in mind that you don't say cell wall that's a completely different thing if you've had microbiology or plant biology classes then you've seen that some cells have a cell wall but mammal cells do not human cells do not so plasma membrane or cell membrane is the correct way to refer to it the plasma membrane defines the inside and the outside of the cell the fluid inside the cell is called the intracellular fluid or icf and then the ecf is the extracellular fluid the fluid outside the cell a plasma membrane is selectively permeable so permeable meaning that things can get through it things can go across the plasma membrane but in a selective way so not just anything not just any time the plasma membrane is going to control the movement of molecules between the two fluid compartments right so we can say the icf and the ecf are two different fluid compartments icf within the cell ecf outside of the cell so all cells have a plasma membrane typically a cell is going to have a nucleus although there are some exceptions to that like mature red blood cells but generally speaking cells will have a nucleus it's usually near the center of the cell although that can be a little bit variable and you'll see some examples for the second week of lab often if a cell is elongated like a simple columnar epithelial cell the nucleus may also be elongated and then more toward one end of the cell you can also have cells like adipose cells fat cells where the inclusion of fat that's in the cell is so big that it kind of pushes the nucleus off toward the side but most of the time a nucleus will be somewhere around the center of the cell a nucleus has a double layered membrane and when we talk about our plasma membrane we'll see that it's made out of a phospholipid bilayer when we say for the nucleus that has a double layered membrane that means two phospholipid bilayers and we'll see more about that in a little bit the nucleus contains the dna for the cell and the dna is the genetic blueprint so kind of like how a blueprint tells you how to build a house the dna tells you how to build a cell but it's also more than that it doesn't just tell you about structure it also tells you about function because the dna directs protein synthesis and proteins might be structural but they can also be functional like enzymes so your dna says what kind of enzymes you have in the cell then it's going to say what kind of functions that cell can perform so basically the nucleus acts kind of like the brain of the body it's the control center so all of our human cells have plasma membranes for the most part they have a nucleus as well the stuff that's in between the nucleus and the plasma membrane that's the cytoplasm so everything that's between the nucleus and the plasma membrane is the cytoplasm that's where we have the organelles the organelles are like tiny little organs and that's literally what the word means so the organelles are to the cell what your organs are to your whole body so it's dividing up jobs essentially certain organelles do certain things for the cell just like your organs each do something in particular for your body this is really critical in a cell for the separation of chemical reactions you would have learned in your chemistry prerequisite class that some chemical reactions can interfere with one another in a cell there's all kinds of chemical reactions going on all the time so it's important to separate them from each other so they don't interfere with one another so each organelle is specialized to do particular jobs for the cell the cytosol is the fluid between the organelles we often refer to it as semi-liquid because in some places it can be more watery in some places it's more gel like so it's variable in its consistency it is also the site of many important chemical reactions and later in this chapter we'll get to some specific sorts of reactions that you would see inside the cytosol as well as specific chemical reactions that you might see within particular organelles so here's a picture of a generalized cell so most cells in the body are going to look something like this and we can see that there's a plasma membrane here's the nucleus and then everything in between the plasma membrane and the nucleus that's all cytoplasm including all these various things in different colors those are the organelles and then the cytosol is just the fluid or semi-fluid part that's in between those organelles when we look at cells through the microscope we don't see things in all these different colors right this is just to make them stand out so that we're understanding better what we're seeing some cells do have natural pigment but most cells are transparent there's no natural pigment so you have to stain them to make them show up under the microscope so we add dyes or stains to make different things show up and most of the slides that we look at will make the plasma membrane and then the nucleus stand out most of the cells that we are going to look at you're not going to see these organelles first of all they're too small so the power of the microscopes that we use in the laboratory are not enough to usually see individual organelles also in terms of the number of things that you're seeing here don't expect that to be completely accurate it is true that there's like one big rough er and it tends to surround the nucleus it's attached to the smooth er it's showing lots of mitochondria there can be hundreds or thousands of mitochondria in a given cell depending on what kind of cell you're talking about so there could be lots and lots of golgi's as well so this is not an exact representation but it's giving you a general idea of what does the average cell look like so we'll go through each of the organelles and there's a good summary table in your book that goes through all the different things that you're going to find in the cytoplasm that can be really helpful as a study tool so let's talk about the endoplasmic reticulum or er your book describes it and i love this little phrase as an interconnected fluid-filled membranous system and i just love that as a descriptive phrase it really says a lot and there are two different versions of er there's the smooth and the structure there is more like interconnected tubules or tiny tubes the rough er structurally is more like flattened out sacs of membrane which are again interconnected with each other they're also interconnected with the smooth er so we'll see some visuals on this shortly the other thing that makes the rough er both structurally and functionally different from the smoothie are is that it has ribosomes so the ribosomes are on the surface of the er the outer surface and they're bumpy and that's why it's called rough er the job of the ribosomes is to help with protein synthesis so in a cell you take the dna and you make little molecules called messenger rna that go out of the nucleus to the rough er to the ribosomes and then you start building your proteins so the ribosomes on the rough er are not the only ribosomes in the cell there are also ribosomes called free ribosomes that are in the cytosol they are actually attached to pieces of the cytoskeleton so they're not literally freely floating around it was believed when they were first discovered that they were just freely floating around and that name kind of stuck but they're not just floating around they are attached to a structure of the cell but back to the er let's take a look at some more specifics on the rough and the smooth er so the job of the rough er is to synthesize proteins and often lipids and release them to the lumen or the open part of the er and we're going to see what that is in a moment some of these products that are made by the er are going to ultimately be secreted from the cell so certainly something like a hormone is generally made to be secreted so it can be a messenger for some other cell in the body the enzymes that are made by the rough er might stay in the cell and function there or they might be secreted a lot of the products made by the rough er will become new plasma membrane or maybe parts of organelles so basically the rough er is making anything that the cell needs for itself or that needs to be secreted from that cell so we said when the rough er starts making products they end up in the lumen the open part of the rough er and then it's not finished yet once it's there that protein can be modified you can take pieces off you can add things to it and it's kind of on its way to becoming a final product so often in the figures in the book you'll see a little line drawing like this which is really nice for giving some perspective on what you're looking at there's really not a lot of point in delving into the details of a figure until you understand like big picture what are you looking at here so we're thinking about okay average cell now we're looking at the rough er a little bit of smoothie r here and then we're taking out that rough er to look at it close up and then here's the smoothie r and then these are micrographs so a micrograph is a photograph through a microscope the power of microscopes that we have in our labs the maximum magnification would be 1000 times meaning an object that you look at would look a thousand times bigger than it actually is what we're looking at here are electron micrographs or photographs taken through an electron microscope which is far more powerful than the type of microscopes that we would have in the lab so these can see down to the organelle level you wouldn't be able to reach that with the type of microscopes that we have in the lab electron microscopes can be like a hundred thousand times magnification or even more than that so with this massive magnification you can even see the little tiny dots that are the ribosomes and then here they are on the surface that's why it's called rough er because the ribosomes make these little bumps and so the ribosomes are critical in the protein synthesis process so if you've had an intro bio or a majors bio class you would have talked about protein synthesis and how you get from the dna in the nucleus to producing a protein here in the er for our purposes we just need to know that the ribosomes and the relationship with the rough er allows you to make proteins so you start that process on the outside and then that product moves into the inside into the lumen of the rough er and once it's in the lumen you can see all these are interconnected so stuff can move around in there and once it's in the lumen it's still being processed it's not a final product yet so the smooth er is the next step in the production line or the manufacturing process for the cells in most cells the smooth er is going to take what you started in the rough er and then continue to process it and then send it off to the next step which is to go to the golgi complex so for most cells the smooth er is an in between step manufacturing would go rough er smoothie r to golgi but there are some cells that specialize so the smooth er can be modified to do different kinds of jobs in particular cells so in some cells it can be specialized to do lipid synthesis so this is what happens in some of our endocrine glands that secrete steroid hormones steroid hormones are all based on cholesterol and we'll learn a lot more detail about that later in the semester you don't have to worry about too much detail right now you're always responsible for the amount of detail that you see in your lecture notes anything that's in your lecture notes i could ask you about on an exam another way that smooth er can specialize is in liver cells it's designed to detoxify harmful substances and then in muscle cells the smoothie r is specialized to store calcium so there are a few possibilities for specializations of the smooth er in certain types of cells but most of the time it's part of the production line you start making products in the rough er they go to the smoothie r then they go to the golgi so we're noting in the comparison with the rough er that the smooth is more like little tubes as opposed to flattened sacs that we see in the rough er and we can even see that in the micrograph so most of the things that are in this category of organelles are what we call membrane-bound organelles so they have a membrane to them and those membranes are very similar although perhaps not absolutely identical to the plasma membrane they still have the same basic structure as a plasma membrane and we're going to be talking about that in quite a bit of detail the golgi complex is our next structure in the production line or manufacturing process sometimes it's called the golgi apparatus so that might be a term that you've heard before and golgi is just the name of a person so it does pop up in a couple other places in biology the golgi complex is layers of flat sacks of membrane and it's different from the rough er because the rough er is all interconnected the golgi is more like stacked up layers of membrane and sometimes we call these sacks of membrane cisterni which just basically means a container so the job of the golgi is to process the products that started at the er usually rough er to smooth er and then to golgi and it'll process them into their final form it will also sort them out and send them to where they're supposed to go so the golgi can make transport vesicles that will take those products to locations that might be staying inside the cell or they might be leaving the cell and there's a coating on the vesicle a vesicle is basically just a little sphere of membrane and a coating goes on it that basically says what the product is and where it's supposed to go so it's kind of like the mailing center where you put a label on the package that says not only where it's going but what's inside it so that it gets to the right place some cells that do a lot of secretion have secretory vesicles that come from the golgi and those are generally found in cells that specialize in secretion by the process of exocytosis this would be common in hormone-secreting cells so their entire job is to secrete hormones by the process of exocytosis so let's talk a little bit more about those terms secretion is usually the word we use when a cell or maybe a larger structure like a gland releases a product that's going to be used in some way let's contrast that with excretion excretion is usually referring to a waste product that you want to get rid of so you excrete wastes but you secrete hormones for example now i'm not going to say that everybody uses those words that way in every instance but that is a really good general way of thinking about it right so we secrete things that we need um we excrete things that we want to get rid of although there can be some crossover there right like sweat has a usefulness to it but you're also getting rid of waste products there so sometimes it becomes a little bit fuzzy but generally secretion is what we do with products we're going to use and excretion is what we do with waste products that we want to get rid of exocytosis is a particular process by which we can do secretion release something from the cell and we'll be looking at that a little bit more closely i really like this figure it's very simple and cartoony but it really gives you a nice idea of what's going on with the manufacturing process with the production line in the cell so you need the dna in the cell to tell you what you're supposed to do and then you send some information out here to the rough er the ribosomes help you build the beginnings of those proteins which then end up in the lumen of the rough er and the little dots that it's showing you here the green and the yellow that's meant to represent two different kinds of products and what would literally be happening is tons of different kinds of products are all being made at the same time but it's just showing us as an example two different things represented by different colors so they kind of move through these interconnected sacs they can get to the smooth er which is still interconnected with the rough er and then from the smooth er kind of pull off these little pieces of membrane and that becomes a vesicle so a vesicle is just a little sphere of membrane and sometimes those vesicles can come directly from the rough er as well it's just showing you an alternative pathway but the most common pathway is to go rough er smooth er to golgi so you notice when that package is sent to the golgi everything is mixed up right both kinds of products are in there right now and then it makes it to the golgi and once it gets to the golgi the golgi sorts it out so it's separating out the two different kinds of products and it sends them out in separate packages and in this example one of those vesicles is actually becoming an organelle it becomes a lysosome within the cell in this example it's showing us a vesicle that's going to move to the plasma membrane and fuse with the plasma membrane and dump the product outside so we can say this is secretion right the product is being secreted it's leaving the cell and it's being secreted by the process of exocytosis so let's take a closer look at the golgi complex it's only showing one in the cell but there can potentially be hundreds of golgi's within a particular cell especially if it's a cell that needs to do a lot of secretion you would have more golgi's potentially hundreds so here we're seeing that vesicle coming over from the er with a mix of products inside by the time you get to the other side of the golgi you've sorted out the products and then those vesicles are either going to stay in the cell or that product might get secreted from the cell via exocytosis this is taking a little bit of a closer look at exocytosis it's just generally giving us a visual as always you are responsible for the level of detail that's written in your lecture notes it's really good to have these visuals to go along with it so here's a vesicle it's showing it with a phospholipid bilayer same as the plasma membrane right they won't be identical to each other but this is only showing the phospholipid bilayers in this case so there's way more to a plasma membrane than that and we'll get to that eventually but here we're seeing that the basic structure is the same the foundation is a phospholipid bilayer so now when that vesicle approaches the plasma membrane it's made out of the same stuff so we can just fuse right to it and then dump that product to the outside so this is exactly what exocytosis is about you take a vesicle that was formed inside the cell fuse it to the plasma membrane and now that product was secreted from the cell and the cell got a little bit of extra plasma membrane in the process in most cells you're going to be doing a combination of exocytosis and endocytosis so exocytosis can add to the membrane whereas endocytosis takes pieces out of the plasma membrane and in fact most cells do more endocytosis than exocytosis so you might even have vesicles like this from the golgi that don't have a product inside that you're trying to secrete it's just water and other small solutes what you're trying to do is just add more plasma membrane so that's another way to use the golgi and the process of what looks like exocytosis but you're basically just adding more plasma membrane endocytosis on the other hand you start with a product that's on the outside and the plasma membrane kind of starts to surround it and then forms a little vesicle and then that vesicle pinches off and now it's inside the cell and it's going to go somewhere in the cell and do whatever it was designed to do okay so we've taken a look at the production line let's look at some other kinds of organelles so there are the lysosomes and the lysosomes are kind of nondescript in their appearance they just look like a little sack of membrane there wouldn't be anything that distinguishes them by their appearance what makes them special is what's inside them so they contain enzymes called hydrolytic enzymes meaning water is used to lyse or break apart different kinds of molecules so the job of the lysosome is to digest cellular debris so just stuff that's left over in the cell that you don't need and other things like old organelles or maybe if you're talking about phagocytic cells like white blood cells that eat up bacteria they're going to use their lysosomes to break down the bacteria one important job for the lysosome is to break down stuff that cells brought in by endocytosis so remember endocytosis that we just looked at a moment ago the membrane surrounds the substance you bring it in in a vesicle and then depending on what that substance is you might use the term pinocytosis or phagocytosis pinocytosis is a process you do with fluids so just things with small dissolved solutes not big chunks and that word pinocytosis means cell drinking and then there's phagocytosis which involves large particles so that's cell eating so both pinocytosis and phagocytosis are endocytosis so endocytosis is the broader term pinocytosis and phagocytosis are subcategories of endocytosis so you bring stuff in and then you digest it or break it down with the enzymes in the lysosome and then the cell can use that digested material if there's anything that's not useful it will just leave the cell your body will excrete it as a waste eventually this figure is just showing us some different versions of endocytosis here we see there's the product on the outside and the plasma membrane kind of surrounds it and it pinches off into a vesicle there's a whole involved process in what gets taken in by endocytosis we're not learning about all the details of that but it's very common that it's this version which is receptor-mediated endocytosis so in order for the cell to know that it's supposed to do endocytosis typically something has to bind to a receptor so something that is in the plasma membrane that once that molecule binds the cell knows that it's supposed to do so this is also showing endocytosis just receptor mediated which is actually the more common type this is showing what you might expect to see with phagocytic cells like white blood cells so here is a phagocytic cell maybe some bacteria in the body the cell surrounds it and brings it in takes it over to a lysosome lysosome fuses with the vesicle that brought in the bacteria and breaks it down and then this is showing a micrograph of an actual white blood cell phagocytizing an old red blood cell i like these pictures up in the corner because they're showing us electron micrographs and this is super super tiny level right like this is a picture through an electron microscope that's showing vesicles at different stages like this one it's just kind of starting to form here it's almost all the way formed it's just kind of cool to be able to see it so it's always worth spending some time with your figures to help you get visualizations of processes that we talk about in this figure it's showing us two similar appearing organelles they're basically just little bags of enzymes but the type of enzymes and their specific jobs are quite different so here's the lysosome that we're just looking at with hydrolytic enzymes peroxisomes are usually a bit smaller but they still just look like little vesicles they contain oxidative enzymes the job of oxidative enzymes is to use oxygen to remove hydrogen from other molecules and as you do that you detoxify the molecule you may recall from your chemistry that oxygen is really good at yanking electrons away and yanking hydrogens away from other molecules so if you can pull apart a toxic molecule you can detoxify it you can make it less dangerous so here's where the fun is going to start when we're talking about mitochondria there are some important aspects to get for the structure of mitochondria different portions of the mitochondria have different jobs and it's going to be very important to understand each of those jobs so mitochondria have a double membrane and we talk about those as the inner and the outer membrane the inner membrane has folds that are called christie and it is very common that if you see folded membrane the purpose of that folding is to create more surface area and in this case that's because the stuff that we need to make atp or the majority of our atp is embedded in this inner membrane so you want a lot of it and to fit a lot of it into a small area you need to fold it up inside the inner membrane is the matrix and the matrix is a gel so you have an outer membrane an inner membrane and then the matrix inside the inner membrane now mitochondria play a role in apoptosis which is a term for programmed cell death we're going to talk about that more but just kind of hold this in your mind for when we get there for the moment our conversation about mitochondria is going to revolve around the manufacture of atp so mitochondria do the majority of your atp manufacture so you convert energy from your food molecules into usable energy for the cell in the form of atp or adenosine triphosphate and it's that third phosphate bond that is the high energy bond that we want to get so the energy that is in the chemical bonds of your food molecules like a glucose molecule for example you can't use that directly and eventually we'll talk about why that is but basically it's just too much energy all at once you need to take the energy in your food molecules and make it into atp which is very very tiny bits of energy and then use it in the form of the atp so you're going to make atp so that you can break it down into adp or adenosine diphosphate plus inorganic phosphate which is how we say the p sub i you say inorganic phosphate and then the energy that you're getting out of that is what you're using to do whatever it is that you're talking about muscle contractions or movement of molecules across the plasma membrane for example might need energy basically anything that the cell needs energy for it's using it in the form of atp so this is that structure that we were just talking about the orange is showing you the outer membrane of the mitochondrion so mitochondrion is singular mitochondria is plural so there's that outer membrane here's the inner membrane with all these folds that we can call christie so remember we fold that up so that we can fit more of it into that space and then this is the matrix so the gel inside the inner membrane is the matrix and then there's this space between the inner and outer membrane we just call that the inter-membrane space so all of this is important what happens in the inter-membrane space is important what happens on the inner membrane is important what happens in the matrix is important and we're going to be talking about all of those things and here we have a nice little micrograph of a mitochondrion so a cell that's not super metabolically active doesn't have very high needs for atp might have like a hundred or a few hundred a cell that's very large that has high needs for energy like certain skeletal muscle fibers might have thousands of mitochondria so basically cells make the number of organelles that they need to perform their specific functions although interestingly mitochondria don't come from the dna in the nucleus it's not shown in this picture but mitochondria have their own dna it's called mitochondrial dna and a lot of times mitochondrial dna is used to show evolutionary relationships and mitochondrial dna is actually more similar to the dna of things like bacteria so microorganisms that do not have nuclei have little circular pieces of dna and that is what mitochondria have so i'm not going to go into a ton of detail about this but the idea is and we'd be talking about over a billion years back in cell evolution at some point there was a little prokaryotic cell whose membrane is represented now by the inner membrane and then that cell was phagocytized brought into another larger cell by endocytosis and this outer membrane is the idea of the vesicle that brought that in but then instead of that little microorganism getting digested by the cell they started living symbiotically so if you're interested in cell evolution and the evolution of particular organelles there are two organelles that are like that that have their own dna and the nuclear dna doesn't say anything about them and so that's mitochondria for animal cells and then plant cells also have mitochondria and in addition to that they have chloroplasts which again similarly have their own dna and the nuclear dna doesn't say anything about them so that's just a little tidbit there's nothing you need to worry about so focus on the structure think okay we've got the outer membrane and then there's a space between the inner and outer membrane that's going to be important there's the inner membrane itself and then there's the matrix inside so we're going to talk about the process of cellular respiration which is how a cell makes atp the three major steps of cellular respiration are glycolysis the citric acid cycle and oxidative phosphorylation which is going to involve the electron transport chain so these events do happen in a particular order so let's start with glycolysis glycolysis happens in the cytosol so we're not in the mitochondria yet we're in the cytosol remember we said the cytosol has a variety of chemical reactions that includes significantly the ones that we're talking about here in glycolysis a glucose is broken down into two pyruvic acid molecules so a glucose is a six carbon molecule pyruvic acid is a three carbon molecule so we end up with two of them from breaking apart a glucose and that does happen in a series of steps it doesn't happen all at once and we're going to see in these reactions that there are always a whole bunch of reactions involved in a process and we're going to see why eventually so breaking down a glucose into two molecules of pyruvic acid which can also be called pyruvate that will get you two atps for each glucose that you started with which is not particularly efficient but you're getting some atp out of it the other thing that you get is you're attaching hydrogens to carrier molecules and we're going to talk more about that so here are those three steps we'll go through details of each so right now we've looked at this piece a little bit so glycolysis is happening in the cytosol you break down we're just going to talk about glucose for now we'll talk about other kinds of molecules in a little while glucose broken down into pyruvate you get two atps and you also make some hydrogen carriers just by attaching hydrogens to a carrier so if we look at the three steps here so the three major steps being glycolysis citric acid cycle and oxidative phosphorylation which involves the electron transport chain all of the steps give us some atp but what we're seeing here is we're going to get more out of the last process but we're still getting some out of glycolysis so we said we're taking that one six carbon glucose molecule and breaking it down into two three carbon molecules that are pyruvate or pyruvic acid and that happens in ten separate steps if you were to take a biochemistry class you would need to know all 10 separate steps as well as the enzymes that perform each step for our purposes it's fine to just know the level of detail that's in your lecture notes so this part is showing us that we are getting two atps out of the process so we take adp and add on the inorganic phosphate to make atp this is showing us attaching hydrogen to a carrier so there's nad becomes nadh and we'll address those hydrogen carriers more in a bit okay so that first part glycolysis happened in the cytosol we get two atps out of it we attach hydrogens to some carriers now we're going to take a look at the citric acid cycle it can also be called the krebs cycle or the tricarboxylic acid cycle the pyruvic acid or pyruvate gets transported into the matrix of the mitochondria so think back to what we're just talking about in terms of structure the matrix is inside the inner membrane of the mitochondria and pyruvic acid can diffuse right through those phospholipid bilayers once there the pyruvic acid gets converted into acetyl coa and then the acetyl-coa enters the cycle so it's a cycle because you'll literally see everything turning in a circle and you always come back to what you started with so it's a series of reactions where you come back to what you started with along the way you're going to produce carbon dioxide as a byproduct or a waste product of the process so we breathe in so that we can get oxygen in and we're going to see where that's used we haven't seen that yet this is the part of cellular respiration where you produce carbon dioxide so when you breathe out what you're trying to do is get rid of the excess co2 that's in the body and this is where it comes from your process of making atp it's good to know that the o2 in the co2 didn't come directly from the oxygen that you breathed in it's coming originally from the glucose that you started breaking down back in glycolysis we mentioned in glycolysis that hydrogens get attached to carrier molecules that also happens here in the citric acid cycle and i just put the details in here it's basically the same thing for glycolysis i just put the details in one spot only so there are two different versions of hydrogen carriers we have nad and fad and these are both derivatives of b vitamins so one way that vitamins are important to us is that they participate in the process of making atp nad stands for nicotinamide adenine dinucleotide fad is flavin adenine dinucleotide that's more just for your interest you're never really going to have to say those words or know the details of those words if you remember nad and fad and that they are hydrogen carriers you'll be good so nad can carry one hydrogen it becomes nadh fad can carry two hydrogens don't worry about any differences there for our purposes they are both doing the same job and we'll see what they do in the third part of cellular respiration along with everything else you get two more atps for each glucose that you started with so we always track this as though you're starting with one glucose molecule now of course in the cell you're actually breaking down lots of glucose molecules step by step all at the same time but it's easier to track like how much atp is getting made if you just think about it with one glucose molecule so if we started with one glucose back in glycolysis then we got two pyruvic acids that each participated in the citric acid cycle and that will give us two more atp so we're still talking about a very low yield of atp this figure shows us quite a bit of detail about the citric acid cycle you don't have to know every detail here as i said you're always responsible for the level of detail that is written in your lecture notes so the text-based slides that we look at but often it can be helpful to look at just a little bit more detail to give the information some context so i like how it's showing you where this is happening in the matrix of the mitochondria it's showing you the three basic steps and then which one are we highlighting here now we can see all the details of the citric acid cycle so here's our three carbon pyruvate so we got two of those coming in from glycolysis remember the hydrogen carriers as well as the pyruvate can just diffuse right through the phospholipid bilayers and the membranes of the mitochondria so you turn the pyruvate into acetyl coa at this step you get a carbon dioxide you're also attaching hydrogen to a hydrogen carrier so the pyruvate gets processed into acetyl coa and that's how we start the cycle so this reaction happens and then this one and then this one and then this one and you keep going around and you ultimately come back to where you started so that's why it's called the citric acid cycle even though you don't need to know each individual step it's useful to recognize what's going on here so each one of these reactions would have an enzyme that does it this is another situation that if you were in a biochemistry class you would need to know every step every enzyme we're looking at this from a much bigger picture but it's still helpful to see that at some steps you've got co2 being produced you've got hydrogens being attached to carriers and here is where you're getting the atp here's where you produce the fadh2 and then here's another nadh so for each pyruvate that comes in it gets converted to acetyl coa and that lets us have one turn of the cycle so we got one atp from one turn of the cycle but two pyruvates came in from glycolysis right so glucose broke down into two pyruvates so we can do two turns of the cycle producing two atp at this step altogether so now between glycolysis and the citric acid cycle we've got 4 atp not a lot but some and we've got a whole bunch of hydrogen carriers so the atp we can just use in whatever way is needed in the cell the hydrogen carriers are going to participate in the next step where we're going to get a lot more atp those of you that absorb better from reading definitely read through the details of these notes i'll go through them in just a moment but i'll also talk through the whole thing while we look at some pictures so here we're going to be talking about the third part of cellular respiration so we're talking about the electron transport chain and the process of oxidative phosphorylation to produce our atp remember that glycolysis happened in the cytosol citric acid cycle happened in the matrix of the mitochondria electron transport occurs on the inner mitochondrial membrane so the pieces that are called electron carriers exist embedded within the inner mitochondrial membrane so if there's electron carriers where are these electrons coming from they're going to come from the hydrogens hydrogen atom contains one electron right hydrogen is one proton one electron and also recall that when you do things like bind atoms to each other to make a molecule they can be sharing electrons so when you're moving electrons around you're moving energy around like there's energy contained within a chemical bond like say a covalent bond for example because you're sharing electrons so if you move electrons around you're moving energy around and every hydrogen has one electron we attached hydrogens to the hydrogen carriers in both glycolysis and citric acid cycle we don't do anything with them until we get to the electron transport chain so they are going to enter the chain and as they do that you take away the hydrogen right so we created them so you could carry the hydrogen to the electron transport chain and then you yank the hydrogen off and you yank the electron from each hydrogen and you start passing the electron along in a series of steps and eventually that electron ends up landing on oxygen so we call oxygen the final electron acceptor so remember oxygen is really really good at grabbing electrons from other things so the other stages of cellular respiration did not require oxygen directly it's this step that requires the oxygen and we're going to see where it fits in so when we yanked the hydrogen off the carrier and then we yanked the electron from the hydrogen we ended up with hydrogen ion now it's just a proton and that hydrogen can move across the inner membrane it will be transported across the inner membrane but remember there's two membranes there so the hydrogen isn't leaving the mitochondria it's getting stuck in the inter membrane space so what we're ending up doing is creating a gradient we're packing in hydrogen ions in that intermembrane space when you create a gradient things want to flow down a gradient but hydrogen can only flow back across the inner membrane at certain points plasma membranes and the membranes that we're talking about for any of our organelles are built so that you cannot get ions across unless you build a specific way to allow that to happen so the hydrogen ions you have this gradient they want to flow back across to the matrix but they can only do that at certain points the channels that allow the hydrogen ions to flow through contain an enzyme called atp synthase and a lot of times enzymes sound like what they do so atp synthase synthesizes or makes atp so that enzyme gets activated by the hydrogen ions flowing by and so you end up creating 28 atp for each glucose that you started with back backing glycolysis so this is where the high yield of atp is so steps three and four in this list we can call the chemi osmotic mechanism because there's a chemical reaction coupled to the flow of a substance across a membrane so the chemi part is the chemical reaction the osmotic part is the flow across a membrane and because we're using oxygen as the final electron acceptor to make the atp we call this oxidative phosphorylation so oxygen is required to make the bulk of your atp right so this is where you get the high yield of atp you need oxygen to do this now glycolysis can happen anaerobically meaning without oxygen but it wouldn't be very efficient right you'd be making only small amounts of atp now we do that sometimes we'll talk more about those kinds of processes right now let's focus on the need for oxygen in this particular process and what are we going to do with this oxygen so it grabs an electron and we have all these hydrogen ions around so you're going to end up binding the hydrogen ions to the oxygen and get water this water is what we call metabolic water it means you made it inside your body with your metabolism which is just like a catch-all term for all the various chemical reactions that you do this water was not water when it entered your body it was hydrogens from a variety of molecules and oxygen from breathing in oxygen now humans form limited amounts of metabolic water this is not some tremendous amount of water but it's also not insignificant one thing you're noticing here is wow we sure have a lot of steps and why does it need to be that way the importance of that is that if you were to take a glucose molecule or any nutrient molecule and try and break it apart all at once to get the energy out so much energy would be released that it would kill the cell it would like melt it apart because there would be so much heat so it's necessary to release the energy in small steps so that you can package it into atp and then you're fine you can manufacture the atp and use it for energy but you didn't generate excess heat at any point you are generating some heat right your body heat comes from the various chemical reactions that you're doing in your body that give off energy but you're creating reasonable amounts of heat so that your body can handle it and you have ways to dissipate the heat like sweating for example if you have too much heat in the body okay so all those steps probably didn't make sense yet when you're just thinking about the words most people are going to need to understand the visuals to really get the process here i'm definitely a visual thinker if i can't visualize a process i can't understand it and a lot of people learn that way so definitely use that to your advantage when this comes up make drawings or copy figures something like that to really help you with the visualization an important thing to do here is to make sure you're oriented to the figure i would say that's always important with any figure that you look at so make sure you understand what you're seeing like this doesn't make any sense until you look at the bigger context here so here's our cytosol this is the outer membrane of the mitochondria this is the inner membrane of the mitochondria and this is the inter-membrane space so this would be the matrix recall that glycolysis is happening out here so there's a little bit of atp made out here in glycolysis you also attach hydrogens to carriers which can diffuse through these membranes and end up in the matrix you're also attaching hydrogens to carriers in the matrix with the citric acid cycle and producing a little more atp that again can diffuse right out of the mitochondria so you can use it wherever you need it in the cell now we want to look at all the pieces that are embedded in this membrane don't worry about the details of what each of these molecules are called just broadly we'll call them the electron transport chain this is atp synthase that enzyme that we mentioned our hydrogen carriers they either started in the matrix because they came from the citric acid cycle or they were made in glycolysis and diffused here either way there are a couple of different points where the hydrogen carriers come in the nadh comes in at this step and the fadh comes in at this step you don't have to worry about that detail the visual is just to help you understand the level of detail that's written in your notes so this first complex takes the hydrogen from the carrier yanks the electron from the hydrogen and now it starts passing this electron around at some of the steps when you pass the electron you give off energy right like it drops an energy level what do you do with that energy you take the hydrogen ion what was left when you pulled the electron away from the hydrogen you got hydrogen ion and then you can carry that hydrogen across the inner membrane we have another step where you take the hydrogen and then take the electron pass the electron along every so often when you pass the electron it drops an energy level you use that energy to bring the hydrogen ions across the inner membrane and so they accumulate in the inter membrane space broadly what's going on here is you're yanking hydrogens off of hydrogen carriers that you made expressly for the purpose of doing this you yank the electron away from the hydrogen you pass the electron from molecule to molecule when the electron drops an energy level you use that energy to bring the hydrogen ions into the inter membrane space sometimes you might hear that expressed as pumping the hydrogen ions across the membrane into that space so they're accumulating here and they can't go anywhere unless you give them a hole that they can move through we'll come back to that in a second they're not capable of going through this phospholipid bilayer or this phospholipid bilayer unless you give them a way to do that now the way that you give them to do that is atp synthase but let's hold that for a second so we yanked our hydrogen off we yank the electron away we're passing the electrons along and then something has to be the last thing to grab the electron it needs to be something that's really really good at grabbing electrons away from other molecules that's what the oxygen is for so the oxygen that you're breathing in this is the very specific reason why you need the oxygen it's going to grab the electron it's going to combine with some of the hydrogen ions because not all of them went across the membrane there's still some left over here and when they combine you get water so that's your metabolic water coming back to the atp synthase that provides a hole that the hydrogen ions can go through if you put a whole bunch of hydrogen ions here they want to move away from there they can't move in this direction because there's nothing to let them through they can only go this way and as the hydrogen ions flow across it's kind of like turning a crank it energizes the crank and as you turn the crank you produce atp so you take adp and inorganic phosphate that's just floating around and you put it together into atp so this is where you get the bulk of your atp from this is a really nice summary of the processes that we've just been talking about if we start with glucose and just counting it as one glucose to begin with we do glycolysis we get a couple of atp which we can use for whatever we need it for we also attach hydrogens to a couple of carriers and we get pyruvate or pyruvic acid that diffuses into the mitochondrial matrix you make it into acetyl-coa you start turning the citric acid cycle for each turn you get another atp and each pyruvate gets converted into acetyl-coa and each acetyl-coa as they go through make one atp so we total two from one glucose at the beginning of glycolysis we're also producing hydrogen carriers here and here and here so glycolysis attaches hydrogen to carriers but you do a lot more of that in the citric acid cycle you won't use all those hydrogen carriers until you get to oxidative phosphorylation and the electron transport chain so between the two atp that we got from glycolysis again counting from one glucose molecule and then the two atp that we get from the citric acid cycle you get another 28 from oxidative phosphorylation and electron transport for a total of 32 atp from each glucose molecule if you're looking at an older source of information it might say something like 36 to 38 atp in recent years some things were recalculated and now that number is a little bit lower but it's still a significant amount of atp with a vast majority of it coming from electron transport and oxidative phosphorylation now remember we said a little while ago that while you're doing chemical reactions you're producing body heat so not all the energy that was in a glucose molecule gets converted into atp some of it becomes body heat sometimes i hear people say the energy is lost it's not exactly lost right you're using it it's heating up your body which we need the point is that any time you're transferring energy from one molecule to another that energy transfer cannot be a hundred percent efficient that's just the laws of physics what we didn't use to actually make atp we use to create our body heat if we have more than we need we have ways to dissipate heat from the body like sweating you can also shift where your blood flow is going like sending more to the skin will help you like radiate some of that heat away from the body we also talked about this as though it were only glucose it's not only glucose the building blocks of fats and proteins can be used to make atp they can be broken down into intermediate molecules in the citric acid cycle so intermediate molecules just means all those things that participate in the cycle so you can break down a fat you can break down a protein make it into intermediates in the citric acid cycle and get atp out of them it is very common that we break down fats in order to make atp it's less common that we would break down proteins because usually proteins we would want to use for structure or other functional molecules like enzymes but we can break down proteins if we need to to make atp and as we talk about different kinds of tissues and organs throughout the semester we'll mention what is their most common like mode of metabolism what do they use as an energy source more often and it can vary like in skeletal muscle it depends what kind of skeletal muscle fibers you're talking about some types of fibers are more likely to use glucose some are more likely to use fats it can depend on how active you are so we'll get to those details later in the semester and remember that atp that we make out of cellular respiration can be used for all of the cells energy needs so if you need to transport something that requires active transport like exocytosis and endocytosis they're both active transport they require atp there are a whole bunch of other things that are active transport that we will be talking about in this first unit there's also things like muscle contractions so for your heart to beat for your skeletal muscles to move your body for your smooth muscle to move food through your digestive tract or adjust the pressure in your blood vessels that's all going to take atp this is just a nice little visual on what would happen if you had uncontrolled oxidation of food basically an explosion so we cannot release heat in those quantities in small amounts of time and survive that so we have these very elaborate step-by-step ways of releasing energy from a molecule so that it's useful to us in our body so we've seen some complicated stuff at this point let's look back at this simpler picture whenever you find yourself getting lost in the details step back from it what's the bigger picture that we're talking about here so we're breathing in to get oxygen into our body we need the oxygen for this step in order to do this step we had to do the citric acid cycle which is where the carbon dioxide is coming from that we breathe out so the connection between saying respiration meaning breathing like stuff that happens through the respiratory system you breathe the oxygen in you breathe your co2 out now you know why you breathe oxygen in and why you breathe co2 out so to review glycolysis occurs in the cytosol you get a couple of atp you attach hydrogens to carriers that you're going to use in the final steps the pyruvate that you create in glycolysis diffuses into the mitochondrial matrix you make it into acetyl coa and then that starts turning the cycle you make a couple more atp and you attach hydrogens to more carriers all of the hydrogen carriers that came from glycolysis and from the citric acid cycle can now participate in the final steps where we have oxidative phosphorylation and the electron transport this is a system or i usually say electron transport chain because that's the terminology i'm used to so this is where we make the bulk of our atp it's where we use our oxygen and make metabolic water so remember that if we think about starting with one glucose to simplify it you have to do a whole bunch of steps and you end up with your pyruvate here's where your hydrogen carrier comes in here's where you got your atp you send your pyruvate into the mitochondrial matrix where you convert it into acetyl coa that starts turning the cycle you make some co2 as a waste product you attach hydrogens to some more carriers and you make a little bit more atp the hydrogen carriers wherever they came from they can diffuse into the mitochondrial matrix the molecules of the electron transport chain yank the hydrogens from the carriers yank the electrons from the hydrogens so now you end up with hydrogen ion you pass the electrons along whenever they drop in energy level you can use the energy to move the hydrogen ions into the inter membrane space across the inner membrane they accumulate there because they don't have a way to move across except for this limited pathway of going through the atp synthase as they flow across you're turning the crank and making the bulk of your atp and then that atp can diffuse wherever in the cell that you need to use it now remember again the oxygen here you need oxygen as the final electron acceptor as long as you have oxygen to grab the electron the chain keeps going glycolysis keeps going citric acid cycle keeps going electron transport and oxidative phosphorylation keep going as long as you have oxygen and keep in mind we're only looking at one electron transport chain here right remember we said this inner mitochondrial membrane is all folded up and we call those folds christy why do we fold up membrane usually it's to create more surface area so we fold it up so we can fit a whole bunch of these electron transport chains in a single mitochondrion and then each cell can have hundreds or perhaps thousands of mitochondria and then we've got all these cells in our body so we're making lots and lots of atp to use in whatever ways we need now let's say we're exercising really hard and because we need a lot of atp when we exercise we're using up a lot of oxygen we can start to run low on oxygen now if you were entirely anaerobic you would die because you wouldn't be able to produce enough atp anaerobically to have a human body survive but you can start doing a little bit more anaerobic metabolism you can do glycolysis without oxygen now of course you can't do the electron transport chain without oxygen because if there's nothing to grab that electron there's nothing to keep the electrons moving forward here so the electrons will back up in the chain if they back up then you also won't be able to do these steps of taking the hydrogens from the carriers and then you also won't do the citric acid cycle you'll still do glycolysis though so you can do anaerobic metabolism in limited ways in the body certain types of muscle fibers specialize in anaerobic metabolism but there's a consequence to that because it's a relatively low yield of atp we'll worry about that when we get to muscle and we'll talk about muscle fatigue and oxygen debt and what all that has to do with this for now we want to keep in mind that you make atp through multiple pathways but that oxidative phosphorylation and electron transport and that chemiosmotic process where hydrogen flows across the membrane and you do the chemical reaction of creating atp from adp and inorganic phosphate that's where you get the bulk of your atp so this is necessary for survival in the long term if you don't have enough oxygen to keep doing this meaning some of your electron transport chains are without oxygen to grab that electron and be the final electron acceptor then a lot of these back up and you make less atp here and then the citric acid cycle also won't work you can still do glycolysis anaerobically so this can be a challenging process to understand break it up into the pieces make sure you know your terminology keep looking at the visuals and you'll be able to put together the picture it's going to take some time and like anything that you study you should start out with those basics take some notes what are the definitions of terms if you don't know the terms you won't understand the larger process so it's one step at a time learn the structure of the mitochondria what are the different pieces of the mitochondria called what are the different processes called where do they happen and then come back to the processes glycolysis is fairly simple citric acid cycle is a bit more complex but the details you need to know about it are fairly straightforward it's oxidative phosphorylation and that electron transport chain that are a bit more complex right so we always start with the simple stuff terminology and we start working our way up to small concepts and finally getting to big concepts and you always want to keep in mind like why are we doing this we're doing this because our body needs atp to do things like muscle contraction how do we move our body how does food move through our digestive tract how does our heart beat how does our brain think we need atp for all of these things and keep in mind that even though we've focused mostly on glucose we also said that other nutrient molecules in particular fats can be broken down into molecules that participate in the citric acid cycle and so we can use other kinds of nutrient molecules to make atp as well and we'll finish up the rest of chapter two in another video