How long can you hold your breath? Most people can only manage between 30 and 45 seconds before they need to start breathing again. Just 3 to 4 minutes without oxygen is often enough to cause brain damage or death. Fun fact: before I started BOGObiology, I worked as a medic for a number of years. We often referred to the rule of three: humans can survive about three weeks without food, three days without water, and just three minutes without oxygen. The oxygen clock starts ticking the second the person stops breathing. This is why we'd drive really, really fast to get to all of our calls. But why do we need oxygen so badly? How do our cells use it, and what happens to them if they don't get it? This video will review the process of cellular respiration in order to answer these questions and more. This is definitely going to get pretty complicated particularly when we get to the reactions portion with the Krebs cycle and electron transport chain. If you'd like to download a set of guided notes I've left a link to them in the video description. Ok here we go! In respiration our goal is to use glucose and oxygen in order to generate ATP plus some water carbon dioxide and heat on the side. Notice the similarities between this cellular respiration equation and the equation for photosynthesis. The two processes are essentially complementary. ATP is a universal cellular energy currency which the body spends to do virtually every action that keeps us alive. There are two kinds of cellular respiration aerobic and anaerobic. Aerobic respiration requires lots of oxygen but it also gives you the most bang for your glucose buck. Anaerobic respiration occurs when there is very little or no oxygen. It yields a little bit of energy but not nearly as much as aerobic respiration. This video will mostly cover aerobic respiration. If you'd like me to make a detailed video about anaerobic respiration / fermentation be sure to let me know in the comments. In eukaryotes respiration takes place in the cytoplasm and in the mitochondria the mitochondria have inner and outer compartments and a portion of cellular respiration takes place in each one. The outer compartment is called the inter membrane space and the inner compartment is called the matrix. Aerobic respiration consists of three major steps; glycolysis the Krebs cycle and the electron transport chain. In glycolysis uses up glucose and also invests a tiny bit of ATP in order to generate some more ATP. The krebs cycle generates still more ATP and some carbon dioxide as a waste product. We also throw in a little bit of water to the krebs cycle but not much. The electron transport chain uses up oxygen and generates water plus a lot of ATP. So, now that we've seen the overall picture we're going to dive into the process itself beginning with glycolysis. The first step in both aerobic and anaerobic respiration is glycolysis which occurs in the cytoplasm of the cell. This step does not require any oxygen which is why it's common to both types of respiration. We'll start with a molecule of glucose which has 6 carbons but we need to break it into pieces in order to use it. To jumpstart this breakdown, we're going to invest 2 ATP into glycolysis glycolysis will eventually yield 4 ATP for a net yield of 2. It first forms a very unstable compound called Fructose 1 6 bisphosphate and the formation costs 2 ATP. Then this molecule splits into two kinds of 3 carbon molecules; DHAP (dihydroxyacetone phosphate) and PGAL (glyceraldehyde 3-phosphate). Eventually all the D HAP converts into PGAL; a more useful molecule for our purposes. Note that glyceraldehyde-3-phosphate is a really long name so luckily it has several nicknames. Different parts of the world use GALP, G2P, GADP etc all to refer to the same molecule. After still more chemical reactions the PGAL is going to be converted into pyruvate. The process of converting PGAL into pyruvate eventually generates 4 ATP and it also involves two molecules of something called NADH. The pyruvate making process generates waste products of electrons and protons. NADH is known as a mobile electron carrier. It will transport these particles to another set of reactions later on and then come back for more, much like a dump truck. When the NAD+ is loaded up with the electrons and proton, we say it's been "reduced" into NADH. When the NADH is unloaded we say it's oxidized back into NAD+. Remember O.I.L.R.I.G. oxidation is losing and reduction is gaining. Cellular respiration also uses another mobile electron carrier called fadh2. In summary we started with one glucose molecule and broke it into pyruvate and also recharged two NADH. It's often really useful to keep score as we go through the reactions. As we progress, we'll be updating a chart that looks like this. So far we've made four ATP and spent 2. Then we recharged 2 molecules of NADH and zero fadh2. Next up we have the prep steps. These are technically part of glycolysis but my students found it far easier to understand how glycolysis and the Krebs cycle are connected when we outlined this particular set of reactions independently. The prep steps occur in the cytoplasm just like glycolysis. We need to slice and dice the products of glycolysis a little bit in order to use them in the Krebs cycle. During the prep steps we're going to modify our 3 carbon molecule of pyruvate using something called coenzyme A. Coenzymes store energy in their bonds and help enzymes work more effectively. At the end of the prep steps we generate 2 molecules of something called acetyl coenzyme A or Acetyl CoA. We also generate 2 molecules of CO2 and two reloaded molecules of NADH. Notice how pyruvate had 3 carbons and how those 3 carbons get reshuffled into a molecule with two carbons and a molecule with one carbon. We haven't magically lost any carbons anywhere in here they've just been rearranged. Remember also the aerobic respiration produces carbon dioxide as a waste product and this is one of the places that it comes from. Before moving on to the Krebs cycle let's update our scorecard. Here we made zero ATP, 2 NADH and zero FADH2. Now for the Krebs cycle. The Krebs cycle, also known as the citric acid cycle, takes place in the inner compartment of the mitochondria known as the matrix. The Krebs cycle is going to use the products of glycolysis and the prep steps and work to recharge a few ATP molecules and reload a bunch of nadh and another carrier molecule called fadh2. We will cash in these carrier molecules for ATP later on. Each of the following steps are performed by enzymes but the exact mechanisms of how they work are beyond the scope of this video. We're going to kick off the Krebs cycle with something we just made in the prep steps; acetyl co a, which has two carbons. The acetyl co a from the prep steps adds on to a new four carbon molecule called oxaloacetate to form an intermediate molecule. By looking at the diagram so far you can probably guess how many carbons this intermediate molecule has. Two carbons plus four carbons equals six carbons. From here we add a series of enzymes to convert each molecule into the next one. The next molecule is isocitrate which is similar to citrate and also has six carbons. Next we form alpha ketoglutarate which only has five carbons. So what happened to that sixth carbon? It's released in the form of carbon dioxide. Next up is a molecule called Succinyl CoA which has four carbons. Based on the last step you can probably guess what happened to that fifth carbon; it was released in the form of a second molecule of carbon dioxide. Next up is a molecule called succinate which also has four carbons, then comes fumarate which has four carbons, and then malate which also has four carbons. We also add a molecule of water here to get this final molecule. Last we convert the malate back into oxaloacetate where we started and the cycle can begin again. I'm not usually a big fan of memorization but if you're forced to memorize the krebs cycle here's a little trick that I learned in undergrad. "Cindy is kinky so she $%&#s more often". However if you need something a little more g-rated you might go with 'Cindy is keto so she feeds more obnoxiously". So now we've mapped out how the Krebs cycle cycles carbon and where the carbon dioxide waste product comes from. Let's go back in and add in ATP and also add in all of our electron carriers. We reload three molecules of NADH during the Krebs cycle the first when we convert isocitrate into alpha-ketoglutarate and the second when we convert alpha-ketoglutarate into Succinyl CoA. The third is when we convert malate into oxaloacetate. We recharge a single molecule of ATP between Succinyl CoA and Succinate and then we also reload a new molecule called FAD into fadh2 between succinate and fumerate. However all of the above is per molecule of pyruvate and since each glucose is broken into TWO molecules of pyruvate, this cycle can turn twice per molecule of glucose. So let's do a little Krebs Cycle math. One rotation of this cycle makes one ATP 3 NADH 1 FADH2 and 1 co2 but since the cycle turns twice we actually make double that for each molecule of glucose we put in. In total we now have 4 ATP 10 NADH and 2 FADH2. Now let's move on to the electron transport chain. The electron transport chain is the real moneymaker of cellular respiration; in a really efficient cell it can make about 34 ATP per molecule of glucose. This last set of steps is essentially two major parts; the electron transport chain and something called chemiosmosis. The ETC creates a powerful proton gradient with lots of potential energy. The chemiosmosis exploits this gradient to generate recharged ATP. We call these two processes together oxidative phosphorylation. To start with let's review how the e.t.c establishes that gradient. To make the gradient we need a membrane with more protons on one side and fewer protons on the other side. The membrane can have channels in it but they need to be one-way channels to keep the protons from sneaking back to the other side and re-establishing equilibrium. In respiration this gradient occurs across the membrane that separates the compartments of the mitochondria. It's in between the mitochondrial matrix, the inner compartment, and the inter membrane space, the outer compartment. This membrane is studded with protein complexes several of which include proton pumps. These one-way pumps maintain the gradient. NADH and FADH2 are going to deliver electrons and protons to the area on the matrix side of the membrane. Every time an electron contacts one of these pumps it's going to pump another proton from the matrix into the intermembrane space and make the gradient stronger. Where do the protons for the gradient come from? Conveniently they're also delivered by the NADH and the FADH2. But why is the process called a "chain"? This is because a high-energy electron is transported through a chain of proteins. At each step the electron's energy is reduced and that energy is used to do something useful. It works much like a conveyor belt delivering electrons from one protein to the next. Electrons can enter at two different points but they always travel in the same direction. Let's work through the process first a molecule of NADH is broken down into hydrogen, electrons and NAD. This pair of electrons from the NADH are going to flow through the electron transport chain starting at complex I. Look at the diagram and see how many proton pumps you think they will pass through. The pair of electrons delivered by the NADH will flow through three different proton pumps pumps; I, III and IV. Each time they touch one, the pump will suck a new proton into the intermembrane space strengthening the proton gradient. Along the way they will be transferred through to other protein complexes; ubiquinone and cytochrome c, but these complexes don't do any pumping. But what about FADH2? FADH2 also delivers electrons. It delivers them to complex II. Complex II then transfers the electrons to ubiquinone then to complex III, cytochrome C, and then complex IV. The pathway is almost the same it just uses a different on-ramp. To make sure we're on the same page, look carefully at the diagram and figure out how many protons get pumped as a result of one molecule of FADH2. Since FADH2's electrons only make it through proton pumps III and IV, we can conclude that each molecule of FADH2 will result in pumping two protons into the intermembrane space. Regardless of whether the electrons originated from NADH or from FADH2 they need to go somewhere once they reach the end of the electron transport chain. This is where we finally get to understand why oxygen is so important. Oxygen is known as the final electron acceptor in the electron transport chain. The spent electrons bind with protons and oxygen to form molecules of water. Without oxygen to pick up the electrons at the end of the chain, the proteins would become "clogged" with electrons. The pumps would stop working, the gradient would disappear, and then we couldn't recharge any more ATP. Essentially, Cyanide and suffocation in general cause death via electron constipation. Unless oxygen arrives promptly to deal with the "clog" the prognosis is ...crappy! Now that we've discussed how the electron transport chain makes a gradient, we should discuss how the gradient is used. Currently there are a ton of protons in the intermembrane space of the mitochondria and very few in the matrix. This gradient has a lot of potential energy and the protons are desperate to re-establish equilibrium. The only route that flows from the intermembrane space back into the matrix is via the ATP synthase protein. Notice how there is just one ATP synthase passage for every three proton pumps. This means that the competition to leave through the one available exit is pretty fierce. This flow of ions from high to low concentration across a semipermeable membrane is known as chemiosmosis. Every time a proton passes through the ATP synthase protein, it recharges a molecule of ADP back into ATP. It tacks a phosphate group onto ADP making it into ATP. We call this process "phosphorylation". Remember how we figured out how many protons a molecule of NADH and FADH2 would yield under ideal conditions? This is where we cash in those molecules for ATP. For each molecule of NADH, we pumped three protons and can recharge three molecules of ATP. For each molecule of FADH2, we pumped two protons and thus can recharge two molecules of ATP. In total we made four ATP, plus another 30 from NADH, and another 4 from FADH2. So in summary we used both glucose and oxygen to generate carbon dioxide, ATP and a little bit of water. So that's pretty much it on cellular respiration and I hope you found this video useful! If you did please remember to like, comment, and subscribe! See you later!