Respiration

Well I'm going to do some push ups when you are reading this, so why not join me! You see what happened there when you do a single push up? Your arms moved, your shoulders, your back and stomach moved. your heart pumped blood to all those different places. Pretty neat, huh? Well, it turns out that how we make and use energy is a lot like sports or other kinds of exercise. It can be hard work and a little complicated but if you do it right, it can come with some
tremendous payoffs. But unlike hitting a ball with a stick, it's so marvellously complicated and awesome that we're still unravelling the mysteries of how it all works. And it all starts with a marvellous molecule that is one of your best friends. ATP.

Today, I'm going to write about energy and the process our cells, and other animal cells, go through to provide themselves with power.

Cellular respiration is how we derive energy from the food we eat-specifically from glucose, since most of what we eat ends up as glucose. Here s the chemical formula for one molecule of glucose (C6H12O6). In order to turn this glucose to energy, we're going to need some oxygen. Six molecules of it, to be exact. Through cellular respiration, we're going to turn that glucose and oxygen into 6 molecules of C02, 6 molecules of water and some energy that we can use for doing all our push ups.

So that's all well and good, but here's the thing; we can't just that energy to run a marathon or something. First our bodies have to that energy into a really specific form of stored energy called ATP or adenosine triphosphate. People often refer to ATP as the "currency" of biological energy. Think of it as an pound sterling-it's what you need do business in the UK. You can't just walk into a book shop with a handful of Indian rupees and expect to be able to buy anything with them, even though they are technically money. Same goes with energy; in order to be able to use it, our cells need energy to be transferred into adenosine triphosphate to be able to grow, move, create electrical impulses in our nerves and brains. Everything.

Now, before we see how ATP is put together, let's look at how cells cash in on the energy that is stashed in there. Well, adenosine triphosphate is made up of an nitrogenous based called adenine with a sugar called ribose and three phosphate groups attached to it; now one thing you need to know about these 3 phosphate groups is that they are super uncomfortable sitting together in a row-like 3 kids on the bus who hate each other all sharing the same seat. So, because the phosphate groups are such terrible company for each other, ATP is able to do this nifty trick where it shoots one of the phosphates groups of the end of sit creating ADP, or adenosine diphosphate (because now there are just two kids sitting on the bus seat). In this situation, when the third jerk kid is kicked off the seat, energy is released. And since there are a lot of water molecules ust floating around nearby, an OH pairing- that's called a hydroxide-from some H2O comes over and takes the place of that third phosphate group. And everybody is much happier.

By the way? When you use water to break down a compound like this, its called hydrolysis- hydro from water and lysis from the Greek word for "separate." So now you know how ATP is spent, let's see how it's minted-nice and new-by cellular respiration.

Like I said, it all starts with oxygen and glucose. A lot of text books go on saying that through cellular respiration, one molecule of glucose can yield a bit of heat and 38 molecules of ATP. Now it's worth noting that this number is kind of a best case scenario. Usually it's more like 29-30 ATPs, ut whatever-people are still studying this stuff, so let's stick with that 38 number.

Now cellular respiration isn't something that just happens all at once-glucose is transformed into ATPs over 3 stages: glycolysis, the Krebs cycle, and the electron transport chain. Traditionally these stages are described as coming one after the other, but really everything in a cell is kinda happening all at the same time.

But let's start with the first step: glycolysis, or the breaking down of the glucose. Glycose, of course is a sugar-you know this because it's got an "ose" at the end of it. And glycolysis is just the breaking up of glycose's 6 carbon ring into two 3-carbon molecules called pyruvic acids or pyruvate molecules.

Now in order to explain how exactly, glycolysis works, I'd need about an hour of you time,  and a giant cast of finer puppets each playing a different enzyme, and through it would pain me to do it, I'd
have to use words like phosphoglucsosiomerase. But one simple way of explain it is this: if you wanna make money, you gotta spend money. Glycolysis needs the investment of 2 ATPs in order to work, and in the end it generates 4 ATPs, for a net profit, if you will, of 2ATPs. In addition, to those 4 ATPs, glycolysis also results into 2 pyruvates and 2 super-energy-rich morsels called NADH, which are sort of the love-children of a B vitamin called NAD+ pairing with energized electrons and hydrogen to create storehouses of energy that will later be tapped to make ATP.

To help us keep track of all the awesome stuff we're making here, let's keep score?

So far we've created 2 molecules of ATP and 2 molecules of NADH, which will be used to power more ATP production later.

Now, a word about oxygen. Like I mentioned, oxygen is necessary for the overall process of cellular respiration. But not every stage of it. Glycolysis, for example, can take place without oxygen, which makes it an anaerobic process. In the absence of the oxygen, the pyruvates formed through glycolysis get rerouted into a process called fermentation. If there's no oxygen in the cell, it needs more of the NAD+ to keep the glycolysis process going. So fermentation frees up to some NAD+, which happens to create some interesting by products. For instance, in some organisms, like yeasts, the product of fermentation is ethyl alcohol, which is the same thing as all of this stuff (alcohol). But likely for our day-to-day productivity, our muscles don't make alcohol when they don't get enough oxygen. If that were the case, working out would make us drunk, which actually would be pretty awesome, but instead of ethyl alcohol, they make lactic acid. Which is what makes you feel sore after
the workout that kicked your butt.

So your muscles used up all the oxygen they had, and they had to kick into anaerobic respiration in order to get the energy that they needed, and so you have all this lactic acid building up in your muscle tissue.

Back to the score. Now we've made 2 molecules of ATP through glycolysis, but your cells really need the oxygen in order to make the other 30-some molecules they need. This is because the next two stages of cellular respiration-the Krebs cycle and the electron transport chain, are both aerobic processes, which means they require oxygen.

And, so we find ourselves at the next step in cellular respiration after glycolsosis: the Krebs cycle. So, while glycolysis occurs in the cytoplasm, or the fluid medium within the cell that all organelles hang out in. the kerbs cycle happens across the inner membrane of the mitochondria, which are generally considered the power centers of the cell. The krebs cycle takes the products  of glycolysis-those carbon rich pyruvates-and reworks them to create another 2 ATPs per glucose molecule, plus some energy in a couple of another forms, which i'll talk about in a minute.

Here's how: first, one of the pyruvates is oxidized, which basically means it' combined with oxygen. One of the carbons off the three-carbon chain bonds with an oxygen molecule and leaves the cell as CO2. What's left is a two carbon compound called acetyl coenzyme A, or acetyl coA. Then another NAD+ comes along, picks up a hydrogen and becomes NADH. So our two pyruvates create another 2 molecules of NADH to be used later. As in glycolysis, and really all life, enzymes are essential here; they are proteins that bring together the stuff that needs to react with each other, and they bring it together in just the right way. These enzymes bring together a phosopahte with ADP, to create another ATP molecule for each pyruvate. Enzymes also help join the acetyl coA and a 4-carbon molecule called oxaloacetic acid. Together they form 6-carbon molecule called citric acid which is in orange juice.

Fun fact; the krebs cycle is also known as the citric acid cycle because of this very byproduct. But it's usally referred to by the name of the man who figured it all out: Hans Krebs, an ear nose throat surgeon who fled Nazi Germany to teach biochemistry at Cambridge, where he discovered this incredibly complex cycle in 1937. For being such a total freaking genius, he was awared the Nobel Prize in Medicine in 1953.

Anyway, the citric acid is then oxidized over a bunch of intricate steps, cutting carbons of left and right, to eventually get back to oxaloacetic acid, which is what makes the krebs cycle a cycle. And as the carbons get cleaved off the citric acid, there are leftovers in the forms of CO2 or carbon dioxide, which are exhaled by the cell, and eventually by you. You and I, as we continue our existence as people, are exhaling the products of the krebs cycle right now. Good work.

Now, each time a carbon comes off the citric acid, some energy is made, but it's not ATP. It's stored in a whole different kind of molecular package. This where we go back to NAD+ and its sort of colleague FAD. NAD+ and FAD are both chummy little enzymes that are related to B vitamins, derivatives of Niacin and Riboflavin, which you might have seen in the vitamin aisle. These B vitamins are good at holding on to high energy electrons and keeping that energy until it can get released later in the electron transport chain. In fact, they're so good at it that they show up in a lot those high energy-vitamin poweders for the kids are taking these days.

NAD+S and FADs are little batteries, big awkward batteries that pick up hydrogen and energized electrons rom each pyruvate, which in effect charges them up. The addition of hydrogen turn them into NADH and FADH2, respectively. Each pyruvate yields 3 NADHs and 1 FADH2 per cycle, and since each glucose has been broken down ito two pyruvate, that means each glucose molecule can produce 6 NADHs and 2 FADH2s.

The main purpose of the krebs cycle is to make these powerhouses for the next and final step, the Electron Transport Chain.

And now's the time, when you are saying "Sweet pyruvate sandwhiches, Rebekah, aren't we supposed to be making ATP? Let' make it happen. capt'n What's the holdup?" Well friends, your patience had paid off, because when it comes to ATPs, the electron transport chain is the real moneymaker. In a very efficient cell, it can net a whopping 34 ATPs.

So remember all those NADH's and FADH2s we made in the krebs cycle? Well, their electrons are going to provide the energy that will work as a pump along a chain of channel proteins acorss the inner membrane of the mitochondria where the krebs cycle occurred. These proteins will swap these electrons to send hydrogen protons from the inside the very center of the mitochondria, across its inner membrane to the outer compartment of the mitochondria. But once they're out, the protons wantto get to the outer side of the inner membrane, because there's a lot of other protons out there, and as we've learned, nature always tends to seek a nice, peaceful balance on either side of a membrane. So all of these anxious protons are allowed back through a special protein called ATP synthase. And the energy of the this proton flow drives this crazy spinning mechanism that squeezes some ADP and some phosphates together to form ATP.

So, the electrons from the 10 NADHs that came out of the krebs cycle have just enough energy to produce roughy 3 ATPS each. And we can't forget our friends the FADH2. We have two of them and they make 2 ATPs each. And volia! This is how animal cells thhe world over make ATP through cellular respiration.

Now just to check, let's rest out ATP counter and do the math for a single glucose molecule once again. We made 2 ATPs for each pyruvate during glycolysis. We made 2 in the krebs cycle. And then in during the electron transport chain we made about 34 in the electron transport chain, And that's just for one molecule of glucose. Imagine how much you body makes and uses every single day.

Don't spent it all in one place now!