now the ultimate goal in fat metabolism is to be able to deliver some triog glycerides which I'm going to Pro it here is T which remember is the chemical name for a fat molecule or free fatty acids which I'll abbreviate here is FFA which if you recall are the kind of monomer subunits of these fat molecules directly into the bloodstream where they can eventually reach capillary beds like the one that I've drawn here so go ahead and label this it's a capillary bed and it's important that they reach these capillary beds because it's at this point where they can diffuse to surrounding tissues such as muscle or heart tissue for example where they can be taken up by these tissues and oxidized to obtain cellular energy in the form of ATP now I want to remind you that there are three main sources of these triog glycerides or free fatty acids that can enter the bloodstream and so I'm going to go ahead and scroll up here and show you kind of what I've already drawn out here and go ahead and explain it starting off here on the far left I've drawn a cheeseburger perhaps not the best drawing in the world but just to remind us that one of our sources of fat that ultimately reaches our bloodstream is directly from our diet so recall that our small intestine digests our food and packages the fat molecules the tri asil glycerides into protein carrier molecules called kylo micron some fat into our bloodstream is by synthesizing it directly inside of the liver which I've kind of drawn an outline of here now the liver cells are especially equipped with the right type and number of enzymes to be able to convert excess glucose that is the glucose that's not being used for ATP synthesis or glycogen synthesis into fatty acids then like the small intestine the liver essentially packages these fatty acids into triol glyceride molecues and packages them together with cholesterol another hydrophobic molecule into another specialized protein carrier molecule like kyom microns but this one has a slightly different name it's called very low density lipoprotein or vdl for short and this of course is sent off to the bloodstream where it will eventually reach capillary beds and be taken out by surrounding tissues even perhaps atopos cells which might store it up for later use so now that we've got this overview I want to zoom in on one of these steps I want to zoom in on this step here going from glucose to fatty acids inside of the liver which is commonly referred to Simply as fatty acid synthesis and to do this I want to go ahead and kind of just zoom in on one single cell inside of the liver to visualize what's going on at the cellular level to be able to allow us to convert glucose into a fatty acid and so I'm going to go ahead and scroll the screen here so we can have some more room all right so I'm going to quickly draw an outline of a representative cell and then we'll go ahead and quickly label some important compartments that we want to talk about so the first one is simply the cytoplasm and there's a lot going on in the cytoplasm but we also need to talk about what's going on in another organel inside the cell and that organal is the mitochondria and I'm going to go ahead and draw the kind of two membranes that it has here we're not going to talk about this too much but just because it it is important to remember that this has an inner membrane and an outer membrane remember that the electron transport chain is of course located on the inner membrane and the mitochondria is also within it it's a site of the crep cycle which continues notably to break down glucose following glycolysis which takes place inside of the cytoplasm now since we ultimately want to get down to how extra glucose can be eventually converted into fatty acids we need to actually make sure and remind ourselves how the breakdown of glucose proceeds so as a very very quick review recall that glucose enters our cells from the bloodstream and it enters the metabolic pathway called glycolysis which takes place inside the cytoplasm and the end product of glycolysis is pyruvate and I'll also remind you that for every one molecule of glucose which is a six carbon molecule so 1 2 3 4 5 6 we form two molecules of pyrovate which is a three carbon compound subsequently pyrovate is actively transported across the mitochondrial membrane by specialized carrier proteins located on the membrane and once pyrovate reach is the inside of the mitochondria also known as the inner mitochondrial Matrix there is a enzyme that's only found in the mitochondria called pyrovate dehydrogenase often abbreviated as pghh which oxidizes and removes one carbon from pyrovate so remember we had three carbons and now it turns it into a two carbon molecule called acetal COA now you might recall that this two carbon structure is not done being broken down or oxidized there's still some energy that we can extract from this two carbon molecule and it's extracted inside of the KB cycle so remember that there are many many intermediates along the KB cycle but I only want to mention a couple that will be relevant when we talk about how this breakdown of glucose converges with the synthesis of fatty acids so remember first off that a four carbon molecule called oxy aceto acid acetate which I'm abbreviating here is OAA combines with one molecule of acetyl COA to produce a six carbon molecule now called citrate and citrate continues to be modified oxidized and even broken down a little bit more and it returns to form oxaloacetate which means that we lose two carbons somewhere along the cycle which we do indeed we lose these as two molecules of carbon Caron dioxide so there two carbons of acetyl COA exit as carbon dioxide and we also form a number of reduced electron carrier molecules called nadh and fadh2 which shuttle their electrons from the oxidation process that occurs in the Krab cycle to the electron transfer chain which is located on this inner mitochondrial membrane how convenient right and then from there we can produce ATP using oxidative phosphorilation all right so after that quick Whirlwind tour of the breakdown of glucose you might be wondering where do we convert glucose into fatty acids and it turns out that one of the intermediates of the breakdown of glucose which is acetal COA this two carbon molecule located in the mitochondrial inner Matrix is a precursor for fatty acid synthesis and we're going to go through all of the steps but just to take a step back for a moment the big picture way that I kind of like to think about this is that remember that fatty acids I'm going to go ahead and draw off to the side here remember that most of it is just a repeating carbon hydrogen backbone shown here in this kind of uh line stick model here and so in that sense really we want to basically be able to link together carbon carbon bonds and this acetyl COA is just a pair of carbon carbon bonds that we can ultimately link together now it turns out that we have an interesting situation when it comes to fatty acid synthesis and linking all of these acetyl COA molecules together which is that all of the enzymes necessary for fatty acid synthesis I'm going to say enzymes for fatty acid synthesis are located in the cytoplasm and that's a bit problematic because remember our acetal COA molecule is in the mitochondria now your first thought might be well pyrovate was able to shuttle across using some protein carrier molecules in these membranes into the mitochondria why can't acetal COA do the same going the opposite direction unfortunately for some reason or the other our body has evolved not to have any means to be able to transport this through its mitochondrial membrane there are no protein Transporters or Carrier molecules like we had for pyrovate to be able to essentially shuttle acetal COA in either direction across this mitochondrial membrane but notably our body does have a protein shuttle across this mitochondrial membrane for the molecule citrate and remember that citrate contains acetyl COA of course it also contains this molecule acetyl acetate that combined with it and so let's see what happens when this shuttles across the mitochondrial membrane now once citrate reaches the cytoplasm it turns out that there is an enzyme within the cytoplasm that is able to break citrate up back into oxlo acetate as well as the mo Ule that we're interested in which is of course acetal Co a now when I first learned about this it kind of struck me as a really roundabout way to kind of accomplish what seems like a pretty simple task right which is to get acetal coate into the cytoplasm where the enzymes or fatty acid synthesis can link it together to form a fatty acid but it turns out that there might be a benefit for this citrate shuttle to make fatty acid synthesis perhaps more efficient and so I want to briefly talk about that but I want to erase this just to give us some more room now it turns out that this four carbon molecule oxaloacetate is not going to be used for fatty acid synthesis and so naturally our body says why don't we recycle it and in fact we do have some enzymes that can convert it back to this molecule pyate and notice that pyrovate can essentially once it goes back to the mitochondria it'll be turned into a cetal COA and this entire cycle can continue now although we're not going to go over the detailed mechanism by which Oxo acetate is converted to pyrovate what is important kind of a big picture idea to note here is that we're going from a four carbon to three carbon uh molecule and so we're going to lose a carbon actually as carbon dioxide during this process and simultaneous with this step we're actually oxidizing that particular intermediate and so when we oxidize something we're able to reduce something else and it turns turns out that what we reduce in this case is a molecule of nad+ and so it's reduced to n pH and you may recall that you've seen nadph also as a product of the pentos phosphate pathway and of course we normally think about the pentos phosphate Pathways being the major pathway for the production of nadph but this step also allows us to produce a molecule of pH as well now one of the uses of nadph that you might recall is that because it's associated with these electrons it can serve as a source of reducing power to help with anabolic reactions and remember that anabolic reactions are anything that involve building up a molecule including fatty acid synthesis which is exactly what we're trying to accomplish here so to summarize and just kind of tie up everything that we've just talked about here we've been able to get acetal coate into the cytoplasm where all of the enzymes necessary for fatty acid synthesis are located and this is important because we're going to use acetylcoa multiple acetylcoa kind of a precursor molecule so to say to build up a fatty acid and of course because this is an anabolic reaction we're going to need some ATP somewhere along the way and we're also going to need some reducing power to kind of help form all of those carb carbon bonds and we can get that using nadph of course nadph can be supplied by the pentos phosphate pathway but conveniently perhaps by using the citrate shuttle we're also able to produce a molecule of nadph from the conversion of oxlo acetate into pyrovate in the next video we'll pick up right here in the cytoplasm to talk about how this conversion from a cetal COA into a fatty acid occurs