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Fatty Acid Synthesis - Part I

1D: What are the sources of fatty acids in the blood stream? Where are fatty acids synthesized? How are the synthesized? Created by Jasmine Rana.
Video transcript
now the ultimate goal in fat metabolism means to be able to deliver some try a so glycerides gender green here's th e which remember is the chemical name for a fat molecule or free fatty acids which I believe it here is FF a witch if your call are thee 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 is a capillary bed and it's important that they reach the capillary beds because it's at this point where they can diffuse to the surrounding tissues such as muscle or hard tissue for example where they can be taken up by these tissues and oxidized to obtain cellular energy in the form of ATP now you want to remind you that there are three main sources of these triethyl 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 started 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 whatever so he was the fact that ultimately reaches their bloodstream is directly from our diet may recall that our small intestine digest our food and packages the fat molecules the tri acyl glitterize into protein carrier molecules called kylo microns which travel through the lymphatic circulation but eventually empty into our bloodstream where they can enter capillary beds now the second way that we can get some fat into her bloodstream is directly from adipose cells so recall that adipose cells are specialized cells inside of our body that can store large amounts of fat and so that's kind of wanted to run here in these yellow circles within these cells these large fatty droplets and several hours after a meal when your hormone insulin begins to drop inside of your body and other hormones such as glucagon began to rise they signal these ads host cells to release free fatty acids directly into the bloodstream and recall that free fatty acids are very hydrophobic so they kind of surf essentially they kind of attached themselves on to albumin molecules which is a special type of protein that's always found inside of our bloodstream now the third way that we can get some that into our bloodstream is by synthesizing it directly inside of the liver which I've kind of draw 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 try acyl glyceride molecules and packages them together with cholesterol another hydrophobic molecule into another specialized protein carrier molecule like chylomicrons but this one has a slightly different name is called very low density lipoprotein or vldl short and this of course is sent off to the bloodstream where it will eventually reach capillary beds and be taken up by surrounding tissues even perhaps adipose cells which might store it up for later use so now that we've gone over 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 i'm going to go ahead and scroll the screen here so we can have some more room alright 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 organelle inside the cell and that organelle 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 chains of course located on the inner membrane and the mitochondria is also within it it's the site of the kreb 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 there's a very very quick review recall that glucose enters our cells from the blood stream 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 that one two three four five six we form two molecules of pyruvate which is a three carbon compound subsequently pyruvate is actively transported across the mitochondrial membrane by specialized carrier proteins located on the membrane and once pyruvate reaches the inside of the my country also known as the inner mitochondrial matrix there is the enzyme that's only found in the mitochondria called pyruvate d hydrogenase often abbreviated as PDF which oxidizes and removes one carbon from pyruvate so remember we had three carbons and now it turns it into a two carbon molecule called acetyl co a now you might recall that this to carbon structure is not done being broken down or oxidized there's still some energy that we can extract from this to carbon molecule and it's extracted inside of the kreb cycle so remember that there are many many intermediates along the kreb 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 4-carbon molecule called ox low acetoacetate which I'm abbreviating here is 0 AAA combined with one molecule of acetyl co way to produce a six carbon molecule now called it rate and it rate 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 carbon somewhere along this cycle which we do indeed we lose these as two molecules of carbon dioxide so there's two carbons of acetyl co a exit is 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 kreb 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 phosphorylation alright 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 acetyl co atis to carbon molecule located in the mitochondrial inner matrix is 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 gonna go ahead and draft to decide you remember that most of it is just a repeating carbon-hydrogen backbone shown here as kind of a 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 co a is just a pair of carbon-carbon bonds that we can ultimately linked together now it turns out that we have an interesting situation when it comes to fatty acid synthesis and linking all these acetylcholine molecules together which is that all of the enzymes necessary for fatty acid synthesis essay enzymes for fatty acid synthesis are located in the cytoplasm and that's a bit problematic because remember our acetyl co a molecule is in the mitochondria now your first thought might be well pyruvate was able to shuttle across using some protein carrier molecules in these membranes into the mitochondria why cant acetyl co way to 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 the mitochondrial membrane there are no protein transporters or carrier molecules like we have a pyruvate to be able to essentially shuttle acetyl co in either direction across this mitochondrial membrane but notably our body def have a protein shuttle across this mitochondrial membrane for the molecule citrate and remember that fit rate contains a fetal co e of course that 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 it rate reaches the cytoplasm it turns out that there is an enzyme within the cytoplasm that is able to break it rate up back in to oxaloacetate as well as the molecule that were interested in which is of course a seagull co a now when i first learned about the 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 a fetal kawai 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 the fifth trait 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 4-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 pyruvate and notice that pyruvate can essentially once it goes back to the mitochondria it will be turned into acetyl co a and this entire cycle can continue now although we're not going to go over the detailed mechanism by which oxaloacetate is converted to pyruvate what is important kind of a big picture idea to note here is that we're going from a four-carbon to 3 carbon 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 were able to reduce something else and it turns out that what we reduce in this case is a molecule of an 80 plus and so it's reduced to an a/d ph and you may recall that you've seen any dph also as a product of the pentose phosphate pathway and of course we normally think about the pentose phosphate pathway is being the major pathway for the production of nadph but this step also allows us to produce a molecule of nadph as well now one of the uses of nadph that you might recall is that because its associated with these electrons it can serve as a source reducing power to help with anabolic reactions and remember that anabolic reactions are anything that involved 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 tired of everything that we just talked about here we've been able to get a little kuwait 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 the acetyl co a multiple fetal co a 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 for all of those carbon-carbon bonds and we can get that using any g ph of course nadph can be supplied by the pentose phosphate pathway but conveniently perhaps by using this straight shuttle were also able to produce a molecule of nadph from the conversion of oxaloacetate into pyruvate in the next video will pick up right here in the cytoplasm to talk about how this conversion from acetyl co a into a fatty acid occurs