Gastrointestinal | Liver Metabolism, Protein Synthesis & Storage

I mean interns in this video we are gonna talk about the physiology of the liver we have a lot to talk about so let's go ahead and get started alright guys so the first place we're gonna start off with is the liver functionally in metabolism as you guys know we've talked about all the metabolic pathways that we're gonna kind of briefly briefly cover and our metabolism playlist so if you guys want to know about those Pathways in more detail go check that out in that playlist what I want to do is because the liver has

so many pathways that it's involved in I want to break it down into two individual pathways the Fed stayed in the fasting state I think that's one of the best ways because it makes it a lot easier it makes it more understandable and again we're not gonna go through this in super super detail I just want to get the basic components of this and help us to Understand what the liver can do the liver is so amazing um I had a biochemistry professor once telling me that if you want to tell someone how much you

love them you say I love you with all my liver because that sucker can do so many things and by the time we're done with this video you guys will truly see that it is a magnificent Oregon all right so let's first off start off in the Fed state with looking at carbohydrates so as you know the Portal blood is gonna be bringing a lot of nutrient-rich blood from the gastrointestinal tract so one of those molecules that we're gonna see a lot of being brought into our liver cells is glucose you know we bring glucose

into our liver cells through blood transporters particularly blood to transporters now what can we do with that glucose once we bring it into the cell well I want you to remember that there is gonna be at least four Significant pathways okay one thing is we're in the fed state we have a high amounts of glucose being brought into our circulation so because of that there's gonna be a very very important hormone that's regulating all of these pathways that we're gonna see in the fed state that significant hormone that I want you guys to remember that

is driving all of these pathways that we're gonna see in the insulin I mean in the Fed seat is going to be insulin so as You know the pancreatic beta cells are going to secrete insulin and insulin is going to control a lot of different pathways within the liver now one of the things that happens is glucose is brought in to the cell via the glut to transporters once it's brought in we can take that glucose and convert it into a storage form okay and that is going to be called glycogen so that's one significant

thing that we should know so one pathway that We really should understand here is going to be glycol Genesis let's do that in pink here so this is going to be one pathway here that is really important that it's going to be glyco Genesis another pathway that's super super important is going to be the hexose monophosphate shunt or as you guys know at the pentose phosphate pathway so if you guys remember it glucose when we took it through the pentose phosphate pathway it led to the formation of Ribose 5-phosphate but that's not the significant thing

that I want you guys to remember there was particular molecules that were actually developed during this process and those specific molecules that we generated is we took this molecule called nad p+ and generated what's called in adp h's if you guys remember this was important in fatty acid synthesis it's important in nucleotide metabolism it's important in antioxidant reactions trying to Regenerate glutathione into its reduced form really really important ok so that's the second pathway that i want you guys to understand is it's going to also increase the activity of the pentose phosphate pathway another thing

is is insulin loves to catalyze the katate to catabolized glucose into the forms that we can utilize for energy so what is that we can take glucose as you guys know and if you know we can break down glucose into two components you Form what's called GA 3 P which is glyceraldehyde 3-phosphate and you get another molecule called dihydroxyacetone phosphate now as you guys know these guys can isomerize into one another but the significant thing is is that these guys eventually end up forming pyruvate two of them okay and then that pyruvate that we actually

generate can be converted into what's called a cetyl Co a and as you guys know acetyl co a will go through the Krebs Cycle or the tricarboxylic acid cycle will put TCA cycle for tricarboxylic acid cycle and again do remember it's also called the Krebs cycle and then from this we generate tons and tons of nadh and fadh2 s and what these suckers do is they take these badboys to the electron transport chain and they generate ATP all right so that is the significance that I want you guys to understand here so one pathway is

were forming glycogen filled glyco Genesis 2 Was performing ribose 5-phosphate but the significant thing is that it were generating a lot of NADPH is via the pentose phosphate pathway and the third thing is we're going to catalyze the oxidation of glucose into ATP formation so that's a significant thing now here's the thing - one more thing that we should realize glucose is in such high levels so sometimes our liver will perform the glyco genesis it'll form the pentose phosphate pathway and i'll Catalyze the oxidation of glucose into forming ATP but guess what happens sometimes you

form a lot of these acetyl co a molecules a lot of these bad boys okay and if you guys remember we said that whenever there's excessively large amounts of acetyl co a it inhibits the particular enzyme that converts citrate right you have what's called citrate and then isocitrate and then alpha ketoglutarate well the citrate is then cannot going to be able to convert it Into isocitrate so if you guys remember there was an enzyme that called citrate lyase that broke down into so here look there's a molecule called citrate but because there's excessively high levels

of acetyl co a the citrate can't be converted into isocitrate so what it does is there's an enzyme called citrate lyase and what that does is it breaks this guy down into two components one is called oxaloacetate OAA And the other one is called acetyl co a and if you guys remember the acetyl co way was then converted into what's called now an isle Co a and that now a knock away is what was made for fatty acids here I won't be lazy I'll actually write out here fatty acids fatty acids so now we understand

that there's actually going to be two things here one is if there's excessively high levels of glucose it'll lead to excessively high Levels of acetyl co a that will have a lot of krebs cycle activity a lot of NADH is a lot of fadh2s a lot of ATP that the krebs cycle is going to be inhibited because of that then citrate is converted into acetyl co a and then into malonyl co 8 and then into fatty acids so this is a fourth thing that is important it can also lead to fatty acid synthesis and as

you guys know the liver is one of the organs that can generate glycerol so we can also take this Dihydroxyacetone phosphate and we can actually convert this bad boy into glycerol and as you guys know we can take the glycerol and the fatty acids and guess what we can do with these bad boys if we take glycerol and the fatty acids we can make what's called tri glycerides I'm going to denote that is try a steel glycerol but it's the same thing as triglycerides okay so again that is the significant part here what else is

coming to the actual Liver besides glucose this is the big one but it also is regulating amino acids so you know amino acids are brought in let's do these bad boys and a baby blue so now amino acids are brought into the cell and then when they're brought into the cell they're actually brought in via what's called a sodium dependent co-transport okay so sodium will be brought into the cell along with the amino acids via KHOU transport the main Thing with the amino acids is is these guys are going to be designed to form one

really important thing there is some other things that they're going to do but I want you guys to remember the main thing within the liver it's going to lead to the genesis of proteins this is the really really important thing that I want you guys to remember here is amino acids are going to lead to the synthesis of proteins now if there is excessively high levels Of amino acids and we aren't we actually have formed all of our proteins sometimes what can happen if some of these amino acids can be converted into what's called acetyl

co a and that acetyl co a can do what can lead to the formation of citrate because it's not gonna go through the krebs cycle right now some of it might go through but we're gonna assume that a lot of it's going into citrate and then into acetyl co a Then to malonyl-coa and then into fatty acids and then if we take those fatty acids and combine it with glycerol what can we get triglyceride so that's important to remember okay so two things I want you guys to remember for this guy for the amino acids

one is there's going to be primarily the synthesis of proteins and the second thing is that if the amino acid levels are really really high we can take and convert it into a cetyl Co a or other keto acid Intermediates and lead to the formation of fatty acids and then the fatty acids can combine with the glycerol and form triglycerides that leads us to the next guy okay what about fats now you know the liver it actually is receiving a lot of its fat and cholesterol substances from these little little structures called chylomicrons I know

you guys have talked we've talked about this primarily in the lipoprotein metabolism all right so now If you guys remember we had these molecules called Kyllo microns these were important because they were taking a lot of the cholesterol so what are they carrying with them the primarily carrying a lot of triglycerides I'm gonna put ta G that's the big thing that they're carrying a lot of and they're carrying a decent amount of cholesterol as well as with other substances but the significant thing is that we know that it's going to be bringing with the Triglycerides

now when it takes it to the liver there is particular enzymes that will take and break down the triglycerides into fatty acids and glycerol so what we can get from this is we can get some free fatty acids and what will happen is these free fatty acids will lead to we can take and incorporate that into the formation of triglycerides what else well what did the Frick is this cholesterol going to be doing We need to do something with this bad boy so cholesterol in this time period we can take this cholesterol and it has

three fates okay one fate is we're gonna lead to it lead to the formation of cholesterol esters so let's take this guy and let's say we make cholesterol esters if you guys remember this is the storage form of cholesterol so this is the storage form and we use a particular enzyme to do this called a cat a co co a acetyl transferase all we're doing is We're adding a different acyl group or cetyl group onto this cholesterol molecule another thing and we'll talk about this in another video is we use this cytochrome system particularly cyp

7e 1 there's this enzyme called 7 alpha hydroxylase and there's another one called 12 alpha hydroxylase which are really important that take and add on hydroxyl groups onto cholesterol and convert these badboys into bile acids again we'll talk about This in more detail when we talk about the biliary system and another thing that we can do with the cholesterol let's bring it up one more is we can take and incorporate these bad boys into something else let's say I take the cholesterol that I brought right from my chylomicrons I take the triglycerides that I got

from synthesizing it from glucose or from amino acids and I take those triglycerides and this cholesterol that I have here say I take this Cholesterol and guess what I'm gonna do with these bad boys I'm gonna combine them together and I'm gonna secrete this out of the cell get the guess what this molecule here is called this is actually bring it let's keep it inside the cell here so I'm gonna take this triglycerides I'm gonna take the cholesterol I'm going to combine these bad boys together and I'm gonna get what's called VL DL molecules and

if you guys remember these VL deals we can put These out into the actual circulation and distribute a lot of the actual cholesterol on the triglycerides to the fat tissue the muscle tissue and if you guys remember the VLDL will actually return so to lead it actually lead go to the adipose tissue go to the muscle tissue and then afterwards it'll come back in the form of AI DL alright and some of that idea will be taken up by the liver some of the IDL will then be converted into LDL And we know that that

LDL will actually take that cholesterol it's a lot of different peripheral tissue cells and the remaining you'll be brought back to the liver and then there's one more molecule we actually seek read out HDL and that HDL will take and pick up cholesterol from the peripheral tissues and bring a lot of that cholesterol back to the liver so that's important to remember okay so one of the big things that I want you remember about the fat Metabolism one thing because I want you to remember that chylomicrons are bringing exogenous forms of triglycerides and cholesterol to

the liver the triglycerides I want you guys to remember is being actually we can have free fatty acids being formed we can take and convert that back into triglycerides by combining with glycerol we also have the cholesterol coming from the chylomicrons that can be converted into bile acids we can take and convert Into a storage form of cholesterol or we can incorporate it into lipoproteins particularly VLDL that VLDL will then do what go to the adipose tissue go to the muscle tissue drop it off and convert it into ideal ideal some of that can come

back to the liver and drop off the cholesterol some of it will become LDL then the LDL we'll take that cholesterol drop it off into various tissues which can use it for steroidal Genesis but unfortunately as you guys know some of This LDL can also deposit some of the cholesterol and lead to atherosclerosis if oxidized particles occur and then we know that HDL is also another really important one that goes to these peripheral tissues and pulls a lot of that cholesterol off of the vessel walls right and then returns the remaining cholesterol back to the

liver so that's important to remember that so that is the second thing that we should also know here okay now we've gotten a really Good understanding of what's happening in the actual fed state with glucose we know what's happening in the basis of amino acids and we know the basis that is happening with the molecules now what I want to do is I want to take in the next step and I want to see how this is actually how these metabolism occurring in the liver during the fasting state all right so now we're gonna do

a look at the metabolism that is occurring in the liver in the fasting State so now we're looking at the opposite here we're looking at it's been a while since we've eaten our glucose levels in the blood are starting to drop and there's a particular hormone that's being released in response to these low blood glucose levels and that hormone is going to be glucagon okay goo ganas if you guys remember released from the pancreatic alpha cells there's other hormones that are also released you know you have cortisol that could be acting In this time period

you have another one that being growth hormone other ones could be like epinephrine there's even neuro epinephrine a bunch of these guys even thyroid hormone if you want to throw that bad boy in there - t3 and t4 so a lot of these guys are going to be driving a lot of the fasting state processes so what's happening here in the fasting state here's what I want you guys to remember let's go back and let's look at this with respect to Glucose let's look at it with amino acids and let's look at this with respect

to fats so the first thing is is now our blood glucose levels are low that's the stimulus here what was the stimulus here the stimulus was low blood glucose levels okay our goal in the fasting state is to increase the blood glucose levels so one thing that we're going to want to do is is we're gonna want to be able to break down that reserve of glycogen into glucose and put That into the blood so that's one of the definite things that we're gonna want to do here so let's say we take this glycogen that

we had stored here and now what I'm gonna do is I'm gonna break this down into glucose so this is called glycogenolysis so this is one important pathway here this is one big thing here okay glycogenolysis what else okay well we did glycogen and Isis let's do something else let's do the opposite of glycolysis Let's do gluconeogenesis so you know why this is so cool if we take amino acids so we can take amino acids and we can convert these amino acids via what's called transamination we've talked a lot about this we can convert this

into glucose so that's one really important thing to remember is we can take these amino acids and we can undergo what's called a transamination process where we convert into different keto acids particularly pyruvate and that pyruvate Could lead to the formation of glucose so that's one another pathway that can happen another thing is you know um glycerol we're actually glycerol is actually a product of light poly pollicis so we can do here is we can take the glycerol that we can get from lipolysis we can take that glycerol that we can get from the lipolysis

that it's carrying in the adipose tissue or in the muscle tissue or even liver tissue and we take that glycerol and we can convert That into glucose so that's another pathway that is occurring here so that's the third thing another situation is your muscles they release a lot of lactic acid and a lot of that lactic acid as it builds up we can actually take that lactic acid and use it for good we can take that lactic acid and convert that into glucose that is the fourth thing and all of these processes are gonna be

under what's called the gluconeogenesis pathway right so Gluconeogenesis is taking non carbohydrate molecules and converting them into glucose so we take amino acids glycerol lactic acid if you wanna throw one more in there there's also odd chain fatty acids we can do that but they have a minor contribution to the blood glucose levels okay so that's the big thing there now something else that we should remember when we take these amino acids and we try to convert them into glucose the process of amino acid Catabolism can push out something so you know during that process

when we break down we take the amino acid and we try to convert it into glucose we generate what's called glutamate okay you know you get this usually as a product of transamination that glutamate is then going to do something in the liver you know glutamate it can actually rip off an ammonia molecule off of it there's a glutamate dehydrogenase enzyme That works in this pathway and then what will happen is that glutamate when it rips off the actual amine group it converts this guy into alpha keto glue to rate which is a krebs cycle

intermediate right well guess what happens with that ammonia this is a super toxic molecule because it is so toxic what we can do is we can send this bad boy through a cyclic pathway called the urea cycle the urea cycle and in the areia cycle we use particular enzymes to Take and push out of this molecule called urea and the you know urea urea is less toxic and it's actually we're able to send this to a particular organ in the body you know the kidneys the kidneys can actually take up that urea and excrete that

urea right so look we're gonna take in pipi that sucker out so now what we're gonna see in the urine is we might see a lot of urea okay that's one important thing this accounts for the Ammonia going through the urea cycle and producing a urea accounts for 95% of the ammonia metabolism but guess what there's another guy you see this this ammonia molecule he can go right back in by not to glutamate so he can take and he combined right on to glutamate and when these two guys bind together let's actually do this like

this these guys when formed they can lead to a molecule called glutamine this is an important one to remember because there is an Enzyme that I should mention that drives this process and this is called I mean synthetase so glutamine synthetase is the enzyme driving this process and it's converting the glutamate to glutamine which is gonna pick up that ammonia molecule and guess what we can do the glutamine we can send this bad boy to the kidneys and excrete out the glutamine into the urine and this accounts for 5% so the formation of glutamine accounts

for 5% of the ammonia Handling there okay so that's one important thing that we should remember as a result of amino acid metabolism particularly in the fasting state when the amino acids undergo the transamination process and are converted into glucose via gluconeogenesis or we can take the amino acids you'll see and not just convert into glucose but we can utilize it for energy during that process we generate what's called glutamate and then glutamate an ammonium Molecule we get an ammonia molecule pulled off of it and that's called oxidative deamination that leads to the formation of

alpha keto glue to rate that ammonia molecule is two pathways one is it can be converted to glutamine which can be or needed out only accounts for 5% or it can go through the urea cycle and form urea and BP peed out reason why this is important because if ammonia is not actually undergoing this cycling process ammonia levels can build Up in the blood why is that dangerous because it can lead to a lot of problems with in your central nervous system particularly what's called a paddock encephalopathy which can happen whenever there is certain situations

like hepatitis or cirrhosis or wilson's disease or maybe hemochromatosis infections of the liver whatever might be that's damaging the liver and decreasing its function it can cause problems with this ammonia handling okay So so far we know that we're doing glyco general lysis gluco neo Genesis glutamine synthesis the urea cycle something else that we should understand I already said it already is some of these amino acids they don't just have to undergo this gluconeogenesis some of the amino acids can actually be converted into it might actually be converted into for example let's say I take

these amino acids and I send them into the TCA cycle Ok the TCA cycle and then from here we can take these guys send it to the electron transport chain and lead to the formation of ATP if necessary ok so there's another thing that we should understand here is that we can take amino acids if we need to and we can send them into the tricarboxylic acid cycle and generate some energy from those molecules as well so they don't always have to go into the formation of glucose now what about the fad this is a

Really really important one so if we take the triglycerides because our liver can actually have you know stores we can have triglycerides ok so let's say t AG the liver can break down the triglycerides into two components one is obviously called glycerol and we know where that molecule went we know that it went to form glucose another thing is the triglycerides can lead to the formation of what's called fatty acids now the fatty acids can undergo this Process where they have what's called beta oxidation and that beta oxidation will take the fatty acids and convert

into what's called acetyl co a okay now this acetyl co a can take and go through the Krebs cycle right or the TCA cycle and then from here we might take some of the NADH s and the fadh2 send them to the electron transport chain and make some ATP but guess what because there sometimes there can be a lot of fatty acid metabolism and again what does this Process here called it's called beta oxidation sometimes in the liver if we have a fasting state for a long period of time the acetyl co a molecules can

build up why is that important because these acetylcholine molecules if they build up they can be converted into these special little molecules called ketone bodies okay and the ketone bodies there's actually of two types two different flavors one is Called a Seto acetate and the other one is called beta hydroxy butyrate technically there is another one if you really want to be specific there's even acetone but really this one is going to be breathed out or exhaled okay so that is another thing that we should remember can happen in the fasting state so so far

what do we have glycogenolysis gluconeogenesis we have glutamine synthesis we have the urea cycle and happening we even have Lipolysis that can be occurring here so we can have lipolysis that's the seventh part and we can have beta oxidation and if there's excessively high levels of acetyl co a we can take and convert that into ketone bodies so that is the significance that we should understand here with the liver that is happening what's happening in the fasting state okay so now what I want to do is we got a good chunk of the metabolism down

again if you guys really want a more in Detail look at this stuff we covered this in our metabolism playlist so go there check out all those videos I just wanted to get a basic little thing here for how the livers involved in metabolism alright guys so now we're gonna talk about actually let me flip these guys here I think it's better if we talk about protein factory first because I think it's gonna make more sense it's gonna flow better anyway here so let's go ahead and switch these And let's make this one here let's

make this the protein factory let's cover this is the protein factory because you know deliver us so many proteins that it can set the size you guys will see it's an unbelievable and then we'll talk about storage last okay so protein factory obviously you know that the liver has the ability to make tons and tons and tons of proteins now here's the thing what I want us to look at this in is I want us to look at this in a bunch Of different ways all right so this guy makes tons tons and tons of

protein so what are some of the proteins here out of all of these I really guys don't forget this one this is the most significant protein that the liver makes and this is called albumin you guys already know that I'll boom it accounts for like 60% of your plasma proteins now how does it what is the function of albumin how boomin maintains your osmotic pressure so for Example let's say I had a capillary here so here is a little capillary you know that in the capillary there's hydrostatic pressure pressure that pushes things out of the

actual capillary like different solutes and water and electrolytes and then there's another pressure which tries to keep the water inside of the actual capillary how boomin is playing a role in this and the reason why that's important is imagine here imagine here's the tissue cells Right so here's a couple tissue cells in between the blood and the tissues is the interstitial fluid right now let's imagine here for a second that job human levels were low what would happen a lot of the water in this area would accumulate a lot and then that would lead to

swelling of the interstitial that's called edema that's why human is so so important and we should really understand this guy also when people have a long term or severe injury to the Liver like due to hepatitis or cirrhosis whatever the etiology might be one of the long-term signs that there is liver damage is the albumin production starts decreasing as well as you'll see in other proteins that they make is they make a lot of clotting factors so what's called their prothrombin time the time it takes for them to clot basically that's also a lot longer

okay so that's the real important protein that want you guys to remember here other ones it Makes a bunch of different proteins and these guys are called your globulin there's alpha and there's beta-globulin s' now out of these guys these guys are transport proteins they're the ones that transport a lot of different it's soluble substances like maybe steroid hormones or steroid based substances or things that like trace minerals like copper and iron and stuff like that okay so for example just to name a few of these guys let's say I Have one I already mentioned

copper there's a protein that transports that it's called ceruloplasmin okay super super important it transports copper reason why this is important is is that you know that there is a disease called Wilson's disease pretty rare but what happens is its copper overload disorder there's a protein called ATP so atp7b and it's what's responsible for taking the copper and combining it onto the ceruloplasmin that protein is Actually defective then the copper levels will actually start increasing and lead to a lot of free radical reactions so that guy's super important that we should understand also remember that

the copper is also secreted into our biliary system two other ones we also mentioned iron there's another protein called transferrin and transferrin is responsible for transporting hyerin he takes the iron and delivers it to the various different Tissues one is it could be the bone marrow because that's needed for erythropoiesis and it takes it to the liver and the liver will actually store that iron in the form of ferritin or if we have a lot of ferritin that can polymerize inform hemosiderin okay other ones haptoglobin haptoglobin sometimes you know when there is hemolysis of our

red blood cells the breaking of the red blood cells hemoglobin can be released and some of that hemoglobin we need to Bind it onto haptoglobin okay scuzz hemoglobin is actually a pretty toxic inside of our actual blood on its own so that's important too other ones let's say that we have oh oh we have what's called retinol binding protein so retinol binding protein this guys super important he actually you'll see later when we talk about the storage function of the liver the retinol binding protein actually binds on to retinol and Transports the retinol to various

different tissues what is the what is one of the big tissues that retinol is needed in in the eyes it's needed for the actual dim light vision right so that's important it's also utilized in our skin it also transports different types of steroid hormones for example cortisol cortisol is actually transported via what's called trans Courtin and then thyroid hormone thyroid hormone is transporting the formulas Called thyroxine binding globulin s-- so tons and tons of proteins I'm not going to keep going through all of these bad boys but I just want you guys to get the

idea that the alpha and beta globulin are designed to be able to act as carrier proteins to transport substances that are lipid soluble they're hydrophobic in other words or that can be super dangerous and can lead to a lot of free radicals specifically the iron in the copper these guys can lead to a Lot of dangerous reactions particularly if you guys know we'll talk about it later the Fenton reactions pretty dangerous stuff okay so the transporting steroid based substances or ions or metals okay well some other proteins that the liver makes besides these badboys it

also is responsible for making different types of clotting proteins and anti clotting proteins so for example let's say I have clotting proteins you Guys know a lot of these there's so many of them right so but here's the ones that I want you guys to remember the big big big ones factor - okay factor seven factor 9 factor 10 protein C and protein s the reason why I want you guys remember these is these soccers right here are vitamin K dependent so in order for these proteins to become active they need to have vitamin K

okay so that's some really really important ones so he makes a lot of different clotting Proteins another one that's really important here and the clotting cascade is it also makes what's called fibrinogen okay fibrinogen which is actually factor one that's important for the fibrin mesh as you guys remember fibrinogen was acted on by factor you know there's actually thrombin or factor-2 and what they did is that converted fibrinogen into fibrin and then fibrin was responsible for forming That fibrin mesh that anchored down that platelet plug and if you remember factor 13 actually takes in cross

links to fibrin strands to really anchor down that fibrin mesh so that's really important as a side to oppose the clotting it also likes to keep a nice little balance it also makes these anti clotting proteins so if I hear let's word like that anti clotting proteins so what are some of these bad boys that it makes it makes what's called you guys Should know this one plasminogen plasminogen super important one if you guys remember plasminogen is acted on by an enzyme called TPA all right whenever someone has an acute thrombus or something like that

whenever they might have a clot we give them TPA why because TPA converts plasminogen to plasmin and what it was plasmons job remember we represented this as like a nice little pac-man like enzyme and what was it breaking down it was breaking down look At this the fibrin and it was spitting it out in the form of fibrinogen and sometimes you might even see it in the form of what's called d-dimer's sometimes that's why somebody has an elevated d-dimer they might have actually had some type of clot right so that's really important he makes plasminogen

what's another really important one that he makes another really important guys called anti thrombin 3 if you guys remember Antithrombin 3 binds with heparin sulfate on side bar endothelium and antithrombin 3 was responsible for degrading particular types of clotting factors and what were some of those out of all of these if you guys remember just remember that it inhibits or deactivates factor 2 which is thrombin it also deactivates factor 9 and it also deactivates factor 10 so that was some of the things that you guys should remember Here okay so we got clotting proteins anti

clotting proteins water some of the other ones here's what I love about this guy he also can make hormones so what are some of these hormones this is what's super interesting most people don't know most people forget about this when they think about the liver nothing's really interesting about the liver and I go off on tangents a little bit but you know the liver is actually the site of red blood cell production And the fetus so it actually starts off in the primitive yolk sac and then the liver carries out the erythropoietin process till about

the 32nd week of gestation when the bone marrow takes over but there's another thing that also controls it actually makes a particular hormone called thrombo poem in thrombopoietin if you guys remember we talked about it very very briefly there's what's called the myeloid stem cell if you guys remember that right and What it does is thrombopoietin actually leads to the platelet synthesis so platelet formation if you guys remember we said that thrombopoietin will take a pluripotent stem cell well you have what's called pluripotent stem so our hemocytoblast converts it into a myeloid stem cell and

then thrombopoietin will stimulate that myeloid stem cell to turn into a maybe carry a blast then it goes to a pro megakaryocytes and then a megakaryocytes and then the mega carry Start start shedding platelets and then these plays are important for actually for helping to form blood clots right for plugging different holes inside of the blood vessels another one another hormone is called insulin-like growth factor-1 we talked about this in the growth hormone video okay and what does this guy do if you guys remember it acted on muscles it acted on bones it acted on

cartilage and it increased the protein Synthesis in these guys so it helped to be able to increase the muscle size and muscle density it helped to be able to increase the endochondral ossification it also helped to increase interstitial growth and collagen type 1 production so that's an important one what's another one this guy is so doing cool NGO tents Inogen and if you guys remember angiotensinogen is acted on by Renan which is secreted by the jg cells In the kidney that converts angiotensinogen to angiotensin one and then angiotensin one is acted on by ACE angiotensin

converting enzyme in the lungs and eventually that's converted into angio tense in two and if you guys remember angiotensin 2 super important and involves an 88 release aldosterone release vasoconstriction of our blood vessels all the design to increase the blood pressure so we know it has albumin alpha beta globulin clotting proteins Anti clotting proteins hormones that's another really important time and I want to finish off with here let's do one more really big one and that's immune okay it also makes a lot of different immune proteins now out of these there's there's at least two

that you should remember okay just let's do it let's just do two so out of these one is the complement proteins we talked about this in our immune ology playlist right there's complan protein C 1 to C 9 and They're involved in the act the alternative pathway the classical pathway and even they're also involved in the lectin pathway what was the significance so the big big significance with these guys they're involved in what's called opsonization what does that mean okay let's imagine here I have a piece of bread yeah but then you take some Nutella

mmm rub that all across that bad boy what Does it do it makes it a lot tastier that's what these compliment proteins are doing they're increasing the tastiness of the bacteria or pathogens which enhances the phagocytosis process and you also remember that there I can act as chemotactic agent C 3 a and C 5 a okay one more is C reactive peptide please remember this one C reactive PAP tied so C reactive peptide is important because this guy is one let's say you take a blood panel you test Their blood and you see that they

have elevated c-reactive peptide levels what does that mean that means that the person has active inflammation it's a sign of that right there's a hormone interleukin called interleukin 6 as well as interleukin 1 and tumeric rhotic factor alpha that can be released whenever there's inflammation by macrophages and it stimulates the liver to produce C reactive peptide and that's an actually an inflammation marker but What C reactive peptides do is they act as obstinance so they actually activate the complement system and that is important so if you can see here look at this this is just

unbelievable what the actual liver can do and this doesn't include all of them that's what makes it even more amazing okay so this is just a few of the proteins that the liver is making that I want us to kind of just get a basic view of oh one more one more that I completely forgot about it Shouldn't forget this one is it's also responsible for making these things called able proteins Depot proteins we talked about these a lot in lipid metabolism that lipoprotein metabolism and if you guys remember it was a po Hey a

PO be a possi and a po e so we talked a lot about April a 1b 100 B 48 c2 in April e so it synthesizes a lot of those April proteins which is significant and our lipoprotein metabolism okay so that covers the just of the protein factory Let's come over here and let's hit it home with the storage function alright so to finish it all up guys we're gonna talk about the storage function of the liver okay so here's what I want you guys remember it stores fat soluble vitamins primarily ad E and K

as well as vitamin b12 okay and we'll talk about its storage of trace minerals like copper and iron okay so let's start off first with the vitamin so obviously a lot of all of These vitamins so here let's imagine here you have what's called your Chi low microns and the chylomicrons if you guys remember they were transporting triglycerides cholesterol phospholipids as well as vitamins a d e in k now these chylomicrons you know they go through the lymphatic system and into the circulation and then they get taken to the liver now let's see what it

does with each one of these guys I don't want to go crazy over all of them I want to Focus on two primarily so let's do those two important ones that I want to really focus on that's vitamin D and vitamin K so a lot of the vitamin D can be brought via the diet but here's the other one that I want to talk about a significant amount of vitamin D is actually coming from our skin your skin has a cholesterol molecule and it called 7d hydro cholesterol so what is this molecule called it's called

7d hydro cholesterol holy frack that's a long Name right so when sunlight let's say photons look at this there's some photons some photons are hitting the skin it actually can take the 7d hydro cholesterol and convert it into another molecule and what it does is it converts into what's called cholecalciferol I'm not gonna spell it out that's too crazy CCF now this cholecalciferol will then go to the liver okay now the livers job in this is it takes let's say here's the liver here's The liver here's a little baby liver there's your falciform ligament it

has an enzyme called 25 hydroxy 25 hydroxylase so we're just gonna put here this guy over here there's an enzyme called 25 hydroxylase and what that does it puts a hydroxyl on a 25th carbon of this cholesterol derivative and this is now going to be called 25 hydroxy cholecalciferol now from here it'll then go to another organ it'll go to your kidneys okay so now it's just drawing a Little baby kidney let's get this little guy over here no baby but baby kid me okay now I have a little baby kidney has a particular enzyme

in it and this is called one hydroxylase one hydroxylase what that one hydroxylase does is what do you think it does it puts a hydroxyl group on the one carbon of this cholecalciferol which is this cholesterol derivative and converts it into 1 comma 25 dihydroxy Cholecalciferol holy crap now what is this guy this is the active form of the vitamin D that's the active form now what this does is this 1 comma 25 hydroxy cholecalciferol is he goes to your GI tract so for example he'll come here to your GI tract and when he comes

to your GI tract it increases your calcium absorption it activates particular genes that increase the synthesis of calcium binding proteins and that's gonna lead to increase Calcium absorption pretty cool huh all right so that's the one there so this one right here is reciprocal for your vitamin D okay so that's its function there what's another thing that it can do another thing is we said we were gonna focus on vitamin K okay so what does vitamin K here let's actually take care this baby blue here so now again here's gonna be the next one vitamin

K well vitamin K here's what I want you guys to remember super super Important we already talked about in certain clotting proteins so what happens is here's the cool thing with the vitamin K vitamin K comes in two forms there's what's called the oxidized form which is usually in the form of an epoxy and then there's another one called the vitamin K that's in the reduced form so now this is in the reduced form and then these guys can go back and forth so we can take this vitamin K and the oxidized form convert Into

vitamin K in the reduced form now there's an enzyme here let's do this guy here in red this is called that converts the oxidized form into the reduced form and this is called vitamin K app oxide reductase now why is that important you know there's a drug called warfarin they use it in trying to treat patients who have you know increasing incidences of clotting or maybe even atrial fibrillation they use this as a blood thinner because what it Does is it inhibits the vitamin K Epoque side reductase if that happens vitamin K in the oxidized

form can't go to vitamin K in the reduced form why is that important I'm glad you asked guys because guess what happens there's proteins factor to factor seven factor 9 factor 10 protein C and protein s so protein C and protein s and if you really want there's another one called protein Z but all of these guys this they're in this inactive form So in active when they interact with the vitamin K in the reduced form through a specific enzyme here called a carboxylase enzyme it converts these guys into their active form so that's important

here and again what is the enzyme that's triggering this process to go from the reduce back to the oxidized this is called a carboxylase enzyme okay so that is the significance there with the vitamin K now the vitamin A what's its significance here well the vitamin A Is pretty darn cool as well but there's not a lot that we really need to talk about with this one so for example here let's say I take the next one the vitamin A the vitamin A when we absorb it across our GI T and the font went within

the chylomicrons it's usually coming in the form of what's called retinol esters what happens is we take this bad boy to our liver okay and the liver let's draw another a baby liver okay what it does is it has Particular enzymes that convert the retinal esters into retinol and then another thing the liver does is it produces a protein that will actually bind on to the retinol look at this here we're gonna have a protein that binds onto we already mentioned this protein it's called retinal binding protein look at that and then guess what can

happen here this retinol when it's bound to the retinol binding protein we can take it to Different peripheral tissues what are some of the tissues one is it can go to the skin and the other one is we could take it to you know the rods ones then with inside of the eyes like particularly in the retina right because it's important for our dim vision so that's one thing another thing is we can take that retinol and instead of binding on to the retinal binding protein guess what we can do with that retinol we can

store it so it can be stored in these Special little cells located in the space of dissy and these are little cells here guess what these little buggers are these are called your stellate cells and your stellate cells are important because they can take that retinol and they can store it so that would be important within the storage of the actual vitamin a and then it can be released out into the circulation bind onto the retinol binding protein and then be utilized at different various Tissues right so that's the significance there the next one is

vitamin E now vitamin E is also important but he is really really specific in the antioxidant function so again we take it through the chylomicrons take it to the liver and the vitamin E okay it's actually carry view the chylomicrons when we take it to the liver what the liver actually does with it is it'll take the vitamin E and incorporate it into what's called your vldls So to incorporate it into the vldls and and also you know the vldls we know that some of it actually is converted into IDL some of those converting into

LDL s so what's important with this is it has the antioxidant function okay because you know what happens when the LDL particles can undergo oxidation it can lead to a theory Genesis so guess what this vitamin E is for its specifically carried within a lot of these lipoproteins to prevent the Oxidized particles from actually causing a lot of the theory a theory genic effects so with antioxidant function can be designed to try to decrease atherosclerosis or a thorough Genesis so that's pretty darn cool if you think about it okay now for the last two buggers

here let's say we have to talk about the last one here on the one more vitamin b12 again vitamin b12 not crazy a lot of stuff to talk about with this one just remember that vitamin b12 we Can actually take this and they can go it actually is transported to the liver so let's imagine here there's a transporting transport to the liver and when it's transported to the liver is actually transported by a specific protein produced by the liver so look at this there's a protein here made by the liver and this protein is called

trans cobalamin and if you want to be specific it's actually Transco Battlement type 2 and it binds onto the vitamin b12 and Takes it to liver and then the liver can actually store that vitamin b12 in the form of transcript element 1 or it can see crete that out right so we can take that vitamin b12 and we can take it to various tissues what's one tissue that is really needed for the vitamin b12 the bone marrow so we can take this to the red bone marrow right and the red bone marrow needs this and

the reason why the red bone marrow needs this is it's a precursor or a necessity for Erythropoiesis what else you know vitamin b12 is also really important for DNA synthesis it's involved in the folic acid pathway right so that's important too okay so we covered the basic of the vitamins now the next thing that I really want to talk about is the copper and the iron so let's say here I have we've already talked a lot about this and into in the individual videos but let's say here's an entire site and you know that the

iron is brought in to the Entire site via specific proteins like DMT one divalent metal transporter and then from here we can actually push it out through particular proteins located on the basolateral membrane this is the really important one called Ferro Porton if you guys remember it's very important or Ferro important and then what happens is the iron there is bound to a particular protein and what is that protein here that binds on to it that protein is called transferrin and then That transferring if you guys remember is gonna take the iron to the liver

and the liver is gonna take up a lot of this so now that's gonna take up the iron and what its gonna do with the iron is it's gonna store it right so we can take this iron let's say here's the iron we can take it inside of this liver cells and we can bind it to what's called ferritin okay actually it's a originally a PO ferritin when it binds up to there and it becomes ferritin and if there's a lot Of ferritin molecules they can be converted into hemosiderin this is important because whenever there's

high levels of this hemosiderin or high levels of the iron the liver makes a protein called hepcidin and then hepcidin if you guys remember actually is responsible for regulating the ferroportin so if there is high levels of iron the actual liver will produce a protein called hap sidin Pepsodent won't hit but they're very important which Will inhibit the iron absorption why is this important because if some people are not able to release the hepcidin if there's a deficiency or mutation it can produce a disease refer to as chemo chroma ptosis okay why is this super

dangerous why is iron so dangerous if it's built up in a lot of levels high levels iron can actually react with hydrogen peroxide ins out of ourselves when it does that it converts the iron from the +2 state To the +3 state and it forms this really nasty molecule here called a hydroxyl radical and this guy can cause a lot of damage okay what kind of damage it can damage our proteins it can damage our D our DNA it can damage our cell membranes so super super nasty free radical and this can actually the dangerous

thing here is that sometimes this guy right here can go right back to the iron 2 plus by reacting with hydrogen peroxide this is really dangerous because this is Called your Fenton reactions and this is what's can be really dangerous because it can actually damage the liver cells and some of the iron can leak out into the blood and go to various tissues and damage those tissues as well okay and the last one that I want to talk about is copper so let's say we take the copper here let's do baby now let's actually do

this moraine all right so let's say here we have an entire site here and again we're gonna Take up our copper now here's what you got to remember there is these um little transporters there divalent metal transporters that take up the copper now the copper when we take this bad boy up we actually have the copper bound to another protein here let's say here's this protein this one transports it to the liver and this protein that binds onto it is actually called albumin and then what will happen is this copper will be transported to the

liver now What happens with this copper let's say we take this copper out here this copper here is super cool because what happens is he's gonna bind on - there's gonna be a kind of like a protein shuttle if you will let's go take this guy here let's draw him as a t piece be okay so he's a super important protein that binds on to the copper and takes the copper and puts them into two different destinations one is you can take the copper and transport it and Actually excrete it out into the bile okay

so it can be excreted into the bottle they're specific transporters like MDR one we'll talk about that multidrug-resistant transporters that it can excrete out the different types of organic cations okay another thing is and this is just a maintain we don't want to have copper build up inside of our liver cells because it's toxic it can actually cleave to free radical reactions some of it actually is going To bind onto the atp7b and it's going to be bound to it's gonna be transported and there's another protein inside of our cell called a PO Cerullo plasma

when it reacts here the atp7b transfers the copper onto the a place' Rula plasma and converts this bad boy into Cerullo plasma now here's the thing in a crazy disease called Wilson's disease there's damage or I should say damage there's a defect or mutation in which this atp7b isn't produced if that's the case the Copper can't be excreted into the bile and the copper can't be bound on to a ceruloplasmin so the free copper starts rising inside of the actual liver cells why is this bad same thing is that copper what it can do is

it can react with hydrogen peroxide and when it reacts with the hydrogen peroxide guess what it does it takes and convert that into copper 2 plus and this super dangerous molecule let's put him in pink here the hydroxyl radical and again what Can this guy do he can lead to a lot of oxidative stress he can damage your DNA he can damage your proteins he can damage the cell membrane via lipid peroxidation and so it's a really really nasty little thing here so again this is really important that we should understand how the liver is

actually storing all of these different types of fat soluble vitamins are water soluble vitamin storing iron and storing copper because if for just some reason There's a mutation in this gene it can produce Wilson's disease and Wilson's disease you actually know you can see that one of the diagnostic signs copper can actually get put into a specific membrane inside of the corner there's what's called the Desmond's membrane and when the copper accumulates there produces these like brown pigmented rings called Kaiser Fleischer rings and that can be one of the diagnostic signs that there could be

a copper Accumulation and also can start really damaging your central nervous system if you guys watch this whole video can't thank you guys enough I really appreciate it if you guys like this video please I'm begging you hit that like button comment down in the comment section and please subscribe also if you guys get a chance to go check out our Facebook or Instagram and even our patreon account alright and engineers as always until Next time [Music] you