Bile acids and bile salts

one of the major purposes of cholesterol is to help synthesize something called bile so bile is an aqueous mixture that is produced inside the liver and helps emulsify and break down fat that we ingest into our body so let's begin by talking about the composition of bile so bile contains inorganic compounds and organic compounds so here we have bile our aqueous mixture produced inside the liver and so we have inorganic compounds that just simply means we don't have any carbon and then we have organic compounds which means we do have carbon so the inorganic compound is water in fact about 95 percent of bile is actually water and so that's why we call this an aqueous mixture and then we have a variety of organic compounds and this makes up a total of about five percent now depending on the sources you use sometimes these percentages can be little different but for the most part we have 95 percent water and five percent organic compounds now for the organic compounds the major organic compounds are bile salts and as we'll see bile salts are simply conjugated versions of bile acids and they make up about 51% of the total composition of the organic compounds and then we have phospholipids the major phospholipid is lesson lesson is also known as phosphatidylcholine and this makes up about 25 percent of the composition of the organic components and then we have a bunch of other things for example we have bilirubin we have fatty acids we have cholesterol itself in the unmodified form and so forth so because by far the major organic molecule are is the bile salt this is what we're gonna focus on in this lecture so remember when we ingest food that is rich in fat the liver can synthesize and release bile directly into the duodenum the bile is important in breaking up the fat and emulsifying the fat and that prepares it for absorption by the intera sides the cells of our small intestines now in between meals we can actually store bile in an organ known as the gold bladder the gold bladders found right below the liver so let's begin by talking about bile acid so bile acids are these organic molecules that contain twenty four carbon atoms so here we have one example of a bile acid known as Kolak acid so we have one two three four of these rings that consists of carbon and we also have this hydrocarbon chain on one end and together if we count we have twenty four carbon atoms then depending on the bile acid we can either have two or three hydroxyl groups so for Kolak acid we have one two three hydroxyl groups we also have some methyl groups so we have one two methyl groups and then we have the hydrocarbon chain and on the end that we have a carboxyl group now the carboxyl group has a pKa of about 6.0 which is below and relatively close the normal physiological pH of about seven point two and so what that means is this bile acid will remain in the partially dissociated form so some of the colic acid will contain a negative charge while some will still contain that H+ atom now bile acids are what we call amphipathic molecules so they they contain hydrophilic regions and hydrophobic regions so these hydroxyl groups actually have alpha orientation so they lie above the plane of the molecule and that means above the plane we're gonna have hydrophilic regions these regions are going to be able to interact with the aqueous environments below the plane we have these methyl groups so the methyl groups have beta orientation they lie below the plane and so below the plane we're gonna have hydrophobic regions this regions can interact with the fats that we ingest into our body and that's why these molecules are great emulsifying ages the methyl groups which are hydrophobic can interact with the fat breaking up the fat while the hydroxyl groups can interact with the nearby aqueous environment now how do we synthesize these bile acids so bile acids are synthesized from cholesterol so we have this multi-step multi organelle process in which cholesterol is ultimately converted into primary bile acids so the two major primary bile acids you have to be familiar with is Kolak acid which we talked about here as well as Kino deoxycholic acid now in this process essentially we reduce the number of carbons by 3 so cholesterol has 27 carbon atoms while these primary bile acids only have 24 carbon atoms and so that means we remove 3 carbon atoms from this hydrocarbon chain in addition we add the carboxyl group at the end of the hydrocarbon chain we also reduce these rings and then we can add hydroxyl groups as well now we're not going to talk about the details of this process but I will talk about the rate limiting step of this process the rate limiting step of forming bile acids from cholesterol is catalyzed by an enzyme known as cholesterol 7 alpha hydroxylase so this enzyme is only found in hepatocyte in the liver cells and it's bound to the ER membrane so it's basically a cytochrome p450 enzyme and so this enzyme is up regulated by high levels of cholesterol so if we have high levels of cholesterol inside the liver cells it will up regulate the activity of cholesterol 7 alpha hydroxylase allowing us to form more primary bile acids but as we increase the amount of primary bile acids for example as the Kolok acid levels increase this creates a negative feedback loop that decreases the expression and activity of cholesterol 7 alpha hydroxylase so higher levels of cholesterol stimulate this enzyme while high levels of the products the cola Cassatt down regulates the activity of cholesterol 7 alpha hydroxy Lang's now once we form the bile acids this is not the end of the story once we form the bile acids before the liver cells can release the bile acids their first conjugated with either glycine or Turin to form bile salts so if we take the bile acid and we conjugated we form a bile salt and bile salts are actually better emulsifying agents than bra than bile acids why well if we add a glycine or taurine to the end of this carboxyl carboxyl group we actually lower the pKa value of this group and by lowering the pKa value that means these molecules will exist predominantly in a fully ionized form and the fully ionized form is better able to dissolve in the aqueous solution than the on ionized form that doesn't contain any charge and so in general bile salts are better able to dissolve in the aqueous environment than the bile acids and so bile salts are much better at emulsifying fats than bile acids in fact bile acids when they travel inside the blood they actually need a transport molecule such as albumin in contrast bile salts can simply travel within the blood without without being balanced at any type of transport molecule so let's summarize what we talked about so far via this multi-step multi-organ lproj Multi organelle process inside the liver cells cholesterol can be transformed either to Kolak acid or Kino deoxycholic acid the two types of bile acids then in the liver we can conjugate Kolak acid with either taurine in which case we form torque oleic acid or glycine in which case we form glycolic acid if we take Kino deoxycholic acid and we add taurine we form Toro Kino deoxycholic acid if we add glycine we formed like kino deoxycholic acid and these bile salts are better able to dissolve in the aqueous environment and so they're better emulsifying agents compared to bile bile acids now in addition to aiding in in addition to aiding in fat digestion via emulsification these bile salts are also important because we can actually excrete cholesterol from the body via this process so bile salts also provide the only major method of cholesterol excretion as we'll talk about in just a moment so I want to briefly mention that the ratio of glycine to taurine forms is actually three to one so we have more of the glycolic acid and glyco Kino deoxycholic acid compared to Tora Kolak and taro Kino deoxycholic so let's finish off by talking about the entero hepatic circulation so in the liver cells we generate the primary bile acids those are then conjugated to form the bile salts and the bile salts are either stored in a gold bladder or released into the duodenum so if we ingest food that is rich in fat the bile mixes with the fat in the duodenum and begins to break it down now as the bile salts move along the duodenum and the remainder portion of the intestines the bacteria can actually modify the bile salts so the bacteria can convert the bile salts back to the primary bile acids by removing touring or glycine and the bacteria can also then convert the primary bile acids to secondary bile acids by removing hydroxyl groups and so now in the ileum we have a mixture of bile salts primary bile acids and secondary bile acids and about 95 percent of this solution is actually actively reabsorbed back into the portal circulation from the ileum so the bile salts and acids basically movie the pea via the portal veins back into the liver and now the liver can read the majority of these molecules in the same exact process and this is what we call in taro hepatic circulation and Terra means the intestines and hepatic means the liver now notice about five percent of the bile salts and assets can actually be excreted in the feces and so that's why this provides the only major method of cholesterol excretion so by converting cholesterol into the primary bile acids and then conjugating them into the bile salts some of them can actually be excreted in the feces and so in this way we can rid the body of cholesterol if we have too much cholesterol within our blood and so we can actually use this and develop drugs to help excrete more cholesterol out of the intestine so we have medications known as a colas thyromine so colas thyromine is an oral medication that we ingests orally and it moves into the duodenum where it binds and sequester's bile acids and prevents their reabsorption by very absorption in an ileum and so ultimately were able to excrete more of that cholesterol in the feces and that can decrease cholesterol levels in the body dietary fiber can do exactly the same thing dietary fiber can also bind and sequester these bile acids and this can decrease the amount of cholesterol inside our body so patients who have high levels of cholesterol can take dietary fiber or these medications to help decrease the amount of cholesterol within our body and within our bloodstream

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Keywords: bile, bile acids, bile salts, synthesis of bile, synthesis of bile acids, synthesis of bile salts, enterohepatic circulation

Id: wAa6a1AKdog

Length: 12min 49sec (769 seconds)

Published: Sat Jun 29 2019