Bile Acids

[aspiringmd1015]

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Bile acids are conjugated to glycine and taurine to make them more water soluble. WHats the purpose of making them more water soluble? and does this assist at all in micelle formation in the gut? and what is their function in making cholesterol more soluble in bile? highly confused, thanks

 

[StilgarMD]

Bile acids are cholesterol molecules with amino acids bound to them to make them water soluble. They are loaded into Bile, stored, and released when fat is in the duodenum. There, the amphipathic nature of the molecule (the cholesterol end is hydrophobic, the AA is hydrophilic) allows it to emulsify fat, which is just a way to increased the surface area dramatically. This surface area gives more contact with the contents of Pancreatic secretions (specifically lipases here), which allows them to chew up the fat into TAGs into Glycerol and Fatty acids. These two, along with cholesterol, can passively diffuse into the epithelia of the jejunum and are packaged into Micelles, which are taken up by Lacteals (lymph vessels) and eventually reach the blood.

Bile acids aren't conjugated to glycine and taurine. 7-alpha-Cholesterol is conjungated to glycine and taurine to make Bile acids. If they aren't sufficiently water soluble, they wouldn't be that useful as emulsifying agents inside the gut - they'd just make the fat globs bigger by being absorbed into them, instead of breaking them up. When it comes to making cholesterol more soluble in bile, I think about it as follows

10 units of Cholesterol floating in Bile = Very likely to precipitate (they're hydrophobic and will try to shield each other from water)
3 units of Cholesterol + 7 units of Cholesterol bound to Amino acids (I.e. bile acids) = Much less likely to precipitate.

If you use a drug, like a fibrate, that inhibits the production of Cholesterol 7-alpha hydroxylase, which manages the rate limiting step of cholesterol's conversion into a bile acid, then you make less bile acids and end up with more free cholesterol in the bile. This increases your chance of ending up with a bile gallstone. a similar risk exists when you use Bile acid sequesterants because than the Liver needs to make more cholesterol and bile acids from scratch and puts more cholesterol in the Bile.

Just for reference - none of this stuff is particularly soluble - From Wiki: The composition of gallbladder bile is 97% water, 0.7%[1]bile salts, 0.2% bilirubin, 0.51% fats (cholesterol, fatty acids and lecithin),[1] and 200 meq/l inorganic salts.[2]. You can see how a small change in cholesterol can lead to a much greater chance of stones.

 

[aspiringmd1015]

UW directly tol dme that bile acids are conj to glycine and taurine. Thanks for the help though really appreciate it. and :

Pigment stones (black = radiopaque, Ca2+ bilirubinate, hemolysis; brown = radiolucent, infection)—seen in patients with Crohn disease, chronic hemolysis, alcoholic cirrhosis, advanced age, biliary infections, total parenteral nutrition (TPN).

Thats what first aid says, why is TPN and alcoholic cirrhosis specific for pigment stones

 

[EmCEm]

Bile acids are conjugated to glycine and taurine to make bile salts which are the more water soluble form (lower pka) from my understanding

 

[StilgarMD]

Bile acids are conjugated to glycine and taurine to make bile salts which are the more water soluble form (lower pka) from my understanding

I was going off this picture: https://upload.wikimedia.org/wikipedia/commons/c/c4/Bile_acid_differentiation.svg

Initially I didn't believe what you'd just written, since my understanding is a Salt is two charged species held together by differences in charges, but Wiki confirms the convention:
"These conjugated bile acids are often referred to as bile salts because of their physiologically-important acid-base properties. The pKa of the unconjugated bile acids are between 5 and 6.5,[7] and the pH of the duodenum ranges between 3 and 5, so when unconjugated bile acids are in the duodenum, they are almost always protonated (HA form), which makes them relatively insoluble in water. Conjugating bile acids with amino acids lowers the pKa of the bile-acid/amino-acid conjugate to between 1 and 4. Thus conjugated bile acids are almost always in their deprotonated (A-) form in the duodenum, which makes them much more water-soluble and much more able to fulfil their physiologic function of emulsifying fats.[8][9]"

 

[walakin25]

just to add to poster above, by lowering the pka, it keeps the bile acids in a deprotonated state and hence water soluble which is as key for optimizing emulsification properties which @StilgarMD pretty much explained perfectly. in alcoholic cirrhosis, there is hemolysis from various reasons: 1) bleeding varices 2) ineffective erythropoesis, folate deficiency and macrocytic anemia. not 100% sure about TPN but might have something to do with increased risk of infections

edit: a little late to the game oops

 

[aspiringmd1015]

okay excellent, so making them water soluble aids in their emuslifying ability, does it also help in their ability to solubilize cholesterol and bilirubin in the bile?
theres hemolysis in varices? ineffective erythropoeisis in alcoholism makes sense, no folate, so cells will be prematurely destroyed within the RES/BM

 

[walakin25]

my bad about the varices, i was thinking about something else and misplaced it here. anyways other mechanisms of increased hemolysis are 1) hypersplenism --> RBCs sequestration, increased destruction) and 2) altered RBC membrane composition yielding acanthocytes and stomatocytes. alteration in surface area to volume ratio decreases ability to squeeze through vessels and increases hemolysis. also increased peroxidation of membrane fatty acids and oxidative damage is implicated.

 

[aspiringmd1015]

by what stiglarMD said, the way bile salts make cholesterol more soluble, is by reducing the total amount of cholesterol by converting them into bile acids?

 

[walakin25]

yes