Bile Metabolism Flashcards
(34 cards)
List the 3 major components of solids dissolved in bile.
Bile is an aqueous solution of bile acids/salts, phospholipids (lecithin) and cholesterol. These compounds comprise 80% of the total solids dissolved in bile.
Define the 2 major functions of bile.
- Emulsify fats and fat soluble vitamins (ADEK), aids in lipid digestion and absorption via amphipathic bile salts
- Provide a means of excretion for cholesterol and bilirubin (breakdown of Hb)
What happens to bile when someone fasts? What happens after a meal?
When fasting, bile is stored in the gallbladder where most of the body’s bile salt pool is found. Post-prandially, CCK promotes the release of bile into the duodenum and the Sphincter of Oddi to relax.
Describe the 2 primary bile acids that are derived from cholesterol.
Both of these bile acids have 24 carbons as opposed to 27 in cholesterol and gained a carboxylate group.
- Cholic acid - has the 12-hydroxyl that Chenocholic acid lacks.
- Chenocholic acid
Bile acids are ______ planar molecules, meaning they are _____ on one side compared to the other.
Amphipathic planar molecules are HYDROPHILIC on one side compared to the other.
What enzyme is responsible for catalyzing the RDS in biosynthesis of bile acids from cholesterol? What are it’s allosteric effectors?
7-alpha hydroxylase (CYP7A1) adds a hydroxyl group to C7 @ cholesterol in the RDS for BA biosynthesis. This produces 7-alpha-hydroxycholesterol. Cholesterol stimulates the enzyme whereas cholic acid (product) is the negative allosteric effector.
The conjugation of bile acids in the liver with ____ or ____ lowers their pKa. What bile acids do each form, respectively?
Addition of taurine to cholic acid forms taurocholic acid (pka = 2). The addition of glycine makes glycocholic acid (pka = 4)
If the pH of the duodenum is 6, what is the status of cholic acid (pKa = 6) in the duodenum?
Neutral (half protonated and half deprotonated)
In the duodenum, the primary bile acids are more _____ because their pKa’s are ___ than the pH in the duodenum.
Primary bile salts are more HYDROPHILIC because their pKa’s are LOWER than duodenum’s pH. This makes them better at emulsifying fats.
Which are the least soluble in water and most hydrophilic, respectively in the list (cholesterol, cholic acid, chenodeoycholic acid, glycocholic acid)?
Most hydrophobic = Cholesterol;
Most hydrophilic = Glycocholic acid (lowest pKa = more ionizable in water)
Describe the process of emulsification by bile acids/salts.
Bile salts with their hydrophobic face stick to clumpy fat globules and pull them apart into smaller pieces that are more digestible for lipases. The forming micelles help with fat absorption.
What happens to bile acids in the lumen by the time they reach the terminal ileum?
Up to 95% of the bile acids is reabsorbed from the lumen back into circulation (portal vein) by the time digested food reaches the distal intestines.
Since bile is toxic to bacteria in the gut, they all have what enzyme in common? What does this enzyme produce?
Gut bacteria all have the enzyme that is able to dehydroxylate primary bile salts by removal of the hydroxyl group at C7 and “deconjugate” them. This process produces secondary bile salts (deoxycholic acid and lithocholic acid)
Rank the following in terms of least soluble to most soluble. (Primary bile acids, cholesterol, secondary bile acids)
Cholesterol (hydrophobic) < Secondary bile acids (lost C7 hydroxyl group) < Primary bile acids
When the distal ileum is removed via surgery, there will be an increase in bile acid ____.
Bile salt synthesis by hepatocytes increases.
How are the negative effects of ileal resections managed?
By limiting dietary fat intake and supplementing the diet with medium-chain triglycerides and fat-soluble vitamins.
Excretion of _____ is the primary mechanism for eliminating cholesterol from the body.
Bile salts.
Describe how Bile Acid Sequestrant (i.e. cholestyramine = Questran) can treat a person with high cholesterol levels.
Sequestrants bind bile acids in the intestine. These BAS compounds prevent the reabsorption of bile acids and increase the conversion of cholesterol to bile acids, thus effectively reducing cholesterol levels.
What role does Soluble Fiber have on cholesterol levels?
Dietary fiber naturally sequesters bile acids to increase the elimination of cholesterol from the body.
Describe the 5 step mechanism to how bile is shuttled between hepatocytes and enterocytes (with transporters).
- From the portal vein, bile acid is cotransported into liver cell via NTCP.
- Bile is exported into the biliary canaliculi via BSEP
- From the apical membrane, bile is coupled to reabsorption with Na+ in distal ileum enterocyte.
- From the basolateral membrane, bile is effluxed into the portal vein via OST.
- BA is transported across the basolateral side of the hepatocyte from the hepatic sinusoidal capillaries.
A disparity in the balance of dissolved bile solids can result in ______.
Cholesterol-type gallstones from the formation of lithogenic bile, as from the supersaturation of cholesterol.
Maximal bacterial transformation of primary bile aids to secondary bile acids occurs in the _____.
Colon, where most of our gut bacteria lie.
The least soluble part of bile is ____. The components known for keeping this insoluble part in solution are ____ and ____.
Cholesterol is the least soluble part of bile. Phospholipids and bile salts keep it aqueous in bile solution.
The most common type of gallstones are from _____. The second most type of stones form from ____.
Cholelithiasis describes the condition of cholesterol gallstones. The second common form is from precipitation of bilirubin.
