Cholesterol And Bile Salt Metabolism

Question 1

Where are bile acids/salts Made?Stored?Release into?

Answer 1

Made in the liver, stored in the gallbladder, released into the small intestine.

Question 2

Where is the sphincter of Oddi located?

Answer 2

In between the gallbladder and small intestine

Question 3

Role of CCK

Answer 3

When you eat a Fatty meal, Fatty acids in The duodenum cause endocrine cells to release CCK. When CCK Is released it causes the relaxation of the sphincter of Oddi. Therefore, bile gets into the small intestine and forms micelles with the fat so that the fats can be digested by lipases. At the end of this process, the bile salts are returned back to the liver.

Question 4

What are some properties of bile salts that make them good detergents?

Answer 4

They are planar and amphipathic. They are made up of multiple rings and then many OH groups. So, you can hav the OH groups on the outer face and the rings be burning on the inside so that it can hold lipids.

Question 5

What are the two primary bile salts?

Secondary bile salts?

Answer 5

Primary - Colic acid, Chenodeoxycholic acid

Secondary - Deoxycolic acid, lithocolic acid

Question 6

CYP7A

Answer 6

The enzyme responsible for the committed step in the synthesis of bile from cholesterol. Cholesterol –> Cholic acid

Question 7

What is the feedback mechanism for the creation or lack of creation of bile salts?

Answer 7

Positive feedback - cholesterol

Negative feedback - colic acid

Question 8

What are the steps involved in synthesizing bile salts from cholesterol?

Answer 8

1) OH groups are added 2) Side chain is shortened 3) COO- group is added at the end of the side chain. 4) Double bond is reduced.

Question 9

What is the difference between colic acid and chenodeoxycolic acid?

Answer 9

The OH group at C12.

Question 10

What further modifications are done to the bile salts? WHy? Where?

Answer 10

Either taurine or glycine are added to COO- group at the end of the carbon side chain. This further increases the hydrophilicity of the molecule. This occurs in the liver.

Question 11

What further modification occurs to these bile salts in the gut?

Answer 11

In the gut, gut bacteria remove the glycine and taurine residues from the bile salts. The gut bacteria can then dehydroxylate the bile salts to form Deoxycolic acid or lithocolic acid.

Question 12

what is conjugated bile salt? Unconjugated bile salt?

Answer 12

Conjugated would be when the taurine and glycine are attached. Unconjugated is after these groups get taken off.

Question 13

What would you expect the compositions of bile salts to the in the Liver? Feces?

Answer 13

Liver - Mostly colic acid and chenodeoxycolic acid with a little bit of lithicolic and Deoxycolic acid.
Feces - entirely lithicolic acid and deoxycolic acid

Question 14

What happens once the conjugated bile salts are formed?

Answer 14

95% are reabsorbed in the terminal ileum via the hepatic portal vein. The other 5% or so goes to the colon where they are deconjugated and dehydroxylated and eventually excreted in the feces.

Question 15

If the terminal ileum were to be removed, what would you expect to happen?

Answer 15

You would have loss of reabsorption of bile acids and therefore there will be no feedback inhibition from the colic acid because it will reach the colon and then get excreted. Therefore, there will be an increase in the creation of bile salts.

Question 16

Bile Acid Sequestrants

Answer 16

BAS can bind to the Bile salts and take them out of circulation. If bile acid concentration in the blood gets too low then cholesterol will be up taken into the liver to make more bile salts. Therefore it can lower cholesterol levels.

Question 17

What are the major transporters involved in the transport of bile acids throughout the process?

Answer 17

1) NTCP - Will bring sodium and bile acids into the hepatocytes from the Sinusoidal space.
2) BSEP - will bring Bile Salts from hepatocytes to caniliculus
3) ASBT - will bring Sodium and Bile Salt from the lumen into the ileal epithelial cells.
- remember not all bile salts will be up taken into the ileal epithelial cells. Some will continue on into the colon and be excreted into the feces.
OSTalphaBeta - The Bile salts will then make its way into the portal vein in order to be recycled.

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Question 18

What is responsible for Dehydroxylating bile acids?

Answer 18

Bacterial enzymes in the intestine.

Question 19

Cholelithiasis

Answer 19

If more cholesterol comes into the bile than can be excreted, then the cholesterol may precipitate/crystallize in the gallbladder, leading to gallstone disease.

Question 20

What are some causes of Cholelithiasis?

Answer 20

• ileal disease
• bile duct obstruction
• hepatic dysfunction
• genetic susceptibility

Question 21

in each place that you can have a gallstone, what will be the associated symptoms?

Answer 21

Cystic bile duct - painful gallbladder contractions
Common bile duct - no bile release into the duodenum, grey feces, can’t digest fatty meal, diarrhea, fatty feces, jaundice.
Duodenal papilla - no release of bile or pancreatic enzymes into t he duodenum so you can get pancreatitis, malnutrition.

Question 22

Morphological characteristics of cholestasis?

Answer 22

Hepatocytes are enlarged, apoptosis, kupffer cells with bile pigments, dilated canilicular spaces.

Question 23

what is the makeup of bile?

Answer 23

Bile acids, phospholipid, cholesterol, protein and a little bit of bilirubin.

• If the proportions of these get out of whack then you will get gallstones.
• Bile acids should be in largest proportion and then phospholipid.

Question 24

What is responsible for converting the primary bile acids into secondary?

Answer 24

The intestinal bacteria will dehydroxylate the primary bile acids into secondary.

Question 25

What does it mean. For. Bile. Salt to be conjugated?

Answer 25

Add either a taurine or a glycine

Question 26

What is the order of bile salt creation starting at the liver?

Answer 26

1) Primary bile salts are made in the liver by hydroxylating cholesterol
2) These primary bile salts are then conjugated still in the liver
3) These conjugated bile salts are then unconjugated by gut/colon bacteria back into primary bile salts
4) The unconjugated primary bile salts are then dehydroxylated into secondary bile salts by the gut/colon bacteria

Question 27

How. Do we get rid of cholesterol?

Answer 27

The 5% that is not reabsorbed in the portal vein goes to the colon where it is unconjugated, dehydroxylated, and excreted from the gut.

Question 28

NTCP

Answer 28

Transports Na and Bile acids from the Sinusoidal space into the hepatocytes