Bile Salt Formation

[liveonearth]

What the first step in making bile?
7 alpha hydroxylation of cholesterol
this is the rate limiting step, inhibited by presence of bile acids
cyp enzyme requires iron 2+ and NADPH, and forms water

What happen to iron in the reaction?
Fe2+-->3+


What steps follow the initial hydroxylation?
reduction of the 4,5 double bond, oxidation of the side chain

7 alpha-hydroxycholesterol is converted eventually to what two acids?
chenocholic and cholic acid
chenocolic has hydroxyls at positions 3 and 7
cholic has them at 3, 7, 12

What hormone stimulates bile release?
CCK

What are the conjugates used?
glycine or taurine
bile acids not conjugated
bile salts are conjugated

What's the pK of bile salts?
pH ~6

How much of bile salts are recycled?
95%
5% are excreted because intestinal bact deconjugate, dehydroxylate
this makes them less soluble

GILBERT'S SYNDROME
AKA Gilbert-Meulengrachts syndrome
most common hereditary cause of increased bilirubin
in 5-10% of pop
harmless jaundice
dt reduced activity of the enzyme glucuronyltransferase
which conjugates bilirubin and some other lipophilic molecules
conjugation renders the bilirubin water-soluble, after which it is excreted in bile into the duodenum