Bile Acids and Salts

Question 1

3 fates of hepatic cholesterol

Answer 1

1. incorporated into hepatic membranes
2. exported in VLDLs
3. secreted into biles as free cholesterol and bile salts

Question 2

monooxygenases

Answer 2

mixed function oxidases

catalyze the oxygenation of cholesterol into its derivatives

use O2 to oxidize 2 different substrates

cytochrome p450 family

Question 3

cholic acid

Answer 3

primary bile acid - major one

Question 4

what separates primary from secondary bile acids

Answer 4

C-7 hydroxylation on the primary acid

Question 5

monooxygenase 7alpha-hydroxylase (CYP7A1)

Answer 5

starts cholesterol –> bile acid

adds OH to C7 position

rate limiting reaction

Question 6

regulation of 7alpha-hydroxylase (CYP7A1)

Answer 6

transcriptionally regulated

short half life

transcription is feedback inhibited

Question 7

bile salts

Answer 7

bile acids that are conjugated with either taurine or glycine

bile salts are secreted into the intestine, not bile acids

lower pKa than bile acids…so in intestine (ph ~6)

bile salts are all in ionic form…and bile acids are 50% ionized….

makes bile salts better detergents

Question 8

the more OH groups…the more polar….therefore

Answer 8

more readily reabsorbed and enter enterohepatic circulation

best = cholate = 3 OH groups

Question 9

bile salt deficiency (cholelithiasis)

Answer 9

if more cholesterol enters bile than can be solubilized by the bile…cholesterol will make gallstones