What is bile?
Bile consists of a watery mixture of organic and
inorganic compounds.
Bile is synthesized in the liver and it gets
pumped out through common bile duct to the
duodensem (small intestines) then it get
reabsorbed
Some is stored in the gallblader
Phosphatidylcholine (PC) and conjugated bile salts are the most important organic components
of bile.
Structure and protonation states of bile acids
The bile acid (are modified from cholesterol) it is an amphipathic
molecule that contains 24 carbons, with two or three hydroxyl
groups and a side chain that terminates in a carboxyl group
The carboxyl group has a pKa of ~6.
In the duodenum (pH ~6), this group will be protonated in half
of the molecules (the bile acids) and deprotonated in the rest
(the bile salts).
Synthesis of primary bile acids
One of the main differences between cholesterol and bile acids
is the presence of hydroxyl groups, so there is an enzyme
(cholesterol 7-alpha-hydroxylase) that inserts hydroxyl groups
into cholesterol.
This reactios is the commited step (rate limiting step)
Expression of the enzyme is downregulated by bile acids.
The 7-α-hydroxylase is a SER-associated cytochrome P450
monooxygenase found only in liver.
Then it will be modified by many things such as 1.The
double bond of the cholesterol B ring is reduced 2.The
hydrocarbon chain is shortened by three carbons 3.
Introducing a carboxyl group at the end of the chain.
Producing one of the 2 forms of bile acids
Bile consists of a watery mixture of organic and
inorganic compounds.
Bile is synthesized in the liver and it gets
pumped out through common bile duct to the
duodensem (small intestines) then it get
reabsorbed
Some is stored in the gallblader
Phosphatidylcholine (PC) and conjugated bile salts are the most important organic components
of bile.
Structure and protonation states of bile acids
The bile acid (are modified from cholesterol) it is an amphipathic
molecule that contains 24 carbons, with two or three hydroxyl
groups and a side chain that terminates in a carboxyl group
The carboxyl group has a pKa of ~6.
In the duodenum (pH ~6), this group will be protonated in half
of the molecules (the bile acids) and deprotonated in the rest
(the bile salts).
Synthesis of primary bile acids
One of the main differences between cholesterol and bile acids
is the presence of hydroxyl groups, so there is an enzyme
(cholesterol 7-alpha-hydroxylase) that inserts hydroxyl groups
into cholesterol.
This reactios is the commited step (rate limiting step)
Expression of the enzyme is downregulated by bile acids.
The 7-α-hydroxylase is a SER-associated cytochrome P450
monooxygenase found only in liver.
Then it will be modified by many things such as 1.The
double bond of the cholesterol B ring is reduced 2.The
hydrocarbon chain is shortened by three carbons 3.
Introducing a carboxyl group at the end of the chain.
Producing one of the 2 forms of bile acids
