426
chapter 19
Lipids II: Phospholipids, Glycosphingolipids, and Cholesterol
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LIVER
C holesterol
| Rate-limiting step
7 a -Hydroxycholesterol
Cholyl-CoA + C henodeoxycholyl-C oA
(Synthesis: 0 .5 g/d)
T a u rin e-^
C o A S H ^
Taurocholic acid
+ Tauro-CDCA
-Glycine
^-CoASH
G iycocholic acid
+ G lyco-CDCA
=
т И
=
Temporary storage of conjugated bile acids
GALLBLADDER
/
\
______________
-----------7^-----
Tauro- and giyco-
cholic acid
Tauro- and glyco-
CDCA
D eoxych olic,
..................
Lithocholic
acid
-(S econ d ary bile acids)*
acid
INTESTINE
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ta
cr
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Q .
F ecal excretion
(-5 -1 0 % , or
-0 .5 g/d, m ostly secon dary bile acids)
F IG U R E 1 9-20
Form ation, enterohepatic circulation, and disposition o f the bile acids. CD CA = Chenodeoxycholic acid.
of each meal. The amount of bile acids lost in feces is
about
0
.
8 - 1
g/day and consists mostly of secondary bile
acids (particularly lithocholic acid, the least soluble of the
bile acids). The loss is made up by synthesis of an equal
amount in the liver.
Bile Acid Metabolism and Clinical Medicine
In liver disorders, serum levels of bile acids are elevated,
and their measurement is a sensitive indicator of liver dis-
ease. Bile acids are not normally found in urine owing
to efficient uptake by the liver and excretion into the in-
testines. In hepatocellular disease and obstructive jaun-
dice, however, their urinary excretion increases.
Lithocholic acid is toxic and can cause hemolysis and
fever. Effects associated with hyperbile acidemia include
pruritus, steatorrhea, hemolytic anemia, and further liver
injury.
The main cause of
cholelithiasis
(presence or forma-
tion of gallstones) is precipitation of cholesterol in bile.
Elevated biliary concentrations of bile pigments (bilirubin
glucuronides) can also lead to formation of concretions
known as pigment stones (Chapter 29). Since biliary
cholesterol is solubilized by bile acids and lecithin, an
excess of cholesterol along with decreased amounts of
bile acids and lecithin, cause bile to become supersatu-
rated with cholesterol with the risk of forming cholesterol
stones. The limits of solubility of cholesterol in the pres-
ence of bile salts and lecithin has been established by using
a ternary phase diagram. If the mole ratio of bile salts and
phospholipids to cholesterol is less than
1 0
:
1
, the bile is
considered to be lithogenic (stone forming), but this ra-
tio is not absolute. The pattern of food intake in Western
nations, which consists of excess fat, cholesterol, and an
interval of 12-14 hours between the evening meal and
breakfast, leads to a fasting gallbladder bile that is sat-
urated or supersaturated with cholesterol. In individuals
who have gallstones, the problems associated with pro-
duction of lithogenic bile appear to reside in the liver and
not in the gallbladder. When the activities of HMG-CoA
reductase and 7a-hydroxylase were measured in the liver
of patients who had gallstones and compared with those
