C— N-CH,-C —O
glycine conjugate
c — N -C hL-C H z-S-O
taurine conjugate
Figure 31-2. Conjugation of bile salts.
secreted through the bile ducts, which are made up of the bile canaliculi and
bile ductules, and passed on to the gallbladder for storage as bile. Ultimately,
they are passed on to the intestine. Most of the bile acids/salts are deconju-
gated in the intestinal ileum and reduced to secondary bile acids by bacteria,
which remove the 7a-hydroxyl group by a dehydroxylation reaction. Although
some are lost by excretion, approximately 90 percent of the bile acids and salts
are reabsorbed in the terminal ileum and returned to the liver. The liver cannot
provide sufficient amounts of newly synthesized bile acids for the body’s daily
needs; therefore, the body relies on enterohepatic circulation (Figure 31-3) to
sustain necessary bile acid levels. The portal vein transports bile acids from the
intestine back to the liver as complexes with serum albumin.
The synthesis of bile salts is under very tight regulatory control to maintain
cholesterol homeostasis and supply sufficient amounts of detergent to the
intestine. This is controlled in part by a feedback mechanism on cholesterol
7a-hydroxylase, the rate-limiting enzyme in the synthetic pathway. Increased
concentrations of bile acids inhibit cholesterol 7a-hydroxylase, while low lev-
els relieve the inhibition. Elevated cholesterol levels, however, activate the
enzyme, thus increasing bile acid biosynthesis. Levels of both cholesterol and
bile acids affect the concentration of cholesterol 7a-hydroxylase and this reg-
ulation appears to be controlled at the transcriptional level via nuclear recep-
tors. Therefore, binding of bile acids or cholesterol to a given nuclear receptor
in turn regulates the expression of the
gene, activating expression in
the case of binding to cholesterol and repressing it when bile acids are bound.
Thus, the proper maintenance of bile acid levels can prevent accumulation of
Eighty percent of gallstones in the Western world are a result of cholesterol
precipitation from the bile, a condition known as cholelithiasis. The patho-
genetic mechanism of gallstone formation usually involves a culmination of
previous page 301 Case Files   Biochemistry read online next page 303 Case Files   Biochemistry read online Home Toggle text on/off