D efinitions
Bile salts: Cholesterol derivatives with detergent-like properties used to
solubilize cholesterol, assist in intestinal absorption of fat-soluble vita-
mins, and emulsify dietary lipids passing through the intestine to enable
fat digestion and absorption by exposing fats to pancreatic lipases.
Bile acids: Neutral, protonated form of bile salts.
Primary bile acids: Synthesized from cholesterol as cholic acid and chen-
odeoxycholic acid. They are secreted as taurine and glycine conjugates.
Secondary bile acids: Products of deconjugated and reduced primary
acids. Bacteria in the intestine remove the 7a-hydroxyl group, leaving
the secondary bile acids.
Cholesterol 7a-hydroxylase
The mixed-function oxidase
cytochrome P450 enzyme catalyzing the initial, rate-limiting step for
conversion of cholesterol to bile acids.
b-hydroxy-b-methylglutaryl-coenzyme A (HMG-CoA) reductase: The
rate-limiting enzyme in cholesterol biosynthesis.
Bile salts are derivatives of cholesterol that make up the major component of
bile. They are very efficient detergents when conjugated to amino acids
because of the presence of both polar and nonpolar regions. This property
helps to emulsify dietary lipids in the intestine, which aids in fat digestion and
absorption by making fat vulnerable to pancreatic lipases. Other functions of
bile salt (ionized, deprotonated form) and bile acid (neutral, protonated form)
are to solubilize cholesterol thus preventing precipitation of cholesterol crys-
tals and facilitating cholesterol excretion. The only significant removal of
excess cholesterol from the body is achieved through the excretion of bile
salts. Finally, they assist in intestinal absorption of fat-soluble vitamins.
The conversion of cholesterol to bile acids is a multienzyme process. The
initial and rate-limiting step of bile acid synthesis is oxidation of choles-
terol to 7a-hydroxycholesterol by a mixed function oxidase from the
cytochrome P450 superfamily, cholesterol 7a-hydroxylase
Figure 31-1). The remaining steps include reduction of the A5-double bond,
side chain shortening, and oxidation. The products of this pathway, cholic acid
and chenodeoxycholic acid, are termed the primary bile acids because they
have been synthesized de novo from cholesterol. To increase the pH range over
which the bile salts remain ionized and serve as good detergents, they may be
conjugated via amide bonds with either of the amino acids glycine or taurine
(Figure 31-2).
Bile salts/acids are synthesized in the liver, stored and concentrated in
the gallbladder, and secreted into the intestine where they may undergo
deconjugation and reduction by intestinal bacteria to produce secondary bile
acids (see Figure 31-1). Once formed in the liver, the bile salts/acids are
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