CASE FILES: BIOCHEMISTRY
A nsw ers
D. Although a cholesterol-rich gallstone cannot be completely ruled
out with the given information, because the patient has experienced
several mild sickle cell crises that are accompanied by increased red
blood cell destruction, his symptoms are consistent with a gallstone
caused by precipitation of calcium salt of bilirubin. Large quantities
of bilirubin can overwhelm the ability of the liver to convert it to the
more soluble diglucuronide conjugate. As a consequence, the more
insoluble unconjugated form enters the bile and is easily precipitated
in the presence of calcium ion. If a large stone forms, it can obstruct
the bile duct and result in the symptoms exhibited by the patient.
D. Cholestyramine binds bile acids strongly so that they cannot be
reabsorbed in the intestinal tract, thus increasing the flow of choles-
terol to bile acid synthesis and decreasing cholesterol levels in the
plasma. However, by binding bile acids, cholestyramine also
decreases the absorption of fat-soluble vitamins and fatty acids,
which must be taken up in micelles formed with bile acids. Although
absorption of vitamin A and linolenic acid may be compromised, the
patient needs to be concerned about vitamin K, which is required for
blood clot formation.
A. The enzyme sterol 27-hydroxylase catalyzes the hydroxylation of
carbon 27 of the steroid side chain in the conversion of cholesterol to
the primary bile acids. It is a mitochondrial, cytochrome P450 enzyme
that has a broad specificity and can act on cholesterol as well as its
reduced and hydroxylated metabolites. A deficiency in this enzyme
leads to decreased bile acid synthesis and increased conversion of cho-
lesterol to cholestanol.
B IO C H E M IS T R Y PE A R L S
There are two primary bile acids formed in the liver from choles-
terol: cholic acid and chenodeoxycholic acid.
Ursodeoxycholic acid has been reported to have good efficacy in
treating the symptoms of pregnancy-related cholestasis, relieving
both pruritus and liver function abnormalities.
Cholestyramine can interfere with the absorption of fat-soluble vita-
mins, such as vitamins A, D, E, and K.