288
CASE FILES: BIOCHEMISTRY
Figure 31-3. The enterohepatic circulation of bile acids.
deleterious events involving the metabolic pathways of cholesterol or the bile
acids/salts. First, the cholesterol concentration in bile becomes supersaturated.
Bile is a controlled mixture of cholesterol, bile acids, and phospholipids (with
small amounts of bile pigments), and if cholesterol levels are elevated or bile
acids/salts lowered, the ratio of the three major components changes leaving
cholesterol less protected against the aqueous environment and more likely to
precipitate. Elevated cholesterol levels can occur by having excess HMG-CoA
reductase activity, the rate-limiting enzyme in cholesterol biosynthesis; this
condition is typically seen in the obese. Alternatively, reduced levels of acyl-
CoA: cholesterol acyltransferase [ACAT], the enzyme that esterifies choles-
terol within cells, or reduced levels of cholesterol 7a-hydroxylase can cause
elevation of cholesterol. Deoxycholate, a secondary bile acid synthesized by
intestinal bacteria, inhibits
CYP7A1.
Therefore, high levels of deoxycholate
previous page 302 Case Files   Biochemistry read online next page 304 Case Files   Biochemistry read online Home Toggle text on/off