Nutrition 445

Case Study 3
Due April 6, 2016
Hypercholesterolemia:
A 36-year old man was found to have hypercholesterolemia. A dietary evaluation indicated that
he was consuming about 600 mg/day of cholesterol. His plasma cholesterol concentration on
two separate occasions was approximately 330 mg/dL (8.5 mmol/L). Ultracentrifugal analysis
revealed that the cholesterol elevation was due to an increase in plasma LDL. He was treated
with a cholesterol-free vegetarian diet for 3 months, but his plasma cholesterol level decreased to
only 300 mg/dL (7.7 mmol/L). Subsequently he was treated with colestipol hydrochloride, a bile
acid-binding resin that is not absorbed. This treatment lowered the fasting plasma cholesterol
concentration to 250 mg/dL (6.4 mmol/L).
Questions:
1. How is dietary cholesterol absorbed?
In humans, cholesterol absorption occurs mostly in the duodenum and proximal jejunum
of the small intestines, where both dietary cholesterol and biliary cholesterol are available
for uptake from the intestinal lumen (Lang, 2004).
Only about half of intestinal cholesterol is absorbed and the other half is excreted as
feces. A large portion of cholesterol from the diet is considered an ester, so it must be
hydrolyzed to free cholesterol in order to be absorbed (Gropper, Smith and Groff, 2009)
There are two main phases of cholesterol absorption. The first phase takes place in the
lumen. Within the lumen, digestion and hydrolysis of lipids occur, followed by
solubilization of cholesterol in mixed micelles containing bile acid and phospholipids.
The second phase is where cholesterol crosses the mucosal cell membrane by simple and
facilitated diffusion. Once in the cell, the cholesterol is re-esterified and incorporated into
Apo-B-containing nascent lipoproteins that are secreted into the lymph (Turley &
Dietschy, 2003).
Cholesterol must pass through the unstirred water layer acting as a diffusion barrier at the
lumen-enterocyte membrane interphase, since cholesterol is found in the intestinal
micelle. Free cholesterol is an energy-independent process. It is also facilitated by
specific transporter proteins, like the transmembrane protein, NPC1L1.
Once cholesterol is absorbed in the enterocyte, it is transported to the Endoplasmic
Reticulum (ER). It is them esterified by two membrane-localized enzymes, acyl-CoA:
cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2), which are highly specific for
cholesterol and will not esterify plant sterols. About 70 to 80% of cholesterol entering the
Lymphatic system is esterified (Gropper, et al., 2009).