Animals absorb and transport large quantities of lipids.
A major challenge is posed by the solubility characteristics
of lipids. Because they are essentially insoluble in
water, they must be packaged in order to move through
an aqueous environment. Since many lipids are amphipathic
(have water-soluble and water insoluble moieties),
they have detergent-like properties that can be harmful to
Dietary cholesterol enters the intestinal lumen and is
solubilized in a bile acid micelle. Cholesterol is otherwise
quite insoluble in water (solubility limit ≈ 1 µg/liter).
The transport of lipids into the intestinal epithelial cells
requires their solubilization in bile acid micelles. First,
the solubilization facilitates the hydrolysis of fatty acid
ester bonds by the intestinal lipases. Second, the transport
into the enterocytes requires the formation of a properly
structured bile acid micelle.
Bile is comprised of three lipid components:
2., cholesterol, and
3. phosphatidylcholine (PC;
lecithin; Fig. 1).
An excess of cholesterol relative to the
two biliary amphipathic lipids (PC and bile acids) can lead
to the formation of cholesterol precipitates, more commonly
known as gallstones.
It is important to remember that ordinarily the major
component of dietary fat is always triglyceride
, not cholesterol
. For example, milk and butter have very little
cholesterol but are very high in triglyceride. Triglyceride
(and other glycerolipids, such as phospholipids) are hydrolyzed
in the intestinal lumen to yield monoglycerides
and free fatty acids. These lipolysis products are then absorbed
by the intestinal epithelial cells and resynthesized
Figure 1 The major lipid components
of bile. Bile acids are
and, together with phophatidylcholine and
cholesterol, form micelles in the intestinal
lumen. These micelles
solubilize lipids and
aid in their absorption by the intestinal
triglycerides, phospholipids, and cholesterol esters.
Thus, the intestine
mediates both lipolysis (in the lumen)
and re-esterification (within the epithelial cells) of dietary
The ability of the intestine to re-esterify monoglycerides
and cholesterol is essential for net lipid absorption.
This maintains a gradient that drives net lipid
absorption from the intestinal lumen. Indeed, pharmaceutical
companies have sought to develop inhibitors of
cholesterol absorption that function by inhibiting the intestinal
enzyme responsible for cholesterol esterification,
acyl-CoA:cholesterol acyltransferase (ACAT).
Although the intestine has a large capacity for lipid absorption
and esterification, it is not a lipid storage organ. It
must therefore package and export absorbed lipids in order
that they not accumulate. To accomplish this function,
the intestine assembles the lipids into specialized particles
called plasma lipoproteins