Page 78 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioChemistry

P1: GNH Final Pages
Encyclopedia of Physical Science and Technology EN008C-380 June 29, 2001 16:42

Lipoprotein/Cholesterol Metabolism 645

Although the intestine has a large capacity for lipid ab-
sorption and esterification, it is not a lipid storage organ. It
must therefore package and export absorbed lipids in or-
der that they not accumulate. To accomplish this function,
the intestine assembles the lipids into specialized particles
called plasma lipoproteins.

II. PLASMA LIPOPROTEIN STRUCTURE

Plasma lipoproteins are uniquely endowed with the abil-
ity to transport large quantities of water-insoluble lipids
through an aqueous environment. This because the non-
FIGURE 1 The major lipid components of bile. Bile acids are polar lipids (triglyceride and cholesterol ester; Fig. 2) are
effective detergents and, together with phophatidylcholine and “buried” in the core of the lipoprotein, surrounded by a
cholesterol, form micelles in the intestinal lumen. These micelles
monolayer of amphipathic lipids, phospholipid, and unes-
solubilize lipids and aid in their absorption by the intestinal mu-
terified cholesterol (Fig. 3).
cosal cells.
In addition to core and surface lipids, lipoproteins carry
proteins termed apolipoproteins (Tables III and IV). These
Dietary cholesterol enters the intestinal lumen and is
proteins stabilize the lipoprotein particles and carry out
solubilized in a bile acid micelle. Cholesterol is otherwise
particular functions such as receptor recognition and acti-
quite insoluble in water (solubility limit ≈ 1 µg/liter).
vation of particular enzymes.
The transport of lipids into the intestinal epithelial cells
Lipids are less dense than water. Consequently, because
requires their solubilization in bile acid micelles. First,
they are complexed with lipid, plasma lipoproteins tend
the solubilization facilitates the hydrolysis of fatty acid
to float when plasma is subjected to ultracentrifugation
ester bonds by the intestinal lipases. Second, the transport
(Table I). In contrast, other blood proteins sediment in the
into the enterocytes requires the formation of a properly
centrifuge. Lipoproteins float at distinct buoyant densi-
structured bile acid micelle.
ties and are named according to their flotation behavior.
Bile is comprised of three lipid components: (1) bile
The lipoprotein classes are (Table II) chylomicrons, very-
acids, (2), cholesterol, and (3) phosphatidylcholine (PC;
low density lipoprotein (VLDL), low density lipoprotein
lecithin; Fig. 1). An excess of cholesterol relative to the
(LDL), and high density lipoprotein (HDL). Chylomicrons
two biliary amphipathic lipids (PC and bile acids) can lead
and VLDL are primarily triglyceride carriers, while LDL
to the formation of cholesterol precipitates, more com-
and HDL are primarily cholesterol (mostly cholesterol
monly known as gallstones.
ester) carriers.
It is important to remember that ordinarily the ma-
jor component of dietary fat is always triglyceride, not
Key Points about the Distribution
cholesterol. For example, milk and butter have very little
of Apolipoproteins
cholesterol but are very high in triglyceride. Triglyceride
(and other glycerolipids, such as phospholipids) are hy- Only HDL has no apo-B.
drolyzed in the intestinal lumen to yield monoglycerides For practical purposes LDL can be considered to have
and free fatty acids. These lipolysis products are then ab- only apo-B.
sorbed by the intestinal epithelial cells and resynthesized The other apolipoproteins overlap and, as described
as triglycerides, phospholipids, and cholesterol esters. below, readily transfer between the various lipoprotein
Thus, the intestine mediates both lipolysis (in the lumen) particles while circulating in the bloodstream.
and re-esterification (within the epithelial cells) of dietary
lipids. It is useful to make a distinction between exogenous
The ability of the intestine to re-esterify monoglyc- and endogenous lipid transport. Exogenous lipid transport
erides and cholesterol is essential for net lipid absorp- refers to dietary fat. Endogenous lipids are those synthe-
tion. This maintains a gradient that drives net lipid sized by the liver and adipose tissue from substrates that
absorption from the intestinal lumen. Indeed, pharma- have already been absorbed and metabolized in these tis-
ceutical companies have sought to develop inhibitors of sues. The exogenous pathway refers to the absorption of
cholesterol absorption that function by inhibiting the in- lipids in the intestine and the metabolism of chylomicrons.
testinal enzyme responsible for cholesterol esterification, Lipids from chylomicrons can eventually mix with the en-
acyl-CoA:cholesterol acyltransferase (ACAT). dogenous lipid pools in the liver and adipose tissue.