Food Lipids: Chemistry, Nutrition, and Biotechnology

educe the risk of coronary heart disease and promote the regression of atherosclerotic
lesions [40,41]. The total exchangeable cholesterol of the human body is estimated
at 60 g for a 60-kg man. The cholesterol turnover rate is in the order of 0.8–
1.4 g/day. Both the dietary uptake and the biosynthesis contribute significantly to
body cholesterol. In Western countries the daily ingestion of cholesterol ranges from
0.5 to 3.0 g, although only a portion of this sterol is absorbed from the intestine.
The absorption of dietary cholesterol ranges from 25% (high dietary sterol intake)
to 50% (low dietary sterol intake). The total body cholesterol level is determined by
the interaction of dietary cholesterol, the excretion of cholesterol and bile acid, and
the biosynthesis of cholesterol in tissue.
The major site of cholesterol synthesis in mammals is the liver. Appreciable
amounts of cholesterol are also formed by the intestine. The rate of cholesterol
formation by these organs is highly responsive to the amount of cholesterol absorbed
from dietary sources. This feedback regulation is mediated by changes in the activity
of HMG-CoA reductase. As discussed in connection with pathway for the biosynthesis
of cholesterol, this enzyme catalyzes the formation of mevalonate, which is
the committed step in cholesterol biosynthesis. Dietary cholesterol suppresses cholesterol
biosynthesis in these organs through the regulation of HMC-CoA reductase
activity. In 1974, Kandutsch and Chen observed that highly purified cholesterol (in
contrast to crude cholesterol) is rather ineffective in lowering HMG-CoA reductase
activity in culture cells [37]. This perception led to the recognition that oxidized
derivatives of sterols (oxysterols), rather than cholesterol, may function as the natural
regulators of HMG-CoA reductase activity. Furthermore, oxysterols display a high
degree of versatility ranging from substrates in sterol biosynthesis to regulators of
gene expression to cellular transporters.
Cholesterol, triacylglycerols, and other lipids are transported in body fluids to
specific targets by lipoproteins. A lipoprotein is a particle consisting of a core of
hydrophobic lipids surrounded by a shell of polar lipids and apoproteins. Lipoproteins
are classified according to their densities. LDL, the major carrier of cholesterol
in blood, has a diameter of 22 nm and a mass of about 3 � 10 6 daltons (Da). LDL
is composed of globular particles, with lipid constituting about 75% of the weight
and protein (apoprotein B) the remainder. Cholesterol esters (about 1500 molecules)
are located at the core, which is surrounded by a more polar layer of phospholipids
and free cholesterol. The shell of LDL contains a single copy of apoprotein B-100,
a very large protein (514 kDa). The major functions of LDL are to transport cholesterol
to peripheral tissues and to regulate de novo cholesterol synthesis at these sites.
As we discussed above, the major site of cholesterol biosynthesis is the liver.
The mode of control in the liver has also been discussed: dietary cholesterol (possibly
oxysterols) reduces the activity and amount of HMG-CoA reductase, the enzyme
catalyzing the committed step of cholesterol biosynthesis. In some tissues, such as
adrenal gland, spleen, lung, and kidney, biosynthesis contributes only a relatively
small proportion of the total tissue cholesterol, with the bulk being derived by uptake
from LDL in the blood. Investigation upon the interaction of plasma LDL with
specific receptors on the surface of some nonhepatic cells has led to a new understanding
of the mechanisms of cellular regulation of cholesterol uptake, storage, and
biosynthesis in peripheral tissues.
Michael Brown and Joseph Goldstein did pioneering work concerning the control
of cholesterol metabolism in nonhepatic cells based on studies of cultured human
Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.