Biology of Disease

in the form of very low density lipoproteins (VLDL). These contain the
apolipoprotein, B-100, but the major lipids are triacylglycerols, with less
than 20% free cholesterol and cholesteryl esters (Table 14.1). A primary
determinant of the amount of VLDL secreted is the amount of free fatty
acids entering the liver. Further, if saturated fatty acids predominate, the
VLDL particles are smaller but more numerous than if polyunsaturated fatty
acids are in excess. A high carbohydrate diet also substantially increases
the concentration of plasma VLDL particles. Newly secreted VLDL particles
undergo a series of changes in the plasma. They acquire apoC and apoE
proteins from high density lipoproteins (HDL, see below). The catalyzed
hydrolysis of triacylglycerols by lipoprotein lipase of the endothelial cells
of capillaries allows the fatty acids and glycerol to be taken up by tissues.
The reduced triacylglycerol content increases the density of the VLDL so
that they become low density lipoproteins (LDL), and these particles are
the principal carriers of cholesterol in the plasma. Low density lipoprotein
particles serve as the major source of cholesterol for most of the tissues.
Although most cells can synthesize cholesterol, the bulk of synthesis occurs
in the liver and intestinal enterocytes.

The concentration of LDL in the plasma correlates positively with the
incidence of coronary heart disease. Hence LDL is often referred to as ‘bad’
cholesterol. However, it is only ‘bad’ in excess, and when combined with
other risk factors. High density lipoproteins are secreted by the liver, but they
are also formed by modifications to chylomicrons and VLDL. High density
lipoproteins (Table 14.1) can pick up cholesterol from tissues, essentially the
opposite function to that of LDL. The particles probably acquire cholesterol
from the cell surface membranes and convert it enzymatically to cholesteryl
esters. Consequently HDL may be considered ‘good’ cholesterol.

ATHEROSCLEROSIS OR ARTERIOSCLEROSIS

CZhhVg6]bZY!BVjgZZc9Vlhdc!8]g^hHb^i]:YLddY )%(

GIT

TAG

TAG

TAG

TAG

VLDL

(IDL)

ApoE receptor

LDL

receptor

LDL receptor

Chylomicrons

LDL

Peripheral

tissues

Liver

Figure 14.15 Schematic illustrating the transport

of cholesterol. IDL, intermediate density

lipoprotein particle; LDL, low density lipoprotein

particle; VLDL, very low density lipoprotein

particle; TAG, triacylglycerols. See text for details.

Chylomicrons VLDL LDL HDL

Density/gcm-3 0.93 <1.006 1.019-1.063 1.063-1.21

Protein / % 2 9 20 45

Phospholipid / % 8 20 20 25

Free cholesterol / % 1 7 10 5

Triacylglycerols / % 85 55 10 8

Cholesteryl esters / % 2 10 35 15

Apolipoproteins B-48, C, E A, B-100, C, E B-100 A, C, D, E

Table 14.1Composition of lipoprotein particles