430

chapter 20

Lipids III: Plasma Lipoproteins

FIGURE 20-1

Generalized structure of a lipoprotein molecule showing the distribution of polar components in an outer shell composed

of free cholesterol, phospholipids, and amphipathic proteins and in an inner core composed of neutral triacylglycerols

and cholesteryl esters. Phospholipids are oriented with polar head groups toward the aqueous environment and

hydrophobic tails toward the neutral core, analogous to their positioning in the outer leaflet of the typical cell membrane.

These four major groups of plasma lipoproteins can

be separated and characterized by electrophoresis and ul-

tracentrifugation (Table 20-2). Each group is heteroge-

neous and can be subdivided on the basis of variation in

apoprotein and lipid compositions. The groups share sev-

eral apoprotein components, e.g., apo B occurs in chy-

lomicrons, LDLs, and VLDLs. Some apoproteins belong

to families of polypeptides, one or another of which may

predominate in a particular lipoprotein group. For exam-

ple, apo B, when formed in chylomicrons synthesized in

intestinal mucosa, is apo B-48, while that in VLDL from

the liver is B-100. The designations B-48 and B-100 re-

flect the relative molecular masses of these proteins, B-48

being 48% of the mass of B-100. Intestinal apo B contains

2152 of the 4563 amino acids that make up the hepatic

form. Oligonucleotide hybridization studies have shown

the intestinal and hepatic genes to be identical. The short-

ened intestinal form of apo B is produced by a single

nucleotide substitution of uracil for cytosine at position

6457 in the nucleotide sequence of the apo B mRNA. This

changes the codon CAA (glutamine) to the termination

codon UAA. The tissue-specific apo B mRNA editing,

which consists of site-specific deamination of cytosine to

uracil, is mediated by a multicomponent cytidine deami-

nase. This unique form of mRNA editing eliminates the

carboxy terminal portion of apo B to form the B-48 of

chylomicrons. Since the carboxy terminal portion of the

apo B sequence contains the apo B-binding domain, this

deletion ensures a distinct metabolic routing of the chy-

lomicron particle.

In a tube of plasma or serum collected from a nonfast-

ing individual and allowed to stand overnight, chylomi-

crons collect at the top surface in a milky layer because

of their low density

(d

< 0.95). If a pure sample of chy-

lomicron is required, it is better to obtain it from lymph

or to separate VLDLs from chylomicrons in plasma by

chromatography. Sequential ultracentrifugation is used to

obtain various lipoprotein fractions from a single sample.

Ultracentrifugation of fasting serum or plasma at its own

density (1.006) for 18 hours at

1 0 0 , 0 0 0

x

g

will float the

VLDL fraction

(d <

1.006). After removal of the VLDL,

the density of the remaining serum is raised to 1.063 and