chapter 20
Lipids III: Plasma Lipoproteins
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
< 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
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
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