432
chapter
2 0
Lipids III: Plasma Lipoproteins
Origin
P
1
ot2
a , *— Migration of
I
I
serum globulins
C athode
©
Anode
©
Chylom icrons
R-LP
Pre-ß-LP
(LDL)
(VLDL)
(Lp-a)
a-LP
(HDL)
F IG U R E 2 0 -2
Migration of plasma lipoproteins on paper electrophoresis at pH 8.6 in barbital buffer. LP = Lipoprotein; other
abbreviations as in Table 20-1.
stains (e.g., oil red O, fast red 7B, Sudan black B). Chy-
lomicrons appear at the origin (point of application of
the sample), VLDLs at the «
2
-region (the pre-fi region;
hence, “pre-/3 lipoproteins”), LDLs at the /
6
-globulin re-
gion (“/Mipoproteins”), and HDLs at the
a \
-globulin re-
gion (“a-lipoproteins”). The electrophoretic pattern of the
lipoproteins separated on paper (or on thin agarose films) is
shown in Figure 20-2, and a correlation of the classification
of lipoproteins by electrophoresis and hydrated density is
shown in Table 20-2.
As knowledge of the lipoproteins and of their physio-
logical roles has increased, the major species have been
subdivided. In the density class 1.006-1.063 g/mL, a
relatively pure LDL fraction may be isolated between
the densities of 1.019 and 1.063 g/mL. Lipoproteins
isolated in the
d
= 1.006-1.019
range are known as
intermediate-density lipoproteins
(IDLs
) and are thought
to represent VLDLs being processed to LDLs. The HDL
fraction is commonly subdivided into HDL
2
and HDL
3
.
HDL
2
occurs in the density range 1.063-1.125 g/mL
and HDL
3
at 1.125-1.21 g/mL. The composition of the
major and minor subclasses of lipoproteins is given in
Table 20-3.
Other lipoproteins are lipoprotein (a) and lipoprotein-
X. Lipoprotein (a) [Lp(a)j, a variant of LDL, occurs in the
plasma of normal subjects in the density range 1.040-
1.090 g/mL. Lp(a) is similar to LDL in lipid compo-
sition and also contains apo B-100, which is bound to
apolipoprotein (a) by a disulfide linkage. Apo(a) is a large
glycoprotein that exhibits size heterogeneity among indi-
viduals in a range of M.W. 300,000-800,000 on sodium
dodecyl sulfate (SDS-PAGE). On agarose electrophoresis,
Lp(a) migrates with VLDL (pre
- / 8
electrophoretic mobil-
ity). For this reason, it is also known as the “sinking pre-/
6
-
lipoprotein.” The anodal electrophoretic mobility of Lp(a)
relative to LDL may be due to its high content of sialic acid.
The exact physiological function of Lp(a) is not known.
However, apo(a) and plasminogen share extensive se-
quence homology. Both Lp(a) and plasminogen possess
multiple tandem repeats of triple loop structural motifs,
known as
kringles
(Chapter 36). Type 2 kringle IV is found
in apo(a) and varies from 11 to greater than 50 tandem re-
peats. The exact number of repeats is an inherited property
and defines different isoforms of Lp(a). The apo(a) gene is
close to the plasminogen gene (6q2.6-q2.7). Plasma Lp(a)
primarily arises in the liver.
T A B L E 2 0 -3
Composition o f Lipoproteins (percent o f mass)
Protein
Major Apoproteins
Phospholipid
Cholesterol
Cholesteryl
Ester
Triacylglycerol
Diameter
(nm)
Chylomicrons
2 (A-l, A-II, A-IV, B-48)
3
2
3
90
75-1200
VLDL
6
(B-100, C, E)
14
4
16
60
30-80
IDL
18 (B-100, E)
2 2
8
32
2 0
25-35
LDL
21 (B-100)
2 2
8
42
7
18-28
LP(a)
21 [B-100, apo (a)]
2 0
8
45
6
25-30
h d l
2
37 (A-I, A-II)
32
5
2 0
6
9-12
HDL
3
54 (A-I, A-II)
26
2
15
3
5-9
*Represents the sum of both free and esterified cholesterol.
