Nutrition and Metabolism of Lipids 99Lipoprotein structure: a shopping bag
and groceries
The general structure of a lipoprotein consists of a
central core of hydrophobic, neutral lipid (TAG and
CE) surrounded by a hydrophilic coat of phospholip-
ids, free cholesterol, and apoproteins. A useful analogy
for this arrangement of molecules is that of a “shop-
ping bag and groceries,” with the lipid core represent-
ing the groceries and the outer coat the fabric of the
bag. The apoproteins weave in and out of the lipid
core and outer surface layer and form the thread of
the fabric which holds the bag together (see Figure
6.5). This clever arrangement of molecules renders
the hydrophobic lipids soluble for the purpose of
transport in blood. In addition to conferring struc-
tural integrity on the lipoprotein particle, apoproteins
have a vital role in controlling the metabolism of
lipoproteins by acting as ligands for cell membrane
receptors and cofactors for key enzymes.
Plasma lipoproteins can be subdivided into distinct
classes on the basis of their physical properties and/or
composition, both of which refl ect the physiological
role in the transport of lipids from sites of synthesis
(endogenous lipids) and absorption (exogenous
lipids, absorbed in the gut) to sites of storage (adipose
tissue) and utilization (skeletal muscle). The principal
classes of lipoproteins are traditionally defi ned by
density, which is determined by the ratio of lipid to
protein in the lipoprotein particle. Since lipids tend
to occupy a greater molecular volume than proteins,
they are lighter and less dense. Thus, particles with
high lipid content are larger and less dense (carry
more lipid groceries) than lipoproteins enriched with
protein. This property relates directly to the transport
function and metabolic interrelationships between
lipoprotein classes in blood. It can also be used to
separate lipoproteins of different densities because
lipoproteins of different density have different fl ota-
tion characteristics in the ultracentrifuge (note that
plasma lipoproteins will fl oat when subjected to cen-
trifugal force, whereas pure proteins sink). Other clas-
sifi cation schemes for plasma lipoproteins have
exploited differences in their net electrical charge
(electrophoretic mobility), particle size (exclusion
chromatography, gradient gel electrophoresis), and
immunological characteristics conferred upon
the lipoprotein by the types of apoproteins in each
lipoprotein subclass (see Table 6.4). Some of these
techniques permit the further resolution of VLDL,
low-density lipoproteins (LDLs), and high-density
lipoproteins (HDLs) into discrete subclasses, the dis-
tribution of which relates to cardiovascular risk and
is determined by genetic and lifestyle factors.Lipoprotein transport pathways
Lipoprotein transport can be described in terms of
the production, transport, and removal of cholesterol
or TAG from the circulation. In reality, these two
processes are inseparable because both TAG and cho-
lesterol are transported together in lipoproteins.
Lipoproteins are in a constant state of change, with
lipids and apoproteins constantly shuttling between
different lipoproteins that interrelate through inte-
grated metabolic pathways. A useful analogy here is
to think of lipoproteins as railway trains, transporting
passengers that represent lipids and apoproteins
within a complex rail network. The trains and
passengers are in a constant state of fl ux within
and between stations. Lipoprotein metabolism is con-
trolled by the activity of functional proteins (enzymes,
cell surface receptors, receptor ligands) that deter-
mine the rate at which lipoproteins enter and leave
the system, and by the physicochemical properties of
the lipoprotein themselves. This corresponds to all of
the rate-limiting features of a train journey, the
number of trains, and type of passengers.
All lipoproteins, with the notable exception of
HDLs, begin life as TAG-rich particles The principal
transport function of these lipoproteins in the fi rst
instance is to deliver fatty acids liberated from the
TAG to tissues. The enterocytes in the gut are the
producers of lipoproteins which deliver dietary fats
into the blood as chylomicrons (exogenous lipid),
whereas the liver is the central terminus for the pro-
duction of VLDLs and removal of their cholesterol-
rich end-products, LDLs. VLDLs, although smaller
than chylomicrons, resemble the latter in many ways
and are often referred to as the liver’s chylomicrons.
While the rate at which the gut produces chylomi-
crons depends largely on the amount of absorbed
dietary fat, the rate of production of VLDL is deter-
mined by the supply of fatty acids in the liver that can
be re-esterifi ed back to TAG for incorporation into
VLDL. These fatty acids are derived chiefl y from the
systemic circulation in the form of nonesterifi ed fatty
acids (NEFAs), and to a lesser extent from the uptake
of circulating lipoprotein remnants. It is noteworthy