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 flux 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 first 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-esterified back to TAG for incorporation into VLDL. These fatty acids are
derived chiefly from the systemic circulation in the form of nonesterified
fatty acids (NEFAs), and to a lesser extent from the uptake of circulating
lipoprotein remnants. It is noteworthy that, although the liver has the
capacity to synthesize fatty acids, the amount synthesized by de novo lipo-genesis is relatively small
in humans on a mixed Western diet. However, the contribution of fatty acids
from this source may increase in conditions associ-ated with an overproduction
of VLDLs, and has been shown to occur on low-fat, high-carbohydrate diets, and
in metabolic disease.
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Introduction to Human Nutrition: Nutrition and Metabolism of Lipids : Lipoprotein transport pathways - Circulating lipids: lipoprotein structures and metabolism |