Page 89 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioChemistry

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Encyclopedia of Physical Science and Technology EN008C-380 June 29, 2001 16:42

656 Lipoprotein/Cholesterol Metabolism

FIGURE 12 The reverse cholesterol transport hypothesis. Extraheptatic cells accumulate cholesterol through the
uptake of LDL and modified forms of LDL through the LDL receptor, other members of the LDL receptor family, and/or
scavenger receptors. These cells efflux cholesterol and phospholipids to the extracellular milieu through a process
facilitated by a membrane transporter, ABC1. Free apo-A1 interacts with the phospholipid and cholesterol to form
HDL3 particles. LCAT esterifies the cholesterol to form discoidal HDL2 particles which then interact with the SR-B1
receptor at the surface of hepatocytes. Through that interaction, cholesterol esters are selectively taken up into the
hepatocytes and hydrolyzed. The free cholesterol is then secreted into the bile or converted to bile acids. Much of
this cholesterol is then excreted in the feces.

levels. However, under these circumstances, the transport tients with hypertriglyceridemia almost invariably have
of cholesterol to the liver is enhanced. When the diet is low HDL levels. The cholesterol ester transfer protein
shifted from saturated to polyunsaturated fat, HDL levels (CETP)-catalyzed transfer of cholesterol ester from HDL
typically drop. This drop is attributable to a rise in SR-B1 to VLDL occurs with reciprocal transfer of triglyceride to
expression in the liver. In short, a decrease in HDL can be HDL (Fig. 13). Lipoprotein lipase and hepatic lipase (an-
caused by imparied reverse cholesterol transport (extra- other cell-surface-bound lipase) catalyze the hydrolysis
hepatic; Tangier disease) or by increased reverse choles- of HDL triglyceride, reducing the size of the HDL par-
terol transport (liver; polyunsaturated fat). ticles. Hepatic lipase can also hydrolyze HDL phospho-
HDL metabolism is intimately connected with triglyc- lipids. Smaller HDL particles (HDL 3 ) are removed from
eride metabolism. Clinicians know this because pa- the circulation more quickly than larger HDL (HDL 2 ).