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Sources of HDL. HDL is derived from
production in the intestinal mucosa and liver, as well as from breakdown
of chylomicrons and possibly VLDL. Nascent HDL is discoidal when first formed and becomes spherical in plasma as
the formation and storage of cholesteryl ester in its cores (via LCAT) lowers the surface-to-volume ratio. Nascent
chylomicrons pick up apo C from plasma HDL, which serves to hinder chylomicron uptake by the liver. After losing a
substantial portion of their triacylglycerols to peripheral tissues via lipoprotein lipase, chylomicrons recycle most of
their apo C back to HDL, and then gain apo E, which mediates their hepatic uptake as chylomicron remnants.
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Role of HDL in peripheral cholesterol removal. Free cholesterol in plasma membranes of peripheral tissues is
transferred to apo A-I containing pre-/l-HDL (nascent HDL), via an ATP-binding cassette transporter 1 (ABC1).
Cholesterol is esterified by LCAT and stored in the core of the HDL particle. In the presence of suitable acceptor
lipoproteins (VLDL or LDL), cholesteryl esters are transferred from HDL via apo D and CETP to the lower density
lipoproteins, thereby shortening the half-life of plasma cholesterol since VLDL and LDL have a much faster turnover
time than HDL. PL = Phospholipid.