The early metabolism of cell-derived cholesterol was followed during the interaction of normolipaemic native plasma with cultured cell monolayers labelled to high specific activity with 3H-cholesterol. Kinetic analysis indicated that initial processing involved several prebeta-migrating high-density lipoprotein (HDL) species. A small prebeta species, the initial acceptor, was first converted to a lipoprotein whose composition predicts a discoidal structure. The free cholesterol content of this was then esterified by lecithin: cholesterol acyltransferase, and its cholesterol converted to the alpha mobility of spheroidal mature HDL the binding of apolipoprotein A-II. These studies follow the genesis of HDL in plasma from peripheral cell membrane cholesterol.
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