Central Role of High Density Lipoprotein in Plasma Free Cholesterol Metabolism

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This study was designed to provide direct information on the in vivo metabolism in man of free (unesterified) cholesterol in the major lipoprotein classes. Five human subjects were administered one or two (simultaneous) of the following; [2-14C] mevalonic acid, high density lipoprotein (HDL)-free [14C] cholesterol, low density lipoprotein (LDL)-free [14C] cholesterol, and very low density lipoprotein (VLDL)-free [3H]cholesterol. Blood was then obtained at frequent intervals for at least 9 h, and the α(HDL) and β(LDL + VLDL) lipoproteins were quickly separated by heparin-manganese precipitation to prevent ex vivo exchange of free cholesterol. After the administration of [14C]mevalonic acid the specific activity (disintegrations per minute/micromole) of free cholesterol in the α- and β-lipoproteins increased for 3 h. During this period the α-free cholesterol specific activity was higher than the β specific activity. After administration of VLDL and LDL labeled with free cholesterol, the α-free cholesterol specific activity reached a peak value within 20 min, at which time it was considerably lower than the β-free cholesterol specific activity. When HDL labeled with free cholesterol was administered, a precursor product relationship was observed between the α-free cholesterol (precursor) and β-free cholesterol (product) specific activities.

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