A B S T R A C T This study was designed to provide direct information on the in vivo metabolism in man of free (unesterified) the a-and fB-lipoproteins increased for 3 h. During this period the a-free cholesterol specific activity was higher than the ,B specific activity. After administration of VLDL and LDL labeled with free cholesterol, the a-free cholesterol specific activity reached a peak value within 20 min, at which time it was considerably lower than the 13-free cholesterol specific activity. When HDL labeled with free cholesterol was administered, a precursor product relationship was observed between the a-free cholesterol (precursor) and ,3-free cholesterol (product) specific activities.A multicompartmental model was developed that contained the simplest structure necessary to fit all of the data obtained. The kinetic analysis revealed the presence of extensive exchange (20-85 ,umol/min) of free cholesterol between HDL and a tissue pool(s) enriched with newly synthesized free cholesterol. It was found that virtually all (>95%) of the free cholesterol

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