Turnover and tissue distribution of 125-I-labeled low density lipoprotein in swine and dogs.

Swine plasma low density lipoprotein (LDL) isolated ultracentrifugally (d 1.019-1.063) was labeled with 125-I, dialyzed, and reisolated by centrifugation at d 1.063. Over 96% of the radioactivity was shown to be associated with the apoprotein. After reinjection into the donor animal, disapperance of 125-I was followed for up to 122 hr. At all time intervals examined, over 95% of the total plasma 125-I was recovered in LDL (D 1.006-1.063), i.e., there was apparently no transfer of radioactivity to high density or very low density lipoproteins. The disappearance curve was biexponential, with half-lives of 0.83 plus or minus 0.06 and 22.5 plus or minus 1.7 hr for the first and second phases, respectively (13 studies). The mean calculated fractional catabolic rate was 0.041 plus or minus 0.003 hr-minus 1. Similar results were obtained in three dogs using autologous LDL of density 1.020-1.050; fractional catabolic rates were 0.031, 0.031, and 0.029 hr-minus 1. Tissue distribution of 125-I was determined in swine killed at various time intervals after [125-I]LDL injection with corrections for radioactivity in trapped plasma. Of the tissues examined, the liver showed by far the highest concentration. Total hepatic radioactivity, expressed as a percentage of total plasma radioactivity, was rather constant and independent of the time of killing from 3 to 122 hr (15.8 plus or minus 1.9%). The total extravascular LDL pool calculated from analysis of the plasma disappearance curves was about 20-30% of the size of the plasma LDL pool. These data are consistent with the conclusion that the liver accounts for a very large fraction of the total extravascular LDL pool. These data are consistent with the conclusion that the liver accounts for a very large fraction of the total extravascular LDL pool and that it is infairly rapid equilibrium with the plasma pool. To what extent the liver is involved in irreversible degradation cannot be inferred from these findings.