PubMed1997
Truncations of apolipoprotein (apo) B shorter than 3200 amino acids (3200/4536 = apoB-70) do not possess the LDL receptor-recognition domain and are not recognized by altered cells with normally functioning LDL receptors. To ascertain which organs remove such truncated apoB-containing particles, we isolated apoB-31-, apoB-38.9-, and apoB-43.7-containing particles from plasmas of familial hypobetalipoproteinemia heterozygous humans by a combination of sequential ultracentrifugation and preparative electrophoresis. Particles with labeled 125I- or 131I-dilactitol tyramine (I-DLT), were injected into New Zealand White rabbits, along with I-DLT-apoB-100-containing LDLs, and the decay of 125I- and 131I-TCA-precipitated counts was followed over 24 hours. At the end of 24 hours, rabbits were anesthetized and their bodies perfused. Organs were removed and homogenized, and TCA-precipitable counts determined. Fractional catabolic rates of apoB truncation particles were two to five times greater than those of apoB-100 LDLs. ApoB truncations accumulated in adrenals at one fifth the rates of apoB-100 LDL, compatible with the functional absences of LDL receptor-recognition domains in truncated apoBs. The major organ of uptake for apoB-100-LDLs was the liver, whereas truncation particles were readily removed by the kidney (kidney: liver uptake ratios were 0.10 to 0.30 for apoB-100 LDLs and 1.03 to 3.77 for truncations). Spleens accumulated little of either apoB-100 or truncation particles, suggesting particles were not "damaged" or aggregated. Thus, the absence of > 56% of the carboxyl end of apoB-100 increases the plasma clearance and redirects the organ uptake of the apoB truncation-containing lipoproteins from liver to kidney.