ORGAN LOCI OF CATABOLISM OF SHORT TRUNCATIONS OF APO-B

Truncations of apolipoprotein (apo) B shorter than 3200 amino acids (3 200/4536=apoB-70) do not possess the LDL receptor-recognition domain a nd are not recognized by altered cells with normally functioning LDL r eceptors. To ascertain which organs remove such truncated apoB-contain ing particles, we isolated apoB-31-, apoB-38.9-, and apoB-43.7-contain ing particles from plasmas of familial hypobetalipoproteinemia heteroz ygous humans by a combination of sequential ultracentrifugation and pr eparative electrophoresis, Particles with labeled I-125- or I-131-dila ctitol tyramine (I-DLT), were injected into New Zealand White rabbits, along with I-DLT-apoB-100-containing LDLs, and the decay of I-125- an d I-131-TCA-precipitated counts was followed over 24 hours. At the end of 24 hours, rabbits were anesthetized and their bodies perfused. Org ans were removed and homogenized, and TCA-precipitable counts determin ed, Fractional catabolic rates of apoB truncation particles were two t o five times greater than those of apoB-100 LDLs. ApoB truncations acc umulated in adrenals at one fifth the rates of apoB-100 LDL, compatibl e with the functional absences of LDL receptor-recognition domains in truncated apoBs. The major organ of uptake for apoB-100-LDLs was the l iver, 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 apo B-100 or truncation particles, suggesting particles were not ''damaged '' or aggregated. Thus, the absence of > 56% of the carboxyl end of ap oB-100 increases the plasma clearance and redirects the organ uptake o f the apoB truncation-containing lipoproteins from liver to kidney.