Organ loci of catabolism of short truncations of apoB.
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.
Zhu
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XF
Division of Atherosclerosis, Nutrition, and Lipid Research, Washington University School of Medicine, St Louis, Mo 63110, USA.
Noto
D
D
Seip
R
R
Shaish
A
A
Schonfeld
G
G
D000328:Adult; D000368:Aged; D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D011817:Rabbits; D014018:Tissue Distribution
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B