POSITIVE LINEAR CORRELATION BETWEEN THE LENGTH OF TRUNCATED APOLIPOPROTEIN-B AND ITS SECRETION RATE - IN-VIVO STUDIES IN HUMAN APO-B-89, APO-B-75, APO-B-54.8, AND APO-B-31 HETEROZYGOTES

Apolipoprotein B (apoB), the major protein component of triglyceride-r ich lipoproteins secreted from the liver, plays crucial roles in the s ecretion, transport, and receptor-mediated clearance of lipoproteins. A minority of cases of familial hypobetalipoproteinemia is due to gene tically determined truncations of apoB-100 that range in size from apo B-9 to apoB-89, but truncated apoBs smaller than apoB-27.6 were not de tected In plasma. To ascertain the physiologic bases of the hypobetali poproteinemia, we studied in vivo metabolic parameters of the products of both the normal and mutant apoB alleles in human apoB truncation/a poB-100 heterozygotes (apoB-89/apoB-100, n = 2, apoB-75/apoB-100, n = 2; apoB-54.8/apoB-100, n = 6; apoB-31/apoB-100, n = 1) using endogenou s labeling with [C-13]leucine, mass spectrometry, and multicompartment al modeling. All truncated forms of apoB were secreted at reduced rate s. The secretion rates of apoB-89, apoB-75, apoB-54.8, and apoB-51 wer e 92%, 64%, 37%, and 12%, respectively, of the respective apoB-100s on a molar basis. Additionally, particles containing apoB-89, apoB-75, a nd apoB-54.8 had increased fractional catabolic fates (FCR), while apo B-31-containing particles had a decreased FCR. On regression analysis, the secretion rate was linearly linked to the length of the truncated apoB (tau(2) = 0.86, P < 0.0001), with secretion being reduced by 1.4 % for each 1% of apoB truncated. The linear regression line of apoB si ze versus apoB secretion rate has a zero intercept for apoB secretion at apoB-28, which is consonant with the apparent absence in plasma of truncations smaller than apoB-25. We conclude that secretion of apoB i n vivo is dependent on the length of the truncation of apoB, possibly because the smaller the truncated apoB, the less it is protected from intracellular degradation.-Parhofer, K. G., P. H. R. Barrett, C. A. Ag uilar-Salinas, and G. Schonfeld. Positive linear correlation between t he length of truncated apolipoprotein B and its secretion rate: in viv o studies in human apoB-89, apoB-75, apoB-54.8, and apoB-31 heterozygo tes.