Positive linear correlation between the length of truncated apolipoprotein B and its secretion rate: in vivo studies in human apoB-89, apoB-75, apoB-54.8, and apoB-31 heterozygotes.

Apolipoprotein B (apoB), the major protein component of triglyceride-rich lipoproteins secreted from the liver, plays crucial roles in the secretion, transport, and receptor-mediated clearance of lipoproteins. A minority of cases of familial hypobetalipoproteinemia is due to genetically determined truncations of apoB-100 that range in size from apoB-9 to apoB-89, but truncated apoBs smaller than apoB-27.6 were not detected in plasma. To ascertain the physiologic bases of the hypobetalipoproteinemia, we studied in vivo metabolic parameters of the products of both the normal and mutant apoB alleles in human apoB truncation/apoB-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 endogenous labeling with [13C]leucine, mass spectrometry, and multicompartmental modeling. All truncated forms of apoB were secreted at reduced rates. The secretion rates of apoB-89, apoB-75, apoB-54.8, and apoB-31 were 92%, 64%, 37%, and 12%, respectively, of the respective apoB-100s on a molar basis. Additionally, particles containing apoB-89, apoB-75, and apoB-54.8 had increased fractional catabolic rates (FCR), while apoB-31-containing particles had a decreased FCR. On regression analysis, the secretion rate was linearly linked to the length of the truncated apoB (r2 = 0.86, P < 0.0001), with secretion being reduced by 1.4% for each 1% of apoB truncated. The linear regression line of apoB size 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 in 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.