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.