The Metabolism of Truncated Forms of Apolipoprotein B in Hypobetalipoproteinemia

Abstract

In recent years explanations have been found for the very low levels of total- and LDL-cholesterol seen in some humans (Young, 1990). In addition to patients with “classical” abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease whose total plasma cholesterol levels approximate 40 mg/dl (~ 1mM) and who may suffer from the consequences of severe fat malabsorption (Herbert et al., 1985; Huang et al., 1991; Pessah et al., 1991), there are persons whose total plasma cholesterols are of the order of 100–120 mg/dl (~ 2.5–3.0mM, <5th percentile for age and sex) and who appear to be in good health. Indeed, some affected individuals may attain very long lifespans. We now know that many of these cases of uncomplicated hypobetalipoproteinemia are associated with genetically determined truncations of apoB-100, (the major apolipoprotein of LDL), and that the low LDL levels are due to alterations in the metabolism of the truncated apoB-containing lipoprotein particles.