Sitosterolemia and xanthomatosis together are a disease characterized by premature cardiovascular disease, and by elevated plasma concentrations of total sterols and of plant sterols, especially sitosterol which is hyperabsorbed. In order to determine whether this abnormal metabolism also involved other sterols, a patient with sitosterolemia was fed a diet high in shellfish that contain significant quantities of noncholesterol sterols, some of which are less well absorbed than cholesterol in humans. Compared with control subjects (n = 8), the sitosterolemic subject had an increased absorption of 22-dehydrocholesterol (71.5% vs. 43.8±11A%, mean±SD), C-26 sterol (80.6% vs. 493±11.4%), brassicasterol (51.8% vs. 4.8±4.2%), and 24-methylene cholesterol (60.5% vs. 16.0±8.3%). This enhanced absorption was associated with an increased plasma total shellfish sterol level (13.1 mg/dl vs. 1.9±0.7 mg/dl in normals). In the sitosterolemic subject, as in normals, the shellfish sterols were not preferentially concentrated in any lipoprotein class, and 50-65% of these sterols were in the esterified form in plasma. Bile acids and neutral sterols were quantitated in bile obtained by duodenal aspiration. The bile acid composition did not differ significantly in the sitosterolemic subject compared with the normal controls. The sitosterolemic subject, though, was unable to concentrate normally the neutral shellfish sterols in bile. The normal controls concentrated the shellfish sterols in bile 63±1.7-fold relative to the plasma shellfish sterol concentration whereas the study subject was only able to concentrate them 2.1-fold. We propose that sitosterolemia and xanthomatosis occur from a generalized abnormality in the usual ability of the gut mucosa and other tissues of the body to discriminate among many different sterols. This has important implications for the understanding of the pathophysiology of this disease and for therapeutic recommendations.

Freshly isolated human adipocytes showed specific uptake of 125I-labeled human high density lipoprotein (HDL2 and HDL3), a portion of which could be released by subsequent incubation with excess unlabeled ligand. To study the

Apo A-IMiu,. is a mutant form of apo A-I in which cysteine is substituted for arginine at amino acid 173. Subjects with apo A-IMih... are characterized by having low levels of plasma HDL cholesterol and apo A-I. To determine the kinetic etiology of the decreased plasma levels of the apo A-I in these individuals, normal and mutant apo A-I were isolated, radiolabeled with either 1251 or 131I, and both types of apo A-I were simultaneously injected into two normal control subjects and two subjects heterozygous for apo A-Im,.... In the normal subjects, apo A-IMil.. was catabolized more rapidly than the normal apo A-I (mean residence times of 5.11 d for normal apo A-I vs. 3.91 d for apo A-Imj.,,), clearly establishing that apo A-IMj,,.O is kinetically abnormal and that it has a shortened residence time in plasma. In the two apo A-Imi,. subjects, both types of apo A-I were catabolized more rapidly than normal (residence times ranging from 2.63 to 3.70 d) with normal total apo A-I production rates (mean of 10.3 vs. 10.4 mg/kg per d in the normal subjects). Therefore, in the subjects with apo A-Imo, the decreased apo A-I levels are caused by rapid catabolism of apo A-I and not to a decreased production rate, and the abnormal apo A-IMi,. leads to the rapid catabolism of both the normal and mutant forms of apo A-I in the affected subjects. (J. Clin.

The apolipoprotein E isolated from plasma of individuals with type III hyperlipoproteinemia (HLP) shows an abnormal pattern when it is examined by isoelectric focusing. Compared to apolipoprotein E from normal subjects, apolipoprotein E isolated from subjects with type III HLP had a decreased fractional catabolic rate in vivo in both type III HLP patients and normal individuals. The delayed catabolism of apolipoprotein E in type III HLP patients may be responsible for the lipid and lipoprotein abnormalities characteristic of these patients.