title: Metabolism of apolipoprotein B-100 in a kindred with familial hypobetalipoproteinemia without a truncated form of apoB.
abstract: Familial hypobetalipoproteinemia (FHBL) exists in three forms: a) FHBL genetically linked to truncated forms of apolipoprotein B (apoB); b) FHBL linked to the apoB gene but with no apoB truncations; and c) FHBL not linked to the apoB gene. Mean production rate (PR) of apoB-100 in FHBL subjects heterozygous for apoB truncations is approximately 30% of normal. In a 49-member D-kindred (FHBL phenotype defined as apoB < 40 mg/dl), no apoB truncations were detectable either by immunoblotting of plasma or by sequencing of relevant stretches of the apoB gene. Herein we report on the kinetic parameters of apoB-100-containing lipoproteins in four affected members of the D-kindred, and compare their kinetic values to 14 normal subjects, and 8 previously reported FHBL subjects heterozygous for various truncated forms of apoB. After an 8-h primed intravenous infusion of [13C]-leucine, enrichments of apoB-100 were assessed by gas chromatography-mass spectrometry and kinetic parameters were calculated by multicompartmental modeling. The affected members of the D-kindred had similar very low, intermediate, and low density lipoprotein (VLDL, IDL, and LDL) PRs as normal controls, but their fractional catabolic rates (FCR) for VLDL and LDL were approximately 2 and 3 times higher, respectively, than those of normals. By contrast in apoB truncation subjects, apoB-100 PRs were uniformly reduced, while apoB-100 FCRs were similar to normals. Thus, diverse physiologic mechanisms are responsible for the low apoB levels in these two different, genetically determined forms of FHBL.
authors.affiliation: Washington University School of Medicine, Department of Internal Medicine, St. Louis, MO 63110-1093, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Latour
authors.forename: B W
authors.initials: BW
authors.lastname: Patterson
authors.forename: J
authors.initials: J
authors.lastname: Pulai
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Schonfeld
mesh_terms: D000293:Adolescent; D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000097:blood; D002850:Chromatography, Gel; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007009:Hypolipoproteinemias / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008297:Male; D008954:Models, Biological
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008055:Lipids; D008074:Lipoproteins; D002784:Cholesterol