Investigation of Serum Lipoproteins and Apoproteins in Abetalipoproteinaemia

Abstract

1. The serum lipoproteins, apoproteins and lecithin-cholesterol acyltransferase activity of three patients with abetalipoproteinaemia have been studied.2. Concentration of lipoproteins with a density of less than 1-063 was found to be 5-6 mg/lOO ml of plasma. The protein part consisted only of apoAI polypeptides.3. Concentration of total serum high-density lipoproteins was 90-100 mg/lOO ml. After total delipidization of this fraction, apoproteins were separated by column chromatography. All apoA and most of the apoC peptides could be demonstrated by immunochemical methods and polyacrylamide gel electrophoresis.4. Quantification of individual polypeptides indicated that the proportions apoAI : apoAII :apoAIII in high-density lipoproteins were not different from those observed in normal subjects. ApoCIII, was absent in the patients' serum. In the remaining apoC peptides differences in the distribution compared with normal subjects could be demonstrated. 5.With antibodies to lipoprotein B, acetylated lipoprotein B or apolipoprotein B no reaction could be observed with abetalipoproteinaemic serum or any density fraction tested including density 1.23 infranate.6. Isoelectric focussing of prestained lipoproteins in complete patients' serum revealed the absence of four major lipoprotein families present in normal serum.7. Lecithin-cholesterol acyltransferase activity of abetalipoproteinaemic serum was reduced to a value of about 50% of normal but lipoproteins of patients' serum could be utilized as a substrate only to a minor degree. The maximum activity was observed only if lipoproteins of normal serum were added to the assay system.

Regulation of low density lipoprotein receptors by plasma lipoproteins from patients with abetalipoproteinemia.

“…The lipoprotein particles present in the HDL fraction of abetalipoproteinemic plasma have an unusual density distribution, with an HDL2 to HDL3 ratio of 3:1 (29)(30)(31)(32). Although the apoprotein composition of HDL has not been fully characterized, two distinctive features appear to be a virtual absence of apoprotein GIll-1 (29,31,32) and a relative enrichment in apoprotein E (32-34, §).…”

“…Although the apoprotein composition of HDL has not been fully characterized, two distinctive features appear to be a virtual absence of apoprotein GIll-1 (29,31,32) and a relative enrichment in apoprotein E (32-34, §). Blum et al (33) Receptor-mediated uptake of LDL has been shown to be of greatest importance in tissues that actively synthesize and secrete steroid hormones (36)(37)(38): If the HDL2 particles present in the plasma of patients with abetalipoproteinemia are able to fully substitute for LDL, then it would be anticipated that maximal rates of steroid hormone production would be normal in these patients.…”

Normotriglyceridemic abetalipoproteinemia. absence of the B-100 apolipoprotein.

“…In that disorder, normal chylomicrons, very low density lipoproteins (VLDL),1 and low density lipoproteins (LDL) are absent from plasma. A small amount of an abnormal lipoprotein, which can be concentrated from the low density untracentrifugal interval, appears to be derived from high density lipoproteins (HDL) (1)(2)(3)(4). Clinical features include severe malabsorption of triglycerides (5), acanthocytosis of erythrocytes (often with autohemolysis) (1,6), de-ficiency of tocopherols and often other fat soluble vitamins in plasma, retinopathy (7), and progressive neurological disease (1).…”

High Density Lipoprotein Metabolism in a Patient with Abetalipoproteinemia

“…Although apoprotein B is not a constituent of high density lipopro teins (HDL) the concentration of this lipo protein is also reduced in abetalipoproteinemia. The lipoprotein particles present in the HDL fraction of abetalipoproteinemic plasma have an unusual density distribution with a HDL2:HDL3 ratio of 3:1 (3)(4)(5). Under electron microscopy these HDL particles ap pear similar to normal HDL.…”