Studies on the Protein Defect in Tangier Disease

Abstract

A B S T R A CT High density lipoproteins (d 1.063-1.210 g/ml) were isolated from the plasma of normal individuals (HDL) and seven homozygous patients with Tangier disease (HDLT). In Tangier patients., the concentration of protein in the high density region (HDLT) was only 0.5-4.5% of normal. Immunochemical studies, including mixing experiments conducted in vivo and in vitro, indicated that HDLT was different from HDL. HDLT was the only high density lipoprotein detectable in the plasma of Tangier homozygotes. In heterozygotes both HDL and HDLT were present. HDLT was not detected in the plasma of over 300 normal persons and 10 patients with secondary high density lipoprotein deficiency and appeared to be a unique marker for Tangier disease.ApoHDL contained two major apoproteins designated apoLp-Gln-I and apoLp-Gln-II; together they comprised 85-90% of the total protein content. Both of the major HDL apoproteins were present in apoHDLT; but apoLp-Gln-I was disproportionately decreased with respect to apoLp-Gln-II, the ratio of their concentrations being 1: 12 in apoHDLT as compared with 3: 1 in apoHDL. Several minor apoprotein components which together comprise 5-15% of apoHDL were present in approximately normal proportions in apoHDLT. In the HDL of Tangier patients it was estimated that, compared with normal individuals, the concentration of apoLp-Gln-I was decreased about 600-fold and the con-

The Structure of Human High Density Lipoprotein and the Levels of Apolipoprotein A-I in Plasma as Determined by Radioimmunoassay

“…However, reasonable agreement exists between the immunologic and physical methods. In addition, the ApoA-I levels obtained here are not too different from those obtained by direct analysis of isolated HDL fractions (36) and by another RIA recently reported in abstract form (16). The assay, therefore, represents a distinct improvement over available methods.…”

“…The apparent ApoA-I concentrations of untreated plasmas ranged from 4.8-14.4 mg/dl in assays using ApoA-I standards. These results were considerably lower than expected (36). Therefore, plasmas were extracted with ether-ethanol and treated with urea as described above for HDL.…”

A molecular theory of lipid—protein interactions in the plasma lipoproteins

“…From previous studies [1][2][3] it seems reasonable to assume that the interactions between phospholipids and lipoprotein-protein (apoprotein) constituents are fundamental to the binding of neutral lipid by the plasma lipoproteins. For example, there is an insignificant binding of cholesteryl ester by the apoproteins of human HDL * in the absence of phospholipids.…”

13 C Nuclear Magnetic Resonance Spectroscopic Evidence for Hydrophobic Lipid-Protein Interactions in Human High Density Lipoproteins

“…HDL and apoHDL were obtained by established procedures (23,24). The two main fractions, apoA-I and apoA-II, were isolated by DEAE-cellulose chromatography (25) in a homogeneous form, as shown by polyacrylamide gel electrophoresis (26) and by immunoprecipitation (antisera were kindly provided by Dr. Greten, Medizinische Klinik, Heidelberg). The amino-acid composition of the two proteins compared well with those published (24,27).…”