The Ultrastructure of Plasma Lipoproteins in Lecithin: Cholesterol Acyltransferase Deficiency

Abstract

The major plasma lipoprotein classes from patients with familial LCAT deficiency showed morphological abnormalities. Very low density lipoproteins (VLDL) contained particles with surface irregularities as well as sheet-like trilaminar structures which resembled phospholipid bilayers. Three types of particles were seen in the low density (LDL) region, large flattened structures approximately 1, 000A in size, intermediate particles 400–600A in diameter, and normal 200–250A particles. The high density lipoproteins (HDL) were characterized by discoidal particles 40A thick and 150–200A in diameter; these particles formed rouleaux. Abnormal HDL particles could be normalized by incubation of whole LCAT-deficient plasma (or HDL fraction) with LCAT; resulting structures resembled normal HDL (90–110A spheres). In severe liver disease with apparent biliary obstruction the structure of plasma lipoproteins often resembled those of familial LCAT deficiency. Rouleaux, consisting of disc-shaped particles, were in the HDL fraction, and these structures were also normalized by incubation with LCAT. Reassembly studies with apolipoproteins plus phospholipid suggested that the discs represent a bilayer structure stabilized by protein. Cholesteryl ester incorporated into the protein-lipid complex produced spherical particles.