In the following report, cynomolgous monkeys, fed atherogenic diets containing either saturated, monounsaturated, polyunsaturated (n-6 Poly) or fish oil (n-3 Poly) fat as 35% of total calories, provide a model for the study of dietary fat effects on plasma lipoproteins and atherosclerosis. We have previously described the ability of polyunsaturated fat diets to lower plasma described the abilit...

In order to determine whether sphingomyelin (SPH) affects the rate of cholesterol esterification by plasma lecithin-cholesterol acyltransferase (LCAT), we studied the effects of its incorporation in to defined proteoliposome substrates containing phosphatidyl choline (PC), unesterified cholesterol, and apoprotein A-I, on the activity of purified LCAT. Cholesterol esterification was inhibited by...

We had previously shown that the cholesterol esterification activity of lecithin:cholesterol acyltransferase (LCAT) is destroyed by oxidation, but still it retains the ability to hydrolyse water-soluble substrates. This suggested that the inactivation of the enzyme is not due to its catalytic function, but due to a loss of its hydrophobic binding. Since recent studies have shown that a tryptoph...

To separate the interfacial and catalytic reactions of lecithin cholesterol acyltransferase (LCAT), we carried out the first investigation of its reaction with water-soluble substrates. We used a continuous spectrophotometric assay for the hydrolysis of p-nitrophenyl esters of fatty acids to determine the chain length specificity of the enzyme and its modulation by anions and apolipoproteins in...

We have analyzed the effect of charged to neutral amino acid substitutions around the kinks flanking helices 4 and 6 of apoA-I and of the deletion of helix 6 on the in vivo activity of LCAT and the biogenesis of HDL. The LCAT activation capacity of apoA-I in vitro was nearly abolished by the helix 6 point (helix 6P-apoA-I[R160V/H162A]) and deletion {helix 6Delta-apoA-I[Delta(144-165)]} mutants,...

Fish-eye disease is a rare genetic disorder of high density lipoprotein (HDL) metabolism that is characterized biochemically by a partial deficiency of the enzyme lecithin:cholesterol acyltransferase (LCAT). One of the mutations that is causative for fish-eye disease occurs at codon 123 of the LCAT gene. This mutation results in the exchange of a threonine residue for an isoleucine in the LCAT ...

To better understand the role of LCAT in HDL metabolism, we compared HDL subpopulations in subjects with homozygous (n = 11) and heterozygous (n = 11) LCAT deficiency with controls (n = 22). Distribution and concentrations of apolipoprotein A-I (apoA-I)-, apoA-II-, apoA-IV-, apoC-I-, apoC-III-, and apoE-containing HDL subpopulations were assessed. Compared with controls, homozygotes and heteroz...

Familial lecithin: cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder characterized by corneal opacity, hemolytic anemia, proteinuria, and a low serum level of high-density lipoprotein cholesterol (HDL-C). Also, LCAT activity is remarkably decreased or absent. A 57-year-old Japanese man presented with corneal opacity, proteinuria, and a very low serum level of HDL-...

Opacification of the cornea from lipid accumulation is an early and characteristic feature of familial lecithin:cholesterol acyltransferase (LCAT) deficiency. Visual impairment in a female age 48 years led to keratoplasty and the first detailed analysis of cornea in this disorder. Multilaminar figures were present, and total lipid extracts were enriched with phospholipid and cholesterol; choles...

Familial lecithin–cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive disease caused by mutation in the LCAT gene, located on chromosome 16q22 (GenBank accession nos: genomic DNA X04981, cDNA NM_000229). LCAT catalyses the formation of cholesteryl esters via the hydrolysis and transfer of sn-2 fatty acid from phosphatidylcholine to the 3-hydroxyl group of cholesterol. A ...