Serum lipoproteins in plasma lecithin:cholesterol acyltransferase deficiency, studied by electron microscopy

Torsvik, Harald; Solaas, Marit Hornberg; Gjone, E

doi:10.1111/j.1399-0004.1970.tb01629.x

Cited by 32 publications

(5 citation statements)

References 21 publications

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“…Because the liver secretes lecithin-cholesterol acyltransferase (LCAT) (14,15), an inhibitor to this enzyme was added to the perfusate. Under these conditions, the HDL particles were found to resemble closely the discoidal HDL that occur in plasma of patients with genetically determined LCAT deficiency (16,17).…”

Section: Introductionmentioning

confidence: 83%

Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver.

Hamilton¹,

Williams²,

Fielding³

et al. 1976

J. Clin. Invest.

522

136

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A B S T R A C T Rat livers were perfused for 6 h without added plasma proteins using washed erythrocytes and buffer in a recirculating system. An inhibitor to the enzyme lecithin-cholesterol acyltransferase (5,5'-dithionitrobenzoic acid) was added in some experiments to prevent modification of substrate-lipids contained in secreted lipoproteins. The inhibitor did not detectably alter hepatic ultrastructure or gas exchange, but it inhibited the secreted lecithin-cholesterol acyltransferase by more than 85%. Very low density lipoproteins in perfusate were unaltered but the high density lipoproteins obtained from livers perfused with the inhibitor appeared disk-shaped in negative stain by electron microscopy with a mean edge thickness of 46±5 A and a mean diameter of 190±25 A. The high density lipoproteins were composed predominantly of polar lipids and protein with only small amounts of cholesteryl esters and triglycerides. The major apoprotein of these discoidal fractions had the same electrophoretic mobility as the arginine-rich apoprotein, whereas plasma high density lipoproteins contained mainly the A-I apoprotein. In all these respects the discoidal perfusate high density lipoproteins closely resemble those found in human plasma which is deficient in lecithin-cholesterol acyltransferase. Perfusate high density lipoproteins obtained in the absence of the enzyme inhibitor more closely resembled plasma high density lipoproteins in Portions of this work have appeared in an abstract and in a review (1, 2).Dr. Hamilton is the recipient of a Research Career Development Award. Dr. Williams was the recipient of a Postdoctoral Fellowship from the National Heart and Lung Institute. Dr. Fielding was an Established Investigator of the American Heart Association.Received for publication 30 January 1976 and in revised form 12 April 1976. chemical composition (content of cholesteryl esters and apoproteins) and in electron microscopic appearance. Purified lecithin-cholesterol acyltransferase synthesized cholesteryl esters at a substantially faster rate from substrate lipids of perfusate high density lipoproteins than those from plasma. The discoidal high density lipoproteins were the best substrate for this reaction. Thin sections of plasma high density lipoproteins indicated a spherical particle whereas discoidal high density lipoproteins stained with the characteristic trilaminar image of membranes. These observations suggest that the liver secretes disk-shaped lipid bilayer particles which represent both the nascent form of high density lipoproteins and preferred substrate for lecithin-cholesterol acyltransferase. INTRODUCTIONThe plasma lipoproteins are usually separated into four major physically defined groups although it is recognized that heterogeneity exists within each. This heterogeneity is further complicated by movements of both lipids and apoproteins between particles of the different groups. One approach to obtain a clearer understanding of the physiological significance of the different plasma lipoproteins h...

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Section: Introductionmentioning

confidence: 83%

Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver.

Hamilton¹,

Williams²,

Fielding³

et al. 1976

J. Clin. Invest.

522

136

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“…Electron micrographs of lipoproteins from normal subjects and the patients have been described previously (Torsvik et al 1970). Particles in the LDL and the HDL fractions from the mother of the patients were of normal appearance (Figs.…”

Section: Electron Microxopical Studiesmentioning

confidence: 89%

“…Stepwise ultracentrifugation was performed as described previously (Torsvik 1969), giving lipoproteins of the following densities: ( 1.006 g/ml, 1.006-1.019 g/ml, 1.019 -1.063 g/ml, 1.063-1.195 g/ml, and ) 1.195 g/ml. The high density lipoprotein (HDL), 1.063-1.195 g/ml, was further purified by chromatography on hydroxylapatite (Torsvik et al 1970).…”

Section: Preparation Of Lipoprotein Fractionsmentioning

confidence: 99%

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Further studies on serum α₁‐lipoprotein in familial lecithin:cholesterol acyltransferase deficiency

Torsvik

1970

Clinical Genetics

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Serum high density lipoprotein (HDL) from two patients with LCAT deficiency has been compared with HDL from normal subjects and HDL from a presumed heterozygous carrier. By two different immunological methods the concentration of ‐lipoprotein in serum of the patients was found to he about 25–30 % of the normal concentration. Patient HDL is cornpoked of two fractions, as shown previously. The first fraction contains particles of high molecular weight with an electrophoretic mobility slightly slower than that of normal HDL. The lipid content is 70%, and the concentrations of unesterified cholesterol and phospholipids are about 10–15 and 3–4 times that of normal HDL, respectively. The second fraction consists of particles of relatively low molecular weight with electrophoretic mobility faster than albumin. This fraction exhibits closc to normal concentrations of unesterified cholesterol and phospholipids. Esterified cholesterol or lysolccithin could he demonstrated in none of the fractions. HDL from the prewmed hetcrozygous carrier was normal as judged from immunoelectro‐phoresis, gel filtration, electron microscopy. and lipid analyses.

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“…HDL was prepared by flotation in the ultracentrifuge at a density of 1.063-1.21 g/ml at 105,000 g for 48 hr and further purified by chromatography on hydroxylapatite as described by Hjerten (1959) and Torsvik et al (1970). The isolated HDL was delipidated by extraction with ethanol-diethylether, treated with 8 M urea, and submitted to gel filtration on Sephadex G-200, details of which have been described (Scanu et al 1969;Berrresen 1976b).…”

Section: Preparation Of H D L and Hdl Polypeptidesmentioning

confidence: 99%

PURIFICATION AND PARTIAL CHARACTERIZATION OF THE apoA‐I OF RABBIT HIGH DENSITY LIPOPROTEIN

Børresen

Kindt

1978

Int J Immunogenetics

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SUMMARY Purfication of apoA‐I from rabbit high density lipoproteins (HDL) gave one single band in sodium dodecylsulphate‐polyacrylamide disc electrophoresis and reacted only with antiserum to apoA‐I. The molecular weight was about 25000. The amino acid composition of rabbit apoA‐I gave a difference index of 7.4 compared to human apoA‐I and of 6.5 compared to dog apoA‐I. Of the three carboxy terminal amino acid residues the rabbit protein has one in common with the dog. The amino acid sequence of twenty‐nine amino terminal residues showed 62% homology with the human protein; a minimum of thirteen base changes were required in the DNA sequences that encoded these two proteins. When the same sequence was compared with dog apoA‐I, it was found that ten base changes would be sufficient to account for the differences between the proteins.

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Serum lipoproteins in plasma lecithin:cholesterol acyltransferase deficiency, studied by electron microscopy

Cited by 32 publications

References 21 publications

Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver.

Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver.

Further studies on serum α₁‐lipoprotein in familial lecithin:cholesterol acyltransferase deficiency

PURIFICATION AND PARTIAL CHARACTERIZATION OF THE apoA‐I OF RABBIT HIGH DENSITY LIPOPROTEIN

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Serum lipoproteins in plasma lecithin:cholesterol acyltransferase deficiency, studied by electron microscopy

Cited by 32 publications

References 21 publications

Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver.

Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver.

Further studies on serum α1‐lipoprotein in familial lecithin:cholesterol acyltransferase deficiency

PURIFICATION AND PARTIAL CHARACTERIZATION OF THE apoA‐I OF RABBIT HIGH DENSITY LIPOPROTEIN

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Further studies on serum α₁‐lipoprotein in familial lecithin:cholesterol acyltransferase deficiency