Summary
The lipoproteins from two sibs with familial lecithin-cholesterol-acyltransferase(LCAT)-deficiency were further characterized. Comparatively lipoproteins from patients with secondary LCAT-deficiency were studied. Both groups of patients had particles of unusual size and shape in the α1-(HD-2)-lipoprotein subfraction. The abnormal HDL-2 particles were disk-like in appearance with a major axis of about 180 Å and a minor axis of about 40 Å and tended to aggregate into long coinlike stacks.
The abnormal HDL-2 particles contained the normal protein constituents of HDL Apo A-I, Apo A-II and Apo C but in addition a major polypeptide with a M.W. of 39 000 not seen in significant amounts in normal high-density-lipoproteins. This polypeptide was found identical in size, isoelectric focusing and immunochemically with an arginine-rich normal polypeptide constituent of very-low-density-lipoproteins designated apoprotein E. Presence of this protein marker in the HDL allowed the specific immunological detection of the abnormal HDL-2 (LP-E) in plasma. Further minor biochemical abnormalities were observed in the lipoproteins of the patients with familial LCAT-deficiency. However, the main protein constituents of their HDL, the Apo A, Apo C and Apo E polypeptides, were found to be identical electrophoretically and by analytical isoelectric focusing with their normal counterparts.
The data suggest that the basic genetic defect in the hereditary disease leads to a deficient activity of the LCAT-enzyme and that all abnormalities in the lipoprotein spectrum are secondary.
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Abbreviations
- LCAT:
-
Lecithin-Cholesterol-Acyltransferase (EC 2.3.1.43)
- VLDL:
-
Very-Low-Density-Lipoproteins
- LDL:
-
Low-Density-Lipoproteins
- HDL-2:
-
High-Density-Lipoproteins-2 (d=1.063-1.125 g/ml)
- HDL-3:
-
High-Density-Lipoproteins-3 (d=1.125-1.25 g/ml)
- SDS-PAGE:
-
Polyacrylamide gel electrophoresis in presence of sodium dodecyl sulphate
References
Fielding, C. J., Fielding, P. E.: Purification and substrate specifity of lecithin-cholesterol-acyltransferase from human plasma. FEBS-Letters 15, 355–358 (1971)
Fielding, C. J., Shore, V. G., Fielding, P. E.: A protein cofactor of lecithin-cholesterol-acyltransferase. Biochem. biophys. Res. Commun. 46, 1493–1498 (1972)
Forte, T., Norum, K. R., Glomset, J. A., Nichols, A. V.: Plasma lipoproteins in familial lecithin-cholesterol-acyltransferase deficiency: structure of low and high density lipoproteins as revealed by electron microscopy. J. clin. Invest. 50, 1141 (1971)
Fredrickson, D. S.: The regulation of plasma lipoprotein concentrations as affected in human mutants. Proc. nat. Acad. Sci. (Wash.) 64, 1138–1146 (1969)
Fredrickson, D. S.: Plasma lipoproteins and apolipoproteins. Current topics in biochemistry (eds. C. B. Anfinson and A. N. Schechter), pp. 219–263 (1973)
Gjone, E.: Familial Lcat deficiency. Acta med. scand. 194, 353–356 (1973)
Gjone, E., Norum, K. R.: Familial serum cholesterol ester deficiency. Acta med. scand. 183, 107 (1968)
Glomset, J. A.: The plasma lecithins in cholesterol acyltransferase reaction. J. Lipid. Res. 9, 155–167 (1968)
Glomset, J. A., Janssen, E. T., Kennedy, R., Dobbins, J.: Role of plasma lecithin-cholesterol acyltransferase in the metabolism of high density lipoproteins. J. Lipid. Res. 7, 639 (1966)
Glomset, J. A., Nichols, A. V., Norum, K. R., King, W., Forte, T.: Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency. Further studies of very low and low density lipoprotein abnormalities. J. clin. Invest. 52, 1078–1092 (1973)
Glomset, J. A., Wright, J. L.: Some properties of cholesterol esterifying enzyme in human plasma. Biochim. biophys. Acta (Amst.) 89, 266–276 (1964)
Havel, R. J., Eder, H. E., Bragdon, J. H.: The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. clin. Invest. 34, 1345 (1955)
Havel, R. J., Kane, J. P.: Primary dysbetalipoproteinemia: Predominance of a specific apoprotein species in triglyceride-rich lipoproteins. Proc. nat. Acad. Sci. (Wash.) 70, 2015–2019 (1973)
Kostner, G. M.: Studies of the composition and structure of human serum lipoproteins. Isolation and partial characterisation of apolipoprotein A-III. Biochim. biophys. Acta (Amst.) 336, 383–395 (1974)
Mc Conathy, W. J., Alaupovic, P., Curry, M. D., Magnani, H. N., Torsvik, H., Berg, K., Gjone, E.: Identification of lipoprotein families in familial lecithin-cholesterol-acyltransferase deficiency. Biochim. biophys. Acta (Amst.) 326, 406–418 (1973)
Norum, K. R., Gjone, E.: Familial plasma lecithin-cholesterol acyltransferase deficiency. Scand. J. clin. Lab. Invest. 20, 231 (1967)
Norum, K. R., Glomset, J. A., Nichols, A. V., Forte, T.: Plasma lipoproteins in familial lecithin-cholesterol acyltransferase deficiency: Physical and chemical studies of low and high density lipoproteins. J. clin. Invest. 50, 1131 (1971)
Scheidegger, J. J.: Une micro-méthode de l'immunoélectrophorèse. Int. Arch. Allergy 7 103–110 (1955)
Seidel, D., Alaupovic, P., Furman, R. H.: A lipoprotein characterizing obstructive jaundice. I. Method for quantitative separation and identification of lipoproteins in jaundiced subjects. J. clin. Invest. 48, 1211 (1969)
Seidel, D., Alaupovic, P., Furman, R. H., Mc Conathy, W. J.: A lipoprotein characterizing obstructive jaundice. II. Isolation and partial characterization of the protein moieties of low density lipoproteins. J. clin. Invest. 49, 2396 (1970)
Shore, B., Shore, V., Salel, A., Mason, D., Zelis, R.: An apolipoprotein preferentially enriched in cholesteryl ester-rich very low density lipoproteins. Biochem. biophys. Res. Commun. 58, 1–7 (1974)
Shore, V. G., Shore, B.: Heterogeneity of human plasma very low density lipoproteins. Separation of species differing in protein components. Biochemistry 12, 502–507 (1973)
Torsvik, H.: Further studies on serum α1-lipoprotein in familial lecithin-cholesterol acyltransferase deficiency. Clin. Genet. 1, 310 (1970)
Torsvik, H.: Studies on the protein moiety of serum high density lipoprotein from patients with familial lecithin: cholesterol acyltransferase deficiency. Clin. Genet. 3, 188–200 (1972)
Torsvik, H., Berg, K., Magnani, H. N., Mc Conathy, W. J., Alaupovic, P., Gjone, E.: Identification of the abnormal cholestatic lipoprotein (LP-X) in familial lecithin-cholesterol acyltransferase deficiency. FEBS-Letters 24, 165–168 (1972)
Torsvik, H., Solass, M. H., Gjone, E.: Serum lipoproteins in plasma lecithin cholesterol acyltransferase deficiency, studied by electron microscopy. Clin. Genet. 1, 139 (1970)
Utermann, G.: Disc-electrophoretic patterns of human serum high density lipoproteins. Clin. chim. Acta 36, 521–529 (1972)
Utermann, G.: Manuscript submitted for publication (1975)
Utermann, G., Menzel, H. J., Langer, K. H.: On the polypeptide composition of an abnormal high-density-lipoprotein (LP-E) occurring in LCAT-deficient plasma. FEBS-Letters 45, 29 (1974a)
Utermann, G., Menzel, H. J., Schoenborn, W.: Manuscript submitted for publication (1974b)
Utermann, G., Schoenborn, W., Langer, K. H., Dieker, P.: Lipoproteins in LCAT-deficiency. Humangenetik 16, 295–306 (1972)
Weber, K., Osborn, M.: The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J. biol. Chem. 244, 4406–4412 (1969)
Wrigley, C.: Gel electrofocusing—a technique for analyzing multiple protein samples by isoelectric focusing. Sci. Tools 15, 17 (1968)
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Utermann, G., Menzel, H.J., Langer, K.H. et al. Lipoproteins in lecithin-cholesterol-acyltransferase (LCAT)*-deficiency. Hum Genet 27, 185–197 (1975). https://doi.org/10.1007/BF00278345
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DOI: https://doi.org/10.1007/BF00278345