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
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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