Identification of lipoprotein families in familial lecithin: Cholesterol acyltransferase deficiency

Abstract

1. 1. The lipoprotein families in plasma very low density lipoproteins ( d < 1.006 g/ml), low/density lipoproteins 1 ( d = 1.006−1.019 g/ml), low density Iipoproteins 2 ( d = 1.019−1.063 g/ml), high density lipoproteins ( d = 1.063−1.21 g/ml), and very high density lipoproteins (“1.21 infranate”, d > 1.21 g/ml) isolated from three patients with familial lecithin:cholesterol acyltransferase deficiency were studied by immunodiffusion, immunoelectrophoresis, and polyacrylamide gel electrophoresis. 2. 2. The plasma lipoprotein system in patients with lecithin:cholesterol acyltransferase deficiency was found to contain all the apolipoproteins and their constitutive polypeptides identified previously in plasma lipoproteins of normal subjects. In addition to apolipoprotein B and A-I, A-II, C-I, C-II, and C-III polypeptides, the lipoprotein system in lecithin:cholesterol acyltransferase-deficient plasma also contained an immunochemically distinct apolipoprotein which was previously designated as “thin-line” polypeptide. 3. 3. The qualitative distribution of lipoprotein families in major density classes of the patients' plasma closely resembled that of normal, fasting plasma. The lipoprotein B and C families were present as associations in very low density lipoproteins and low density lipoproteins 1, and as free, unassociated fonns in low density lipoproteins 2 and high density lipoproteins. The lipoprotein A family occurred as free forms in high and very high density lipoproteins. 4. 4. Some major qualitative and quantitative differences were found between the lipoprotein systems of normal and lecithin:cholesterol acyltransferase-deficient subjects. The most significant qualitative difference was the occurrence in the patients' plasma of lipoprotein X, the abnormal low density lipoprotein species characteristic of obstructive jaundice. Its concentration in the low density lipoproteins of three patients varied between 49 and 152 mg/1oo ml. The major quantitative difference was the reduced concentration of apolipoproteins A and B in lecithin:cholesterol acyltransferase-deficient plasma. In addition to the previously demonstrated decrease in the concentration of apolipoprotein A (Torsvik H. (1969) Scand. J. Clin. Lab. Invest. 24, 187–196), the concentration of plasma apolipoprotein B was found to be onethird to one-half of that in normal subjects. The low concentration of plasma apolipoprotein B was due to the reduction of apolipoprotein B in low density lipoproteins. The already established differences in the lipid compositions of the major lipoprotein A family from enzyme-deficient and normal subjects were not accompanied by a corresponding change in the polypeptide composition of apolipoprotein A. In both cases, the apolipoprotein A consisted of A-I and A-II polypeptides. The abnormalities of the plasma lipoprotein system in familial lecithin:cholesterol acyltransferase deficiency seem to result from, rather than cause, the virtual absence of enzyme activity.