Altered metabolism of low density lipoprotein in humans after prolonged incubation in plasma

1. Lecithin: cholesterol acyltransferase (LCAT) in combination with exchange and transfer proteins is known to alter the composition of all plasma lipoprotein fractions. 2. Human plasma from healthy donors was incubated for 24 h at 37°C in the absence and at 4°C and at 37°C in the presence of the LCAT inhibitors sodium iodoacetate (5 mmol/l), and the low density lipoprotein fractions (LDL) were isolated. 3. LDL isolated from LCAT-active plasma (LDL-a) exhibited pronounced alterations in their surface material: the relative content of phospholipids and of free cholesterol was reduced and the content of tetramethylurea-soluble apolipoproteins was increased. LDL isolated from plasma incubated at 37°C with or without sodium iodoacetate showed significantly increased triglyceride concentrations. 4. The LDL fractions from LCAT-active and LCAT-inactive (LDL-i) incubates were iodinated with 125I and 131I respectively, and their metabolic behaviour was studied in humans. 5. LDL-a was cleared from circulation at a slower rate as compared with LDL-i (t1/2 = 3.17 ± 0.47 vs 2.88 ± 0.45 days). The apparent fractional catabolic rate of LDL-a, calculated according to a two-pool model, was reduced by 22.2 ± 3.1%. Comparing LDL-a with LDL isolated from LCAT-inactive plasma which had been incubated at 37°C, the changes in the metabolic variables were less pronounced. 6. It is concluded that physiological alterations of the chemical compositions, caused by LCAT and exchange/transfer proteins, influence the metabolism of LDL.