Abnormal high density lipoproteins of abetalipoproteinemia: relevance to normal HDL metabolism.

We investigated high density lipoprotein (HDL) subfractions in abetalipoproteinemia (ABL) using rate zonal ultracentrifugation. In ABL, HDL2 is the major subfraction, 65% of total mass compared to less than 10% in normal subjects with similar HDL levels. HDL2 and HDL3 in ABL (n = 3) are larger and lighter than in normals (n = 3), with mean diameters of 136 +/- 19 A and 100 +/- 12 A, respectively (as compared to 113 +/- 12 A and 86 +/- 11 A), and contained more apoprotein E. ABL-HDL2 and HDL3 particles contain 2- to 2.5-fold more cholesteryl ester molecules than normals. ABL-HDL can be modified towards normal HDL by allowing VLDL triglycerides to exchange for ABL-HDL cholesteryl esters, followed by addition of lipoprotein lipase and hydrolysis of the triglycerides. In addition, ABL plasma contains a previously undescribed small and spherical (61 +/- 8 A) protein-rich (63% by weight) HDL fraction, which we call ABL-HDL4. Our data suggest that absence of cholesteryl ester transfer to triglyceride-rich lipoprotein in ABL causes accumulation of abnormally large cholesteryl ester-rich particles.