The nature of pre beta (very low density) lipoproteins.

The plasma lipoproteins and "particles"' fall into four major groups. As defined by paper electrophoresis (3) these are the beta, alpha, and pre-beta lipoproteins, and chylomicrons. The latter two are rich in glyceride and very low in density (< 1.006, Sf > 20). It is now common to reserve the term chylomicrons for the relatively large particles that arise in the gut from exogenous or ingested fat and that usually have Sf values > 105 (2). The endogenous glycerides are found primarily in the pre-beta lipoproteins and particles; in the analytical ultracentrifuge these form concentration maximums distinct from those of the beta-migrating low density lipoproteins of Sf 0 to 20, and when isolated as a group in the preparative ultracentrifuge they are often referred to as very low density lipoproteins (VLDL) (3, 4). The VLDL have sometimes been considered to represent beta lipoproteins in association with variable amounts of glycerides added by the liver, a viewpoint encouraged by the prevailing immuno-chemical data. The latter are not all in agreement (5, 6), but most of the evidence, including that presented in the most recent review of the subject (6), suggests that VLDL are antigenically homogenous and identical to the beta lipoproteins. There exist certain other pieces of information, however, which are not in accord with this assumption. Some of the properties of VLDL or pre-beta lipoproteins suggest that polypeptides in addition * 1 The term "particle" is used in the context suggested by Dole and Hamlin (2) to signify any lipoprotein complex of sufficient size to be seen in a dark field microscope. to those in the beta lipoproteins are present. A greater negative charge is needed to explain the pre-beta mobility on paper (3) or alpha, mobility on starch (7) of VLDL. Also, if triglyceride were simply added to beta lipoproteins, the ratio of cholesterol to phospholipid would be expected to remain unchanged; instead it falls sharply as the flotation rate of lipoproteins exceeds Sf 20 (8). Furthermore, in contrast to beta lipoproteins (5, 9-11), glutamic acid has not been the sole amino-terminal acid in proteins isolated from VLDL (10-12). Included have been significant amounts of aspartic acid, known to be amino-terminal in the polypeptide characteristic of alpha lipo-protein (5, 9-11), as well as serine and threonine. Pertinent to this last finding are innumerable observations that the plasma concentrations of alpha lipoproteins bear a reciprocal relationship to the concentrations of …