Mechanisms of Formation of Low Density Lipoproteins: Metabolic Pathways and Their Regulation

The pathways of formation of low density lipoproteins in humans and experimental animals were poorly understood prior to the present decade. The concept that LDL particles are primarily formed from VLDL could be developed only after a better understanding of the nature of the protein moiety of lipoproteins (the apolipoproteins) was achieved.1–21* Nevertheless, it had been suggested by several earlier investigators that some constituents of LDL are derived from VLDL. In a classical study published in 1958, Gitlin et al. 22 demonstrated a precursorproduct relationship between the protein moiety of VLDL and LDL, and similar relationships were shown in the 1960s with the triglyceride moiety of these lipoproteins.23,24 In the present chapter an attempt will be made to review recent data concerned with the metabolic relationship of VLDL and LDL. The similarities in the composition and structure of VLDL and LDL will be discussed in the first section. The following sections will describe the pathways of formation of “intermediate lipoproteins” and LDL particles, and the last section will present an integrated scheme of VLDL and LDL metabolic relationships and possible mechanisms regulating plasma LDL levels.