On the metabolic conversion of human plasma very low density lipoprotein to low density lipoprotein

Abstract

The relationship of 125I-labelled apoproteins of very low density lipoprotein to that of other lipoproteins was studied in humans during steady-state conditions and following heparin injection. Heterogeneous metabolism of very low density lipo-protein apoproteins in normal individuals was apparent during steady-state conditions. Radioactivity transferred to high density lipoprotein immediately in vivo. With time radioactivity also transferred to an intermediate density lipoprotein ( d = 1.006−1.019) and thereafter to low density lipoprotein ( d = 1.019−1.063). Labelled apoLP-glu and apoLP-ala, but not labelled apoprotein of low density lipoprotein (apoLDL), disappeared initially from very low density lipoprotein (10 min after the injection). At later time intervals, the rate of disappearance of labelled apoLDL from very low density lipoprotein ( t 1 2 = 2−4 h ), far exceeded that of labelled apoLP-glu and apoLP-ala ( t 1 2 = 17–18 h ). Heparin affected primarily the distribution of apoprotein radioactivity between very low density lipoprotein and high density lipoprotein and among very low density lipoprotein subfractions. 45 min after heparin injection, a net transfer of more than 50 % of labelled apoLP-glu and apoLP-ala from very low density lipoprotein to high density lipoprotein occurred. Almost no change in content of labelled apoLDL in very low density lipoprotein occurred during this interval. Both very low density lipoprotein mass and radioactivity accumulated in a very low density lipoprotein subtraction of S f 20–60, which contained about twice as much 125I-labelled apoLDL as 125-labelled apoLP-glu and 125I-labelled apoLP-ala. Further decay of labelled apoLDL to lipoproteins of density 1.006–1.019 and then to low density lipoprotein, occurred later, with peak activities 6 and 24 h, respectively, after heparin injection. 6 h after heparin, when plasma triglyceride had increased toward pre-heparin levels, labelled apoLP-glu and apoLP-ala retransferred to very low density lipoprotein (mainly to triglyceride rich, newly synthesized S f > 100 molecules). During the conversion of very low density lipoprotein molecules of S f 100–400 ( mol. wt 20 · 10 6-130 · 10 6) to low density lipoprotein (mol. wt 2.2 · 10 6), all apoLDL moiety of very low density lipoprotein is preserved. In contrast, more than 95% of apoLP-ser, apoLP-glu and apoLP-ala, more than 99% of triglyceride, and more than 85% of the very low density lipoprotein cholesterol and phospholipids are removed. These observations suggest that concomitant with continuous triglyceride hydrolysis, apoLP-glu and apoLP-ala leave the very low density lipoprotein density range resulting in molecules relatively poor in triglyceride and relatively rich in apoLDL. These molecules occupy a notation rate range of S f 12–60 and are trans-formed ultimately to low density lipoprotein, presumably by a different mechanism.