De novo production of low density lipoproteins: fact or fancy

Many investigators, observing an apparent dilution in the plasma specific activity (SA) of apolipoprotein B-100 (apoB) in low density lipoprotein (LDL) as compared with that in very low density lipoprotein (VLDL) after injection of radiolabeled VLDL, have formulated kinetic hypotheses incorporating the concept of de novo production of LDL to explain their data in humans and other mammals. These hypotheses, with rare exception, do not account for the kinetic heterogeneity known to exist in the apoB of human VLDL on the basis of size and in the apoB of rabbit VLDL on the basis of size and presence of apolipoprotein E. When a logical analysis of such kinetic heterogeneity of apoB in plasma VLDL is performed, it becomes clear that the apparent dilution of the SA of apoB in LDL relative to that in VLDL can be explained without the requirement for de novo production of LDL. Although this alternative hypothesis, incorporating the concept of kinetic heterogeneity of apoB in VLDL, does not exclude the process of de novo production of LDL, which so many investigators have invoked to explain their data, it does raise a question as to the existence of such a process since an alternative hypothesis can explain such data just as well. Clearly, more experimental data on the kinetic heterogeneity of human and other mammalian VLDL are needed before a reasonable choice can be made between these two hypotheses.