The methodology of compartmental modeling as applied to the investigation of lipoprotein metabolism

Abstract

The statements to this point only give a cursory review of the beginning (20 years) of the kinetic approach to the classification of lipoproteins and subsystems which are involved in their synthesis and metabolism. At the present time the following partial list of theoretical findings expressed through model building can be made for the lipid and lipoprotein field: A cascade process of delipidation for VLDL exists and the rate of this process is decreased in subjects with hyperlipoproteinemia. ApoC recycles between VLDL and HDL in response to the dynamics of the delipidation cascade. New synthesis of apoB first appears with newly synthesized VLDL. VLDL apoB synthesis decreased in hyperlipidemic states examined. Multiple synthesis pathways exist for the triglyceride moiety of VLDL as determined by the transit time of a precursor through the conversion pathway. Thus the isotopic precursor methods now yield the same results as the more invasive techniques. Kinetic heterogeneity of VLDL, IDL, LDL, and HDL has been established. Kinetic heterogeneity for apoA-I, apoA-II, apoB, apoC-2 and apoC-3 have been established. The presence of direct pathways for IDL and LDL synthesis have been established. Irreversible loss of apoC from HDL has been predicted using models. Synthesis of apoC has been found to be invariant in hyperlipoproteinemic states studied. Hepatic cholesterol compartments associated with the formation of bile acids and biliary cholesterol derive a majority of their cholesterol from newly synthesized and lipoprotein-free cholesterol. More than 85% of the free cholesterol in the beta-lipoproteins cycles directly through the HDL. Free cholesterol recycles between HDL and tissue pools and between HDL and beta-lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)