The assembly and secretion of apoB-100-containing lipoproteins

Role of insulin in hepatic fatty acid partitioning: emerging concepts

“…Newly synthesized polypeptide that remains associated with the ER membrane, rather than being translocated into the lumen, is degraded. In addition, a proportion of apoB-containing nascent particles within the lumen are also targeted for degradation [108]. This possibility is supported by the results of experiments on HepG2 cells, in which a 70 kDa product of apoB degradation was found associated partly with the lumenal contents of the ER [170].…”

“…From experiments conducted on cultured hepatocytes obtained from fed or starved rats, Davis et al [171] concluded that the availability of apoB %) , which is the major B apoprotein in rat liver, determines the rate of TAG secretion. The question has also been addressed by Boren et al [108], working on HepG2 cells. They concluded that it is the availability of TAG that determines the proportion of apoB that is committed to secretion and spared degradation within the lumen of the ER ; increased availability of TAG did not determine the fraction of apoB translocated into the ER lumen, but increased the number of mature VLDL particles formed [108].…”

“…The question has also been addressed by Boren et al [108], working on HepG2 cells. They concluded that it is the availability of TAG that determines the proportion of apoB that is committed to secretion and spared degradation within the lumen of the ER ; increased availability of TAG did not determine the fraction of apoB translocated into the ER lumen, but increased the number of mature VLDL particles formed [108]. More recent work from this group [116] has further supported this conclusion, and the two-step hypothesis in general.…”

“…This translocation is accompanied by the acquisition of a TAG core, and thus the formation of a nascent lipoprotein particle. A model that has been suggested to account for this postulates that, during insertion of apoB across the membrane and into the lumen of the rER, the TAG passes through the disrupted membrane and is accepted into a hydrophobic pocket formed by the apoB molecule itself [102,107,108] (see inset in Figure 2). Assembly of TAG-rich apoB lipoproteins has an obligatory requirement for a lumenal microsomal triacylglycerol transfer protein [109].…”

“…Several accounts of the detailed arguments in favour of the different models have appeared (see, e.g., [108,[111][112][113]). It will suffice to summarize the three models that have emerged as being the most plausible, each apparently based on good experimental evidence.…”