Formation of Apo-RBP with Retinol

As discussed above, in retinol deficiency newly synthesized apo-RBP accumulates in the hepatic endoplasmic reticulum (microsomal fraction), whereas the secretion of serum albumin, TTR, and other plasma proteins appears to continue at a normal rate. The mechanisms responsible for the selective retention of RBP in the endoplasmic reticulum and for the specific stimulation of RBP secretion when retinol is made available, are not known. 

In addition to retinol deficiency, a number of factors may affect the extent to which retinol is available, at the appropriate anatomic locus within the liver cell, for complex formation with apo-RBP. In view of the critical role played by retinol in influencing the rate of RBP secretion, these factors can be considered as potentially significant with regard to the regulation of RBP secretion. Thus, these factors warrant exploration and delineation. 

Retinyl ester stored in the liver must be hydrolyzed before the retinol can be mobilized from the liver as the retinol-RBP complex. Information is needed as to whether or not the processes of retinyl ester hydrolysis and of RBP production and secretion might, under some circumstances, be coordinated in some way. The question to be asked is whether or not the hydrolysis of retinyl esters might at times serve as one of the regulatory steps in the overall process of retinol mobilization from the liver. Information available about the enzymatic hydrolysis of retinyl esters in liver is reviewed in Chapter 7. 

Other factors that may affect the availability of retinol for complex formation with apo-RBP are (1) the manner in which retinol is transported within the cell from the site(s) of retinyl ester hydrolysis to a molecule of apo-RBP and (2) the manner in which the retinol molecule is presented to the membrane-bound molecule of apo-RBP. In this regard, the possible roles of cellular retinol-binding protein (CRBP) and of the so-called cytosol retinyl ester lipoprotein complex in delivering retinol to apo-RBP need exploration (Chen et al., 1981 Sklan et al., 1982). More information is also needed about the movement of retinol between hepatocytes and fat-storing cells (lipocytes) under normal and abnormal conditions. These various topics are also reviewed in Chapter 7. 

Studies with Isoiated Liver Ceiis in Cuiture 

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A number of biochemical processes are involved in the phenomena of RBP synthesis and secretion. These include (1) biosynthesis of RBP (2) processing of the newly synthesized RBP molecule (3) translocation (directed movement) of the newly synthesized RBP molecule in the cell (4) complex formation of apo-RBP with retinol and (5) secretion of the retinol-RBP complex (holo-RBP) from the cell. The information currently available about these processes is reviewed below. 

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