Retinol transport

During, A, and Harrison, EH, 2007. Mechanisms of provitamin A (carotenoid) and vitamin A (retinol) transport into and out of intestinal Caco-2 cells. J Lipid Res 48, 2283-2294. 

The first study was conducted to determine whether carotenoids and cholesterol share common pathways (transporters) for their intestinal absorption (During et al., 2005). Differentiated Caco-2 cells on membranes were incubated (16 h) with a carotenoid (1 pmol/L) with or without ezetimibe (EZ Zetia, an inhibitor of cholesterol transport), and with or without antibodies against the receptors, cluster determinant 36 (CD36) and scavenger receptor class B, type I (SR-BI). Carotenoid transport in Caco-2 cells (cellular uptake + secretion) was decreased by EZ (lOmg/L) as follows P-C and a-C (50% inhibition) P-cryptoxanthin and LYC (20%) LUT ZEA (1 1) (7%). EZ reduced cholesterol transport by 31%, but not retinol transport. P-Carotene transport was also inhibited by anti-SR-BI, but not by anti-CD36. The inhibitory effects of EZ and anti-SR-BI on P-C transport... 

They are also important in intracellular trafficking and transport of retinoids. CRBP(II) interacts direcdy with the enterocyte membrane retinol transporter, and CRBP(I) with the cell surface RBP receptor, thus permitting direct uptake and accumulation of retinol from the intestinal lumen and circulation respectively. CRBP(l) is present in large amounts in cells that synthesize and... 

To mobilize liver stores, our model predicts that retinyl esters in PC or SC are hydrolyzed and the resulting retinol is transferred to the slower turning-over retinol pool (compartment 5 in SC and 3 in PC), presumably bound to CRBP. It is then transferred to an exocytosis compartment. Our kinetic data indicate that this retinol does not need to go back to PC before secretion into plasma. Maybe apoRBP can interact with RBP receptors and equilibrate retinol between intraceUular CRBP and plasma RBP. If so, this is an excellent example of homeostatic control since cellular retinol pools are in equilibrium with plasma retinol. If an exchange of retinol between apoC P and apoRBP is shovm to be mediated by a specific membrane protein, the protein should perhaps be named a retinol transporter, rather than an RBP receptor (Blomhoff et aL, 1991). 

The retinol transport system provides an interesting model for the study of protein-protein and protein-retinoid interactions and of the characteristics and metabolic regulation of a specific binding and transport system. The aim of this chapter is to summarize the information available about this transport system, including information about the structure and chemistry, biochemistry, and metabolism of RBP, and about related clinical phenomena. Brief comments are also... 

The effects of protein-energy malnutrition (PEM), and its treatment, on the plasma retinol transport system have been investigated in a large number of studies during the past decade. Patients with PEM have decreased plasma concentrations of RBP, TTR, and vitamin A. Two major factors can contribute to these low plasma concentrations. First, patients with PEM manifest a defective hepatic production of RBP because of a lack of substrate (calories, amino acids from dietary protein) needed for RBP synthesis. Thus, PEM per se is associated with impaired production of RBP and TTR and defective vitamin A mobilization from the liver. Second, however, PEM is often accompanied by inadequate... 

Plasma vitamin A and RBP levels have been investigated in patients with cystic fibrosis of the pancreas (Smith et al., 1972 Knopfle et al., 1975 Palin et al, 1979). Plasma vitamin A and RBP levels have been found to be lower than normal in patients with cystic fibrosis, despite the administration of oral vitamin A supplements adequate to maintain normal hepatic stores. In one study (Smith et al., 1972), the plasma vitamin A transport system was studied in 43 patients with cystic fibrosis receiving oral supplements of vitamin A and in 95 normal control subjects of a similar age range. The mean plasma concentrations of vitamin A and RBP were significantly lower in the patients than in the controls. Moreover, in cystic fibrosis patients each component of the transport system failed to show the normal age-related rise. It is not known whether these abnormalities of the retinol transport system are primary or secondary features of cystic fibrosis the abnormalities may, however, play a role in the pathophysiology of the disease. 

IRBP has the capacity to bind retinol formed when eyes are exposed to light. Therefore, provided it can diffuse freely through the matrix (which contains proteoglycans), it is a possible candidate for a retinol transport protein between the retina and the RPE (Liou et al.. 1982c). If so, there may be receptors for this protein on the plasma membranes of cells that line the space between the retina and RPE. The glycoprotein may also be internalized together with its ligand thus Orzalesi et al. (1982) have described coated pits and vesicles in RPE that may be associated with this activity. 

Gerlach TH, Zile MH (1991) Metabolism and secretion of retinol transport complex in acute renal failure. 

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