RBP

The first example is the plasma-borne retinol-binding protein, RBP, which is a single polypeptide chain of 182 amino acid residues. This protein is responsible for transporting the lipid alcohol vitamin A (retinol) from its storage site in the liver to the various vitamin-A-dependent tissues. It is a disposable package in the sense that each RBP molecule transports only a single retinol molecule and is then degraded. 

RBP is synthesized in the hepatocytes, where it picks up one molecule of retinol in the endoplasmic reticulum. Both its synthesis and its secretion from the hepatocytes to the plasma are regulated by retinol. In plasma, the... 

Figure S.3 Schematic diagram of the structure of human plasma retinol-binding protein (RBP), which is an up-and-down P barrel. The eight antiparallel P strands twist and curl such that the structure can also be regarded as two p sheets (green and blue) packed against each other. Some of the twisted p strands (red) participate in both P sheets. A retinol molecule, vitamin A (yellow), is bound inside the barrel, between the two P sheets, such that its only hydrophilic part (an OH tail) is at the surface of the molecule. The topological diagram of this stmcture is the same as that in Figure 5.2. (Courtesy of Alwyn Jones, Uppsala, Sweden.)...

Figure S.4 The binding site for retinol inside the RBP barrel is lined with hydrophobic residues. They provide a hydrophobic surrounding for the hydrophobic part of the retinol molecule.

There is a second family of small lipid-binding proteins, the P2 family, which include among others cellular retinol- and fatty acid-binding proteins as well as a protein, P2, from myelin in the peripheral nervous system. However, members of this second family have ten antiparallel p strands in their barrels compared with the eight strands found in the barrels of the RBP superfamily. Members of the P2 family show no amino acid sequence homology to members of the RBP superfamily. Nevertheless, their three-dimensional structures have similar architecture and topology, being up-and-down P barrels. 

A second example of up-and-down p sheets is the protein neuraminidase from influenza virus. Here the packing of the sheets is different from that in RBP. They do not form a simple barrel but instead six small sheets, each with four P strands, which are arranged like the blades of a six-bladed propeller. Loop regions between the p strands form the active site in the middle of one side of the propeller. Other similar structures are known with different numbers of the same motif arranged like propellers with different numbers of blades such as the G-proteins discussed in Chapter 13. 

Gram-positive or other -negative bacteria, rbp genes could have been replaced by csp genes in cyanobacteria. 

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

The six-coordinate [RTp]SnR Cl3 n derivatives are typically characterized by 119Sn NMR signals in the range -195 to - 670 ppm (relative to Me4Sn) (115,118,120,121), while five-coordinate [RBp]SnR Cl3 n complexes exhibit shifts to lower field in the range -103 to -182 ppm (115). For [Tp lSnR derivatives, the 119Sn chemical shift was also determined to be a linear function of n (120). 

The other major class of extracellular LBPs of mammals is the lipocalins (Flower, 1996). These are approximately 20 kDa, P-sheet-rich proteins, performing functions such as the transport of retinol in plasma or milk, the capture of odorants in olfaction, invertebrate coloration, dispersal of pheromones, and solubilizing the lipids in tears (Flower, 1996). The retinol-binding protein (RBP) of human plasma is found in association with a larger protein, transthyretin, the complex being larger than the kidney threshold and thus not excreted, although the RBP itself may dissociate from the complex to interact with cell surface receptors in the delivery of retinol (Papiz et al., 1986 Sundaram et al., 1998). 

Repeatedly it was shown that the semm retinol level and RBP level in prematures are significantly lower than that of neonates (Shah and Rajalekshmi, 1984). In the liver of prematures, significantly lower retinol levels can be foimd in comparison to neonates (Shensi et ah, 1985). Plasma values lower than 20 gg/dl are not rare in this case and they should be taken as an indicator of a relative vitamin A deficit. But a moderate vitamin A deficiency is not only a problem of countries with poor or inadequate food sources. 

These results show that retinyl esters in respiratory epithelium and in alveolar cells form a pool of vitamin A, which can be used physiologically by the tissue. The formation of retinol and at least RA from retinyl esters is strictly controlled. So far an unphysiological formation of RA and a subsequent toxicity seems not possible. Retinyl esters, however, are biochemically inert with respect to gene expression or vitamin A activity as long as they are not hydrolyzed. Consequently, the inhalative application, especially in cases of insufficient lung development, could represent a true alternative. The oral contribution is hardly successful because of the poor RBP s)mthesis of the liver and the lack of availability of a parenteral solution is currently not available. 

In a placebo-controlled randomized supplementation trial (approved by the ethic commission of Ethiopia) in the rural area (AZOZO) district of Gondar Ethiopia from 220 households, 161 children (2-5 years of age) were selected at random for the study at a first visit to the local clinic, nutritional assessment, and stool examination (parasites or ova) were performed (Biesalski et ah, 1999). 141 children with parasites were treated with mebendazole. Heparin blood was obtained for assessment of vitamin A, RBP, and TTR (transthyretine) concentrations. 

Twenty-five children selected at random received aerosol treatment with RP 6000 vitamin A units per 2 weeks over 3 months being provided. Twenty-five further children served as controls receiving a placebo also aerosol delivered. The aerosol was administered through the mouth during breath inhalation with an adapter. No adverse effects or reactions were observed during inhalation and the children complied well with the treatment. Trained field workers performed the inhalation trials and blood sampling. In the study and control group. Heparin blood samples were collected before and at completion of the study for measurements of vitamin A, RBP, and TTR concentrations. 

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