Retinol-binding protein cellular

Van Aalten, D.M.F., Findlay, J.B.C., Amadei, A., Berendsen,H.J.C. Essential dynamics of the cellular retinol-binding protein. Evidence for ligand-induced conformational changes. Protein Engin. 8 (1995) 1129-1136. 

Retinol (vitamin A) is found in foods of mammalian origin in the form of retinyl ester, or in fruits and vegetables as carotenoids with provitamin A activity, especially P-carotene (provitamin A). In enterocytes, retinol binds to cellular retinol-binding protein type II (CRBPII), which directs the esterification by the enzyme lecithin retinol acyltransferase (LRAT). 

BASF AG CRBPII dba DBN DBU DIBAL-H DMAP DMF DMF-DMA DMPU HMDS HMPA HMPT H-LR LDA LDE LRAT MCPBA MOM NMO NMP PCC PhH = Badische Anilin- Soda Fabrik AG = cellular retinol-binding protein type II r dibenzylideneacetone = 1,5-diazabicyclo[4.3.0]non-5-ene = l,8-diazabicyclo[5.4.0]undec-7-ene = diisobutylaluminium hydride = 4-dimethylaminopyridine = A V-dimethylformamide = A,V-dimethylformamide, dimethylacetal = 1,3 -dimethyl-3,4,5,6-tetrahydro-2( 1H)-pyrimidone = hexamethyldisilazane = hexamethylphosphoramide = hexamethylphosphorous triamide = Hoffmann-La Roche = lithium diisopropylamide = lithium diethylamide = lecithin retinol acyltransferase = m-chloroperbenzoic acid = methoxymethyl = iV-methylmorpholine oxide = l-methyl-2-pyrrolidinone = pyridinium chlorochromate = benzene... 

Retinol is oxidized to retinoic acid. Movement from cytosol to nucleus is guided by cellular retinol-binding proteins and cellular retinoic acidbinding proteins. 

Nakshatri, H., and Chambon, P. (1994). The Directly Repeated RG(G/T)TGA Motifs of the Rat and Mouse Cellular Retinol-Binding Protein II Genes Are Promiscuous Binding Sites for RAR, RXR, HNF-4, and ARP-1 Homo- and Heterodimers./. 

Within the enterocyte, retinol is bound to cellular retinol binding protein (CRBP 11) and is esterified by lecithin retinol acyltransferase (LRAT), which uses phosphatidylcholine as the fatty acid donor, mainly yielding retinyl palmitate, although small amounts of stearate and oleate are also formed. At unphysiologically high levels of retinol, when CRBP 11 is saturated, acyl coenzyme A (CoA) retinol acyltransferase (ARAT) esterifies the free retinol that accumulates in intracellular membranes. Then the retinyl esters enter the lymphatic circulation and then the bloodstream (in chylomicrons), together with dietary lipid and carotenoids (Norum et al., 1986 Olson, 1986 Blomhoff et al., 1991 Green et al., 1993 Harrison and Hussain, 2001). 

The two cellular retinol binding proteins bind aU-trans- and 13-cis-retinol, but not 9-cis- or 11-ds-retinol, or retinoic acid. They also bind retinaldehyde, although there is a distinct retinaldehyde binding protein in the eye ... 

Boerman MH and Napoli JL (1996) Cellular retinol-binding protein-supported retinoic acid synthesis. Relative roles of microsomes and cytosol. Journal of Biological Chemistry 271, 5610-16. 

Thus, it is possible to calculate the off-rates of protein-ligand interactions observed for individual amino acid residues of the protein of a verified reaction mechanism. A nice example that shows various cases was recently published for the Apo-Cellular Retinol Binding Protein (97). 

Mittag T, et al. Retinol modulates site-specific mobility of 118. apo-cellular retinol-binding protein to promote ligand binding. 

Within extra hepatic tissues retinol is bound to cellular retinol binding protein (CRBP). 

Stump, D. G., Lloyd, R. and Chytil, F. (1991). Site irected mutagenesis of rat cellular retinol-binding protein. /. Biol. Chem. 266,4622—4630. 

Cellular retinol-binding protein II CRBPII 1.9 Winter et al. (1993)... 

Fig. 2. Stereodiagrams of LBPs. The ribbon drawings of serum retinol-binding protein (a) and cellular retinol-binding protein (b) are shown in stereo. They are representative of the eLBP and iLBP families, respectively. The retinol molecule found bound to the crystalline protein is shown as a ball-and-stick model.

Wang, B., Merz, K.M. Validation of the binding site structure of the cellular retinol-binding protein (CRBP) by ligand NMR chemical shift perturbations. J. Am. Chem. Soc. 2005,127, 5310-1. 

Preformed vitamin A, most often in the form of retinyi ester, or carotenoids are subject to emulsification and mised micelle formation by the action of bile salts before being transported into the intestinal cell. Here the retinyi esters are moved across the mucosal membrane and hydrolyzed to retinol within the cell to then be reesterified by cellular retinol-binding protein II and packaged into chylomicra, which then enter the mesenteric lymphatic system and pass mto the systemic circulation. A small amount of the ingested retinoid is also converted into retinoic acid in the intestinal cell. The efficiency of absorption of preformed vitamin A is high at between 70% and 90%. ... 

Napoli JL. A gene knockout corroborates the integral function of cellular retinol-binding protein in retmoid metabolism. Nutr Rev 2000 58 230-6. 

Retinaldehyde, when bound to retinol binding protein II (CRBPII), serves as a substrate for retinal reductase resulting in the production of retinol (14), which then binds to cellular retinol binding protein (CRBP) forming holo-CRBP. Holo-CRBP seems to be the preferred substrate for an esterification reaction (Fig. 7.6) mediated by lecithin retinol acyl transferase (LRAT), a microsomal enzyme that uses acyl groups donated from phosphatidylcholine (14).In cells not expressing CRBP, retinol esterification is carried out by a different enzyme, acyl CoArretinol acyl transferase (ARAT). 

Calderone, V., C. Folli, A. Marchesani, R. Bemi and G. Zanotti. Identification and structural analysis of a zebrafish apo- and holo-cellular retinol-binding protein. J. Mol. Biol. 321 527—535, 2002. 

CRBP Cellular retinol-binding protein Gly Glycine... 

Neuville P, Geinoz A, Benzonana G, Redard M, Gabbiani F, Ropraz P, Gabbiani G (1997) Cellular retinol-binding protein-1 is expressed by distinct subsets of rat arterial smooth muscle cells in vitro and in vivo. Am J Pathol 150 509-521... 

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