Holo-retinol-binding protein

BJ Burri, MA Kutnink, TR Neidlinger. Assay of human transthyretin-bound holo-retinol-binding protein with reversed-phase high-performance liquid chromatography. J Chromatogr 567 369-380, 1991. 

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

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. 

The first lipocalin whose 3-D structure was solved and refined at high resolution was the human plasma retinol-binding protein (RBP) [22, 23]. RBP acts as a natural transporter of vitamin A (retinol) in the blood of vertebrates. Upon complexation in a hydrophobic cavity with complementary shape, the poorly soluble terpenoid alcohol becomes packaged by the protein and protected from oxidation or double-bond isomerization. RBP is synthesized in the liver and directly loaded with fhe hgand in fhe hepatocyte, where retinol is stored. Furthermore, the holo-RBP forms a structurally defined ternary complex with transthyretin [24], also known as prealbumin. After delivery of the retinol ligand to a target tissue, fhe complex decomposes and fhe monomeric apo-RBP becomes filtered out by fhe kidney and degraded. 

Jaconi, S., Saurat, J. H., and Siegenthaler, G. 1996. Analysis of normal and truncated holo-and apo-retinol binding protein (RBP) in human serum Altered ratios in chronic renal failure. EurJ Encrinol 134 576-582. 

Winter, N S, Bratt, J. M, and Banaszak, L J. (1993) Crystal-structures of holo and apo-cellular retinol-binding protein-II J Mol Biol 230, 1247-1259... 

The peculiar spectral properties of CRBP-bound retinol and RME are indicative of specific ligand-protein interactions (see Fig. 2) Instead, other holo-retinoid-binding proteins exhibit less characteristic spectra. For example the absorption spectrum of the complex of retinol with plasma retinol-binding protein (RBP) is characterized by a single, well-shaped peak centered at approx 328 nm On the other hand, the absorption spectra of some CRBP-bound retinoids, like CRBP-bound a l-trans retinal (12,13), do not resemble those of CRBP-bound retinol and RME. 

Vitamin A is transported m the plasma as retinol bound to a carrier protein, called retinol-binding protein (RBP), which itself forms a complex with the thyroxine-binding protein, known as transthyretin (TTR). This complex exists in equilibrium with free holo-RBP, which can then interact with a specific cell-surface receptor, thereby inducing the release of its retinol to the target cell. Thus, RBP possesses at least three molecular-recognition properties it binds retinol and it interacts with both TTR and the cell-surface receptor (for reviews, see refs. I and 2). 

Posch KC, Boerman MHEM, Bums RD, Napoli JL (1991) Holo-cellular retinol binding protein as a substrate for microsomal retinal synthesis. Biochemistry 30 6224-6230... 

Penzes P, Napoli JL (1999) Holo-cellular retinol-binding protein distinction of ligand-binding affinity from efficiency as substrate in retinal biosynthesis. Biochemistry 38 2088-2093... 

Retinol-binding protein, bovine human, holo and apo... 

Liver Storage and Release of Retinol Tissues can take up retinyl esters from chylomicrons, but most is left in the chylomicron remnants that are taken up into the liver by endocytosis. The retinyl esters are hydrolyzed at the hepatocyte cell membrane, and free retinol is transferred to the rough endoplasmic reticulum, where it binds to apo-RBP. Holo-RBP then migrates through the smooth endoplasmic reticulum to the Golgi and is secreted as a 1 1 complex with the thyroid hormone binding protein, transthyretin (Section 2.2.3). 

Plasma retinol is transported by a specific 21-kDa transport protein, retinal binding protein (RBP). Most RBP is produced in the liver, but some extra-hepatic organs also synthesize it. Each molecule of RBP binds one molecule of all-tra s-retinol nonco-valently. In plasma, the retinol-RBP complex (holo-RBP) forms a larger complex with a cotransport... 

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