Disease relevance of Vitamin A

• Characterization of a dehydrogenase activity responsible for oxidation of 11-cis-retinol in the retinal pigment epithelium of mice with a disrupted RDH5 gene. A model for the human hereditary disease fundus albipunctatus [1].

High impact information on Vitamin A

• CRALBP is not expressed in photoreceptors but is abundant in the retinal pigment epithelium (RPE) and Müller cells of the neuroretina, where it carries 11-cis-retinol and 11-cis-retinaldehyde [2].
• Although the natural substrate for isomerization is not known, all-trans-retinyl palmitate is processed in vitro to 11-cis-retinol by pigment epithelial membranes [3].
• These findings support a role for CRALBP as an acceptor of 11-cis-retinol in the isomerization reaction of the visual cycle [4].
• These findings establish a catalytic role, in conjunction with lecithin:retinol acyltransferase, for RPE65 in synthesis of 11-cis-retinol, and its identity as the isomerohydrolase [5].
• A 600 X g supernatant from a frog retina/pigment epithelium homogenate transforms added all-trans-[3H]retinol, in a time-dependent fashion, to a mixture of 11-cis-retinol, 11-cis-retinal, and 11-cis-retinyl palmitate [6].

Biological context of Vitamin A

• Delayed dark adaptation in 11-cis-retinol dehydrogenase-deficient mice: a role of RDH11 in visual processes in vivo [7].
• Approximately 7% of the binding sites were saturated with endogenous ligand (11-cis-retinol, 88%; all-trans-retinol, 12%) following isolation from partially bleached cattle eyes.(ABSTRACT TRUNCATED AT 400 WORDS)[8]
• In Muller cells, esterification of 11-cis-retinol was four times greater than esterification of all-trans-retinol [9].
• Second, this ester is transformed into 11-cis-retinol by an isomerohydrolase in a process that couples the negative free energy of hydrolysis of the acyl ester to the formation of the strained 11-cis-retinol [10].
• Substrate specificities and mechanism in the enzymatic processing of vitamin A into 11-cis-retinol [11].

Anatomical context of Vitamin A

• Furthermore, photoreceptor RDH12 could be involved in the production of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pigments [12].
• Preferential release of 11-cis-retinol from retinal pigment epithelial cells in the presence of cellular retinaldehyde-binding protein [13].
• Assays of isomerase activity reveal that Rpe65 strongly stimulates the enzymatic conversion of all-trans-retinyl palmitate to 11-cis-retinol in microsomes from bovine RPE cells [14].
• Primary cultures of chicken Muller cells and cell membrane were incubated with all-trans- or 11-cis-retinol to study retinyl ester synthesis [9].
• We conclude that 1) VA, RA, and BUT have differential effects on rabbit fibroblast proliferation; 2) retinoid effects on fibroblast growth vary with the tissue of origin; and 3) VA, RA, and BUT modestly inhibit fibroblast contraction of extracellular matrices [15].

Associations of Vitamin A with other chemical compounds

• Taken together, these results suggest that RDH11 has a measurable role in regenerating the visual pigment by complementing RDH5 as an 11-cis-RDH in RPE cells, and indicate that an additional unidentified enzyme(s) oxidizes 11-cis-retinol or that an alternative pathway contributes to the retinoid cycle [7].
• The oxidation of 11-cis-retinol to 11-cis-retinal in the retinal pigment epithelium (RPE) represents the final step in a metabolic cycle that culminates in visual pigment regeneration [7].
• In the presence of palmitoyl-CoA and CRALBP, Muller cell membranes synthesized 11-cis-retinyl ester from 11-cis-retinol at a rate which was 20-fold higher than that of all-trans-retinyl ester [9].
• The experimental diets resulted in higher numbers of T and B lymphocytes after VA and carotenoid enrichment, when compared, at various time-points, with the base diet [16].
• Procedures are described for labeling CRALBP with 9-cis-retinaldehyde, 11-cis-retinaldehyde, or 11-cis-retinol [17].

Gene context of Vitamin A

• Altered kinetic parameters were observed for RDH5 oxidation of 11-cis-retinol bound to rCRALBP mutants M222A, M225A, and W244F, supporting impaired substrate carrier function [18].
• The two critical RPE enzymes in the isomerization pathway are lecithin retinol acyl transferase (LRAT) and isomerohydrolase, which processes all-trans-retinyl esters into 11-cis-retinol [19].
• The almost quantitative extraction of RPE65 from RPE membranes has little or no effect on in vitro LRAT and isomerohydrolase activities in quantitative enzymatic assays using RPE membranes, suggesting that RPE65 may not have an important role to play in the enzymatic processing of all-trans-retinol into 11-cis-retinol in vitro [19].
• Cellular retinaldehyde-binding protein (CRALBP) carries 11-cis-retinol or 11-cis-retinaldehyde as endogenous ligands and may function as a substrate carrier protein that modulates interaction of these retinoids with visual cycle enzymes [20].
• Proteomic analyses of the isolated apical RPE demonstrated the presence of CRALBP, EBP50, 11-cis-retinol dehydrogenase, cellular retinol-binding protein 1, and interphotoreceptor retinoid-binding protein [21].

Analytical, diagnostic and therapeutic context of Vitamin A

• Cellular retinaldehyde-binding protein from retina purifies with two endogenous ligands which cochromatograph on high performance liquid chromatography with 11-cis-retinaldehyde and 11-cis-retinol and occur in a ratio of approximately 3:1, respectively [22].
• When IRBP is bound to saturating amounts of its endogenous ligands, all-trans- or 11-cis-retinol, its sedimentation behavior is unchanged, and the same types of particles are visualized by electron microscopy as with the free protein; however, a greater proportion of the molecules are bent [23].
• In this report, an animal model for this disease, 11-cis-rdh-/- mice, was used to investigate the flow of retinoids after a bleach, and microsomal membranes from the retinal pigment epithelium of these mice were employed to characterize remaining enzymatic activities oxidizing 11-cis-retinol [1].

References