Disease relevance of RDH5

• The vaccinia virus H3L homolog was identified as the capripoxvirus P32 antigen [1].
• The ELISA was specific for capripoxvirus as only sera from sheep infected with capripoxvirus but not orf or vaccinia virus reacted with the capripoxvirus P32 antigen [1].
• The P32 proteins of SPV and LSDV were expressed in Escherichia coli as a fusion protein with a poly-histidine tag and affinity purified on metal binding resin [1].
• In the present study, we use immunogold electron microscopy to evaluate the subcellular distribution of P32 protein (gC1q-R) in cultured cell lines and in rat tissues embedded in the acrylic resin LR Gold. Immunogold labeling of Raji lymphoma, CHO, human fibroblasts, HeLa and B-SC-1 cells shows reactivity primarily within mitochondria [2].

High impact information on RDH5

• Here, we demonstrate three novel enzymatic activities in cone-dominant ground-squirrel and chicken retinas: an all-trans-retinol isomerase, an 11-cis-retinyl-ester synthase, and an 11-cis-retinol dehydrogenase [3].
• Ligand interactions determine the physiological role of CRALBP in the RPE where the protein is thought to function as a substrate carrier for 11-cis-retinol dehydrogenase in the synthesis of 11-cis-retinal for visual pigment regeneration [4].
• We propose that p32 is the stereospecific 11-cis retinol dehydrogenase, which catalyzes the final step in the biosynthesis of 11-cis retinaldehyde, the universal chromophore of visual pigments [5].
• Overexpression of p32 in Cos cells produced a membrane-bound stereospecific 11-cis retinol dehydrogenase, active in the presence of NAD+ as cofactor but not in the presence of NADP [5].
• Intracellular localization and membrane topology of 11-cis retinol dehydrogenase in the retinal pigment epithelium suggest a compartmentalized synthesis of 11-cis retinaldehyde [6].

Biological context of RDH5

• Although their amino acid sequences are 54% identical, these enzymes have different cofactor specificities: rat retinol dehydrogenase uses NADP+, while cow 11-cis retinol dehydrogenase uses NAD+ [7].

Anatomical context of RDH5

• In this work we demonstrate that a majority of 11-cis retinol dehydrogenase is associated with the smooth ER in retinal pigment epithelial cells and that the enzyme is an integral membrane protein, anchored to membranes by two hydrophobic peptide segments [6].
• Localization of P32 protein (gC1q-R) in mitochondria and at specific extramitochondrial locations in normal tissues [2].
• Subcellular distribution of 11-cis retinol dehydrogenase activity in bovine pigment epithelium [8].

Associations of RDH5 with chemical compounds

• The 11-cis-retinol dehydrogenase (11-cis-RoDH) gene encodes the short-chain alcohol dehydrogenase responsible for 11-cis-retinol oxidation in the visual cycle [9].
• We have compared directly the kinetic properties of recombinant human and mouse 9cRDH with those of bovine 11cRDH for 9-cis- and 11-cis-retinol and investigated the inhibitory properties of 13-cis-retinoic acid on each of these enzymes [10].
• This conclusion is inconsistent with earlier literature indicating that 11cRDH is expressed solely in the eye and does not utilize 9-cis-retinol as a substrate [10].

Other interactions of RDH5

• It is unlikely that the 11-cis retinol dehydrogenase from pigment epithelium is directly involved in providing 11-cis retinaldehyde from rhodopsin regeneration, but it may serve to make available 11-cis retinaldehyde from rhodopdsin, digested in phagocytized rod sacs, for the synthesis of visual pigment by the visual cells [11].

Analytical, diagnostic and therapeutic context of RDH5

• The full-length P32 protein contained a transmembrane region close to the carboxy terminus and was membrane associated but could be solubilised in detergent and used as trapping antigen in an antibody detection ELISA [1].
• Western immunoblots show that the polyclonal antibody to P32 (gC1q-R) used in this study reacts specifically with a 32-kDa protein in both purified pancreatic zymogen granules and in mitochondria, and no other proteins are reactive [2].
• A capripoxvirus detection PCR and antibody ELISA based on the major antigen P32, the homolog of the vaccinia virus H3L gene [1].

References