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evolution
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RDHs that catalyze the interconversion of retinal and retinol involved in rhodopsin turnover are members of the family of short chain dehydrogenase/reductases
evolution
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all three proteins (Rdh11/12-like 1-3) include conserved signatures of the SDR family, such as cofactor binding (TGXXXGXG), the catalytic mechanism (YXXXK), and the structural integrity (NVG or NAG) patterns. Japanese eel Rdh11/12-like 1 clusters with piscine Rdh11 and Rdh12, however the cluster is formed outside that of mammalian Rdh11 and Rdh12. In contrast, Rdh11/12-like 2 and Rdh11/12-like 3 form a clade with putative European eel Rdh11s and Rdh12s outside that of mammalian and piscine Rdh11/Rdh12
evolution
enzyme RDH10 belongs to the 16C family of the short-chain dehydrogenase/reductase (SDR) superfamily. Most members of the SDR16C family (except for DHRS3) exhibit higher binding affinities for NAD(H) as cofactor, whereas members of the SDR7C family prefer NADP(H). The NAD(H)-dependent oxidoreductases usually function in the oxidative direction in intact cells, whereas the NADP(H)-dependent enzymes function in the reductive direction
evolution
enzyme RDH10 belongs to the 16C family of the short-chain dehydrogenase/reductase (SDR) superfamily. Most members of the SDR16C family (except for DHRS3) exhibit higher binding affinities for NAD(H) as cofactor, whereas members of the SDR7C family prefer NADP(H). The NAD(H)-dependent oxidoreductases usually function in the oxidative direction in intact cells, whereas the NADP(H)-dependent enzymes function in the reductive direction
evolution
human retinol dehydrogenase 11 RDH11 belongs to the short-chain dehydrogenases/ reductases (SDR) family
evolution
retinol dehydrogenase 11 (RDH11) is a member of the short-chain dehydrogenase/reductase (SDR) superfamily of proteins. A mild reduction in retinoic acid signaling is observed in RDH11-null testis
evolution
retinol dehydrogenase-10 (RDH10) is a member of the short-chain dehydrogenase/reductase family
evolution
retinol dehydrogenases (RDHs) are members of the short chain dehydrogenases/reductases (SDR) family of enzymes. The SDRs are typically 250-350 amino acids in length and have a relatively low sequence similarity of about 15-30%. Common to all SDRs is the highly conserved Rossman fold, which is composed of a central beta-sheet flanked by 3-4 alpha-helices, forming the cofactor binding site. The SDRs have two conserved domains: the cofactor binding site (GXXXGXG) and the catalytic site (YXXXK)
evolution
the enzyme belongs to the the short-chain dehydrogenase/reductase (SDR) superfamily, NAD(P)-dependent enzymes, and short-chain dehydrogenase/reductase 16C family (SDR16C)
evolution
RDH11 is co-expressed with BCO1 in several mouse tissues, and the retinaldehyde reductase activity of RDH11 is conserved in the mouse enzyme
malfunction
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generation of Rdh13 knockout mice. No obvious difference in phenotype or function between Rdh13 knockout and wild-type mice. But in Rdh13-/- mice subjected to intense light exposure, the photoreceptor outer-plus-inner-segment and outer nuclear layer are dramatically shorter, and the amplitudes of a- and b-waves under scotopic conditions are significantly attenuated. Increased expression levels of CytC, CytC-responsive apoptosis proteinase activating factor-1 and caspases 3, and other mitochondria apoptosis-related genes, e.g. nuclear factor-kappa B P65 and B-cell lymphoma 2-associated X protein, are observed in Rdh13-/- mice
malfunction
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loss-of-function mutations of RDH12 cause retinal degeneration in some forms of Leber congenital amaurosis. Outer segments of rods deficient in Rdh12 show no altered phenotype. Following exposure to light, a leak of retinoids from outer to inner segments is detected in rods from both wild-type and knock-out mice. In cells lacking Rdh8, EC 1.1.1.105, or Rdh12, this leak is mainly all-trans-retinal, overview. Retinal reductase activity is lost in RDH8-deficient mutants
malfunction
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Rdh10 null mutant mouse embryos exhibit dorsal pancreas agenesis and a hypoplastic ventral pancreas with retarded tubulogenesis and branching. Rdh10 null mutant mouse embryos exhibit dorsal pancreas agenesis and a hypoplastic ventral pancreas with retarded tubulogenesis and branching
malfunction
cyclic-light-reared Rdh8-/- knockout mice show elevated levels of all-trans retinal, contributing to RPE lipofuscin formation and accumulation. Lipofuscin accumulates in the retinal pigment epithelium (RPE) of Rdh8-/- mice
malfunction
fetal mouth movement defects are correlated with cleft palate, cleft palate in retinoid deficiency results from a lack of fetal mouth movement. Mouse embryos deficient in retinoic acid (RA) have mispatterned pharyngeal nerves and skeletal elements that block spontaneous fetal mouth movement in utero. Embryos with deficient retinoid signaling are generated by stagespecific inactivation of retinol dehydrogenase 10 (Rdh10), a gene crucial for the production of RA during embryogenesis. Rdh10+ denotes the wild-type allele, Rdh10delta denotes a targeted knockout null allele with exon 2 deleted, and Rdh10flox is a floxed allele in which exon 2 is excised upon exposure to Cre recombinase thereby converting to Rdh10delta. Disruption of RA production at different embryonic stages can produce a variety of phenotypes, analysis of palate morphology in Rdh10flox/+ control and Rdh10delta/flox mutant embryos, overview
malfunction
mice lacking RDH10 either in cone photoreceptors, Müller cells, or the entire retina show normal cone photoresponses in all RDH10-deficient mouse lines. Their cone-driven dark adaptation both in vivo and in isolated retina is unaffected, indicating that RDH10 is not required for the function of the retina visual cycle. In transgenic mice overexpressing RDH10 ectopically in rod cells, rod dark adaptation is unaffected and transgenic rods are unable to use cis-retinol for pigment regeneration
malfunction
microsomes isolated from the testes and livers of Rdh11-/- mice fed a regular diet exhibit a 3 and 1.7fold lower rate of all-trans-retinaldehyde conversion to all-trans-retinol, respectively, than the microsomes of wild-type littermates. Testes and livers of Rdh11-/- mice fed a vitamin A-deficient diet have about 35% lower levels of all-trans-retinol than those of wild-type mice. Oxidative NAD+-dependent retinol dehydrogenase activity is not affected by inactivation of the rdh11 gene, while similarly to testis microsomes, liver microsomes lacking RDH11 show a lower rate (1.7fold) of retinaldehyde reduction. In lungs and intestines, the microsomal retinaldehyde reductase activities are comparable between RDH11-null mice and their wild-type littermates
malfunction
mutagenesis and targeted gene knockout studies in mice confirm that a functional RDH10 is critical for survival until embryonic day 11.5 (E11.5), as Rdh10-/- embryos can be rescued by maternal supplementation of retinaldehyde from E7.5 to E11.5. Genetic disruption of murine Rdh10 gene results in a marked reduction in retinoic acid (RA) synthesis that leads to numerous developmental abnormalities. RDH10-deficient embryos display defects in axial extension and embryonic turning, abnormal hindbrain and craniofacial patterning, agenesis of posterior pharyngeal arches, perturbed somitogenesis, hypoplastic forelimb buds, and abnormal organogenesis of multiple systems, including heart and vasculature, lungs, and gastrointestinal tract. Embryos carrying a targeted knockout of Rdh10 died by E12.5, while embryos carrying various mutant alleles survived until E13.5-E15.5, or until late gestation. Testicular cell-specific conditional knockout of Rdh10 shows that deficiency of RDH10 in both Sertoli and germ cells completely impairs testicular RA signaling in juvenile animals. Spermatogenesis progressively recovers in adult Rdh10 conditional knockout mice, suggesting that RDH10 is not essential for adult spermatogenesis. In mice, targeted knockout of Dhrs3 results in an about 30% increase in RA levels, reduction in the levels of retinol and retinyl esters, and embryonic lethality late in gestation
malfunction
mutations in RDH12 are primarily associated with Leber congenital amaurosis (LCA) type 13, an early onset retinal dystrophy, presenting in early childhood and accounting for approximately 10% of all LCA cases, clinical phenotypes of autosomal recessive RDH12 LCA, overview. One case of a heterozygous variant has also been implicated in autosomal dominant retinitis pigmentosa (RP)
malfunction
mutations in the gene encoding retinol dehydrogenase 10 (Rdh10) lead to craniofacial, limb, and organ abnormalities. This phenotype, called RDH10trex, is caused by the severely reduced ability of mutant RDH10 to oxidize retinol to retinaldehyde, resulting in insufficient RA signaling
malfunction
mutations in the retinol dehydrogenase 12 (RDH12) gene are primarily associated with Leber congenital amaurosis (LCA) type 13, a severe early onset autosomal recessive retinal dystrophy. This is a progressive disorder with significant decline from 10 years of age, which leads to complete blindness in adulthood. RDH12-LCA is characterized by macular atrophy, which extends peripherally in a variegated pattern corresponding to the retinal vasculature, and midperipheral pigmentary retinopathy. A heterozygous deletion (F254Lfs*24 ) in retinol dehydrogenase 12 (RDH12) causes familial autosomal dominant retinitis pigmentosa. Mutation E260R, a single base pair deletion resulting in a frameshift and premature termination, causes a milder late onset (average age of diagnosis is 28.5 years) retinitis pigmentosa (RP) phenotype, with intraretinal bone spicule pigmentation and attenuation of retinal arterioles. Phenotypes, overview
malfunction
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Rdh8-/- Rdh12-/- double knockout mice show that Rdh8 accounts for 70% of all-trans RDH activity. Rdh12-/- mice display normal retinal morphology at 6 weeks of age. There is no significant difference in rhodopsin levels, indicating efficient regeneration of the chromophore. No difference in all-trans RDH activity in dissected retinae or isolated rod outer segments (ROS) between wild-type and Rdh12-/- mice is observed, suggesting that other enzymes may be compensating for the loss of Rdh12 activity. Knockout mice do show a delayed dark adaptation and accumulation of all-trans retinal after bleaching, indicating an important role of RDH12 under conditions of excess illumination. Retinal homogenates show decreased all-trans retinal reduction, and increased A2E levels. Rdh8-/- Rdh12-/- double knockouts also show mild light-dependent retinal degeneration, with delayed dark adaptation and reduced all-trans RDH activity with a build-up of all-trans retinal, a subsequent accumulation of toxic A2E is observed. Double knockout mice regenerate the visual pigment in vivo and triple knockout Rdh8-/- Rdh12-/- Rdh5-/- mice also have the ability to regenerate 11-cis retinal
malfunction
shRNA-mediated RDH10 knockdown induces glioma cell cycle arrest, impairs glioma cell proliferation in vitro, and promotes glioma apoptosis. RDH10 knockdown significantly represses several key cancer pathways including TWEAK, TNFR1 and P53. RDH10 knockdown inhibits glioma cell growth by down-regulating the TWEAK-NF-kappaB axis
malfunction
the cofactor binding mutants, RDH10 G43A/G47A/G49A-HA and DHRS3 G49A/G51A-FLAG, retain the capacity to form complexes with wild-type protein partners. Similarly, active site mutants, RDH10 Y210A-HA and DHRS3 Y188A-FLAG, retain the capacity to form complexes with wild-type protein partners. Thus, catalytically active proteins are not necessary for complex formation
malfunction
isolated retinas from Rgr+/+ and Rgr-/- mice are exposed to continuous light, and cone photoresponses are recorded. Cones in Rgr-/- retinas lose sensitivity at a faster rate than cones in Rgr+/+ retinas
malfunction
isolated retinas from Rgr+/+ and Rgr-/- mice are exposed to continuous light, and cone photoresponses are recorded. Cones in Rgr-/- retinas lose sensitivity at a faster rate than cones in Rgr+/+ retinas
malfunction
isolated retinas from Rgr+/+ and Rgr-/- mice are exposed to continuous light, and cone photoresponses are recorded. Cones in Rgr-/- retinas lose sensitivity at a significantly faster rate than cones in Rgr+/+ retinas. A similar effect is seen in Rgr+/+ retinas following treatment with alpha-aminoadipic acid. These results indicate that maintenance and recovery of cone sensitivity in isolated mouse retinas requires a light-driven visual cycle that depends on RGR opsin. Thus, ciliary photoreceptors of vertebrates, like the rhabdomeric photoreceptors of invertebrates, can use light itself to regenerate visual pigment
malfunction
microsomes isolated from the testes and livers of Rdh11-/- mice fed a regular diet exhibited a 3 and 1.7fold lower rate of all-trans-retinaldehyde conversion to all-trans-retinol, respectively, than the microsomes of wild-type littermates. Testes and livers of Rdh11-/- mice fed a vitamin A-deficient diet have about 35% lower levels of all-trans-retinol than those of wild-type mice the conversion of beta-carotene to retinol via retinaldehyde as an intermediate appeared to be impaired in the testes of Rdh11-/-/retinol-binding protein 4-/- (Rbp4-/-) mice, which lack circulating holo RBP4 and rely on dietary supplementation with beta-carotene for maintenance of their retinoid stores. Overnight starvation results in a decrease in the amount of RDH11 in livers of fasted mice. Gene expression pattern indicates a mild reduction in retinoic acid signaling in RDH11-null testis. The oxidative NAD+-dependent retinol dehydrogenase activity is not affected by inactivation of the Rdh11 gene. The conversion of retinaldehyde to retinol in whole mouse embryonic fibroblasts (MEFs) lacking RDH11 occurs at a slower rate than in wild-type MEFs
malfunction
RDH10 is not required for the function of the retina visual cycle. Transgenic mice expressing RDH10 ectopically in rod cells show, that rod dark adaptation is unaffected by the expression of RDH10 and transgenic rods are unable to use cis-retinol for pigment regeneration. Lack of phenotype of mice lacking RDH10 in the entire retina
malfunction
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loss-of-function mutations of RDH12 cause retinal degeneration in some forms of Leber congenital amaurosis. Outer segments of rods deficient in Rdh12 show no altered phenotype. Following exposure to light, a leak of retinoids from outer to inner segments is detected in rods from both wild-type and knock-out mice. In cells lacking Rdh8, EC 1.1.1.105, or Rdh12, this leak is mainly all-trans-retinal, overview. Retinal reductase activity is lost in RDH8-deficient mutants
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malfunction
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generation of Rdh13 knockout mice. No obvious difference in phenotype or function between Rdh13 knockout and wild-type mice. But in Rdh13-/- mice subjected to intense light exposure, the photoreceptor outer-plus-inner-segment and outer nuclear layer are dramatically shorter, and the amplitudes of a- and b-waves under scotopic conditions are significantly attenuated. Increased expression levels of CytC, CytC-responsive apoptosis proteinase activating factor-1 and caspases 3, and other mitochondria apoptosis-related genes, e.g. nuclear factor-kappa B P65 and B-cell lymphoma 2-associated X protein, are observed in Rdh13-/- mice
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metabolism
interaction of selenoprotein F (SELENOF) with retinol dehydrogenase 11 (RDH11) implying a role of selenoprotein F in vitamin A metabolism. Selenoprotein F has been reported to play important roles in oxidative stress, endoplasmic reticulum (ER) stress, and carcinogenesis. Both of selenoprotein F and RDH11 might reduce all-trans-retinaldehyde into all-trans-retinol, but overexpressed selenoprotein F and RDH11 inhibit the enzyme activity of each other
metabolism
the enzyme is involved in retinoic acid biosynthesis, overview. Retinoic acid (RA)-mediated transcriptional feedback loops upregulate the expression of the reductive enzyme DHRS3 and downregulate the expression of the oxidative enzyme RDHE2 in response to an increase in retinoic acid levels. Members of two families of SDRs are involved in the regulation of RA homeostasis, SDR16C and SDR7C. Regulation of the flux from retinol to retinaldehyde
metabolism
the enzyme is involved in retinoic acid biosynthesis, overview. Retinoic acid (RA)-mediated transcriptional feedback loops upregulate the expression of the reductive enzyme DHRS3 and downregulate the expression of the oxidative enzyme RDHE2 in response to an increase in retinoic acid levels. Members of two families of SDRs are involved in the regulation of RA homeostasis, SDR16C and SDR7C. Regulation of the flux from retinol to retinaldehyde
metabolism
the oxidation of all-trans-retinol to all-trans-retinal represents the first and rate-limiting step of the all-trans-retinoic acid (RA) synthesis pathway and it is the target of mechanisms that fine-tune RA levels within the cell. RDH10 is one enzyme responsible for the oxidation of all-trans-retinol to all-trans-retinaldehyde, and together with the all-trans-retinaldehyde reductase DHRS3 forms an oligomeric protein complex. The resulting retinoid oxidoreductase complex (ROC) is bifunctional and has the capacity to regulate steady-state levels of the direct precursor of RA, all-trans-retinaldehyde. By coupling retinol dehydrogenase and retinaldehyde reductase activities, an elegant system is formed that can fine-tune steady-state levels of all-trans-retinaldehyde, and consequently RA, concentrations within the cell. DHRS3 is a critical regulator of RA synthesis. Formation of ROC influences the catalytic properties of both RDH10 and DHRS3 subunits
metabolism
the oxidation of all-trans-retinol to all-trans-retinal represents the first and rate-limiting step of the all-trans-retinoic acid (RA) synthesis pathway and it is the target of mechanisms that fine-tune RA levels within the cell. RDH10 is one enzyme responsible for the oxidation of all-trans-retinol to all-trans-retinaldehyde, and together with the all-trans-retinaldehyde reductase DHRS3 forms an oligomeric protein complex. The resulting retinoid oxidoreductase complex (ROC) is bifunctional and has the capacity to regulate steady-state levels of the direct precursor of RA, all-trans-retinaldehyde. By coupling retinol dehydrogenase and retinaldehyde reductase activities, an elegant system is formed that can fine-tune steady-state levels of all-trans-retinaldehyde, and consequently RA, concentrations within the cell. Formation of ROC influences the catalytic properties of both RDH10 and DHRS3 subunits
metabolism
retinaldehyde can be produced in the cells by the oxidation of retinol or by the cleavage of beta-carotene at its central double bond (15,15') catalyzed by cytosolic BCO1. In rodents, cleavage of beta-carotene to retinaldehyde with subsequent conversion of retinaldehyde to retinol occurs mainly in the small intestine. RDH11 is essential for the maintenance of retinol levels in testis of mice on beta-carotene diet
physiological function
Rdh11 is able to efficiently detoxify 4-hydroxynonenal in cells. Rdh11 protects against 4-hydroxynonenal modification of proteins and 4-hydroxynonenal-induced apoptosis in HEK-293 cells
physiological function
Rdh12 is able to efficiently detoxify 4-hydroxynonenal in cells, most probably through its ability to reduce it to a nontoxic alcohol. Cells expressing Rdh12 show significantly less formation of Michael adducts with lysine, histidine, or cysteine residues of proteins thereby inhibiting their physiological functions. Microsomes from retinas of Rdh12 knockout mice form significantly more Michael adducts with microsomal proteins in the presence of 4-hydroxynonenal than wild-type. RDH12 also protects against light-induced apoptosis of photoreceptors
physiological function
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RDH12 activity in the photoreceptor inner segments is also key enzyme function. RDH12 in inner segments can protect vital cell organelles against aldehyde toxicity caused by an intracellular leak of all-trans-retinal, as well as other aldehydes originating both inside and outside the cell
physiological function
DHRS3 activity requires the presence of retinol dehydrogenase RDH10 to display its full catalytic activity. The retinol dehydrogenase activity of RDH10 is reciprocally activated by retinaldehyde reductase DHRS3. At E13.5, DHRS3-null embryos have 4fold lower levels of retinol and retinyl esters, but only slightly elevated levels of retinoic acid. The membrane-associated retinaldehyde reductase and retinol dehydrogenase activities are decreased by 4- and 2fold, respectively, in Dhrs3-/- embryos, and Dhrs3-/- mouse embryonic fibroblasts exhibit reduced metabolism of both retinaldehyde andretinol. Neither RDH10 nor DHRS3 has to be itself catalytically active to activate each other
physiological function
energy status regulates all-trans-retinoic acid biosynthesis at the rate-limiting step, catalyzed by retinol dehydrogenases. Six h after re-feeding, isoform Rdh10 expression is decreased 4563% in liver, pancreas, and kidney, relative to mice fasted 16 h. All-trans-retinoic acid in the liver is decreased 44% 3 h after reduced Rdh expression. Oral gavage with glucose or injection with insulin decreases Rdh10 mRNA 50% or greater in mouse liver
physiological function
the retinol dehydrogenase activity of RDH10 is activated by retinaldehyde reductase DHRS3. In turn, DHRS3 requires the presence of retinol dehydrogenase RDH10 to display its full catalytic activity. Neither RDH10 nor DHRS3 has to be itself catalytically active to activate each other
physiological function
the retinol dehydrogenase activity of RDH10 is reciprocally activated by retinaldehyde reductase DHRS3. At E13.5, DHRS3-null embryos have 4fold lower levels of retinol and retinyl esters, but only slightly elevated levels of retinoic acid. The membrane-associated retinaldehyde reductase and retinol dehydrogenase activities are decreased by 4- and 2fold, respectively, in Dhrs3-/- embryos, and Dhrs3-/- mouse embryonic fibroblasts exhibit reduced metabolism of both retinaldehyde andretinol. Neither RDH10 nor DHRS3 has to be itself catalytically active to activate each other
physiological function
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the enzyme accelerates erythroid cell proliferation by upregulating the STAT5 signaling pathway
physiological function
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the enzyme affects dorsal pancreas development and participates in the terminal differentiation of endocrine cells
physiological function
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all-trans retinal in mouse photoreceptors is reduced predominantly by Rdh8 and Rdh12. Rdh8 and Rdh12 were responsible for over 98% of all-trans RDH activity, withRdh8 accounts for 70% of all-trans RDH activity. The majority of all-trans retinal is reduced by Rdh8 in the outer segments, but some all-trans retinal can leak into the inner segments, where it is reduced by Rdh12. The role of RDH12 in the visual cycle is minimal, but possibly plays a protective role in the clearance of alltrans retinal in periods of intense illumination. Another possible role of RDH12 is protection against toxic lipid peroxidation products, like nonanal and 4-HNE, produced from the oxidative attack of polyunsaturated fatty acids in lipid membranes. A buildup of either all-trans retinal or lipid peroxidation products is damaging to photoreceptors. All-trans retinal accumulation leads to the production of toxic N-retinylidene-N-retinylethanolamine (A2E), and lipid peroxidation products are inherently toxic. RDH12 appears to have two possible roles. RDHs do not appear to be necessary for the regeneration of the visual pigment in mice, but are needed for clearance of all-trans retinal in periods of excess illumination. It is possible that murine RDHs compensate for each other
physiological function
bis-retinoids are a major component of lipofuscin that accumulates in the retinal pigment epithelium (RPE) in aging and age-related macular degeneration (AMD). Bis-retinoids are known to originate from retinaldehydes required for the light response of photoreceptor cells, relative contributions of the chromophore, 11-cis retinal, and photoisomerization product, all-trans retinal, are analyzed, overview. In photoreceptor outer segments, all-trans retinal, but not 11-cis retinal, is reduced by retinol dehydrogenase 8 (RDH8). The reductase activity of RDH8 keeps in check the generation of bis-retinoids from all-trans retinal released by photoactivated rhodopsin. There is no significant increase in lipofuscin precursor fluorescence in wild-type mouse rods following light
physiological function
enzyme retinol dehydrogenase 10 (Rdh10) is crucial for the production of retinoic acid (RA) during embryogenesis, its function is necessary for spontaneous fetal mouth movement that facilitates palate shelf elevation. Proper retinoid signaling and pharyngeal patterning are crucial for the fetal mouth movement needed for palate formation. Vitamin A metabolism and RA production are essential for viability in the early organogenesis stages of development
physiological function
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Japanese eel retinol dehydrogenases 11/12-like 1-3 (Rdh11/12-like 1-3) are 17-oxosteroid reductases (EC 1.1.1.51) involved in sex steroid synthesis. Catalysis of the conversion of A4 to T and E1 to E2 is performed by recombinant Rdh11/12-like 1
physiological function
pigment regeneration is critical for the function of cone photoreceptors in bright and rapidly-changing light conditions. This process is facilitated by the recently-characterized retina visual cycle, in which Müller cells recycle spent all-trans-retinol visual chromophore back to 11-cis-retinol. This 11-cis-retinol is oxidized selectively in cones to the 11-cis-retinal used for pigment regeneration. Retinol dehydrogenase 10 (RDH10) is responsible for the oxidation of 11-cis-retinol in the cone visual cycle, but RDH10 is not the dominant retina 11-cis-RDH, overview. Cone RDH10 is not required for normal cone dark adaptation
physiological function
RDH11 is an enzyme for the reduction of all-trans-retinaldehyde to all-trans-retinol (vitamin A). It is involved in the retinal pigment epithelium (RPE) during the retinoid visual cycle. Interaction of selenoprotein F (SELENOF) with retinol dehydrogenase 11 (RDH11) is analyzed by yeast two-hybrid system and determination of production of retinol. The production of retinol is decreased by SELENOF overexpression, resulting in more retinaldehyde
physiological function
retinol dehydrogenase 11 (RDH11) is a microsomal short-chain dehydrogenase/reductase that recognizes all-trans- and cis-retinoids as substrates and prefers NADPH as a cofactor. RDH11 contributes to the oxidation of 11-cis-retinol to 11-cis-retinaldehyde during the visual cycle in the eye's retinal pigment epithelium. The intestinal microsomes produce two products within the short 15-min incubations with retinaldehyde: retinol and retinyl esters. This suggests that, in the intestinal microsomes, the retinaldehyde reductase activity is coordinated with the retinol esterifying activity, possibly to ensure a highly efficient processing of retinaldehyde into retinyl esters for packaging into chylomicrons. RDH11 is essential for the maintenance of retinol levels in testis of mice on beta-carotene diet, and RDH11 is essential for the maintenance of retinol levels in liver and testis of mice during dietary vitamin A deficiency
physiological function
retinol dehydrogenase 12 (RDH12) is an NADPH-dependent retinal reductase that functions as part of the visual cycle, involving a series of enzymatic reactions that regenerates the visual pigment, 11-cis retinal, overview of the visual cycle and the role of RDH12. A number of RDHs are involved in the visual cycle, and vary in substrate and coenzyme specificity. RDH12 functions as a retinal reductase, with highest activity towards all-trans retinal, followed by 11-cis retinal. Enzyme RDH12 has also been shown to convert dihydrotestosterone (DHT) to androstanediol, suggesting a possible involvement in steroid metabolism. RDH12 can also act on medium chain aldehydes, produced from lipid peroxidation of unsaturated fatty acids metabolising the lipid derived medium chain aldehyde nonanal, and inhibiting the reduction of all-trans retinal in RDH12 transfected HEK-293 cells, indicating that RDH12 can protect cells from nonanal induced toxity, but RDH12 does not protect cells against 4-hydroxynonenal (4-HNE), the most abundant lipid peroxidation product, although HEK-293 cells stably transfected with RDH12 do protect from 4-HNE-induced cell death
physiological function
retinol dehydrogenase-10 (RDH10) plays an important role in retinoic acid (RA) synthesis, and it promotes development and progression of human glioma via the TWEAK-NF-kappaB axis. RDH10 is highly expressed in human gliomas, and its expression correlates with tumor grade and patient survival times, RDH10 expression is associated with development and progression of human glioma. RDH10 is overexpressed in human gliomas and predicts a high grade and poor prognosis. RDH10 regulates the cell cycle progression, as its loss causes an S and G2/M phase arrest, RDH10 regulates expression of glioma genes, it affects expression of genes involved in cancer, apoptosis, growth and proliferation, motility, and cell cycle
physiological function
the enzyme is involved in retinoic acid biosynthesis, overview. The NAD(H)-dependent oxidoreductases usually function in the oxidative direction in intact cells, whereas the NADP(H)-dependent enzyme function in the reductive direction. RDH10 acts as a high-affinity retinol dehydrogenase with a preference for NAD+ as cofactor. DHRS3 acts as an NADP(H)-dependent retinaldehyde reductase
physiological function
the enzyme is involved in retinoic acid biosynthesis, overview. The NAD(H)-dependent oxidoreductases usually function in the oxidative direction in intact cells, whereas the NADP(H)-dependent enzymes function in the reductive direction. RDH10 acts as a high-affinity retinol dehydrogenase with a preference for NAD+ as cofactor
physiological function
the retinoid oxidoreductase complex (ROC) is bifunctional and has the capacity to regulate steady-state levels of the direct precursor of RA, all-trans-retinaldehyde. By coupling retinol dehydrogenase and retinaldehyde reductase activities, an elegant system is formed that can fine-tune steady-state levels of all-trans-retinaldehyde, and consequently RA, concentrations within the cell. Formation of ROC influences the catalytic properties of both RDH10 and DHRS3 subunits. Catalytically active enzymes are not necessary for complex formation. As the rate-limiting step of RA synthesis, the conversion of all-trans-retinol to all-trans-retinaldehyde is a target of mechanisms that regulate RA synthesis. ROC, consisting of the retinol dehydrogenase RDH10 and the retinaldehyde reductase DHRS3, is a critical component of RA synthesis regulation
physiological function
the retinoid oxidoreductase complex (ROC) is bifunctional and has the capacity to regulate steady-state levels of the direct precursor of RA, all-trans-retinaldehyde. By coupling retinol dehydrogenase and retinaldehyde reductase activities, an elegant system is formed that can fine-tune steady-state levels of all-trans-retinaldehyde, and consequently RA, concentrations within the cell. Formation of ROC influences the catalytic properties of both RDH10 and DHRS3 subunits. DHRS3 is a critical regulator of RA synthesis. Catalytically active enzymes are not necessary for complex formation. As the rate-limiting step of RA synthesis, the conversion of all-trans-retinol to all-trans-retinaldehyde is a target of mechanisms that regulate RA synthesis. ROC, consisting of the retinol dehydrogenase RDH10 and the retinaldehyde reductase DHRS3, is a critical component of RA synthesis regulation
physiological function
cone-specific 11-cis-RDH is likely to be important in regulating access to the retina visual cycle. Retinol dehydrogenase 10, RDH10 (UniProt ID Q8VCH7), is not the dominant retina 11-cis-RDH. Cone RDH10 is not required for the normal function of dark-adapted cones and for normal cone dark adaptation, as well as for the retina visual cycle
physiological function
RDH11 contributes to the oxidation of 11-cis-retinol to 11-cis-retinaldehyde during the visual cycle in the eye's retinal pigment epithelium. In mouse testis and liver, RDH11 functions as an all-trans-retinaldehyde reductase essential for the maintenance of physiological levels of all-trans-retinol under reduced vitamin A availability. RDH11 is essential for the maintenance of retinol levels in testis of mice on beta-carotene diet
physiological function
the retinal RPE G-protein-coupled receptor, RGR opsin, and retinol dehydrogenase-10 (Rdh10) convert all-trans-retinol to 11-cis-retinol during exposure to visible light. RGR opsin is a non-visual opsin in intracellular membranes of RPE and Müller cells. The interaction between RGR and Rdh10 is specific. RGR opsin is a critical component of the Müller-cell visual cycle, and that regeneration of cone visual pigment can be driven by light, role of RGR opsin in the regeneration of cone visual pigment. Cones are responsible for vision in bright light and operate at high rates of opsin photoisomerization. Recovery of cone sensitivity is shown to be limited by chromophore supply. Only 11-cis-retinal (11cRAL) can regenerate bleached opsin. Coupled photoisomerization and oxidoreduction of vitamin A by RGR opsin and Rdh10, overview
physiological function
the retinal RPE G-protein-coupled receptor, RGR opsin, and retinol dehydrogenase-10 (Rdh10) convert all-trans-retinol to 11-cis-retinol during exposure to visible light. RGR opsin is a non-visual opsin in intracellular membranes of RPE and Müller cells. The interaction between RGR and Rdh10 is specific. RGR opsin is a critical component of the Müller-cell visual cycle, and that regeneration of cone visual pigment can be driven by light, role of RGR opsin in the regeneration of cone visual pigment. Cones are responsible for vision in bright light and operate at high rates of opsin photoisomerization. Recovery of cone sensitivity is shown to be limited by chromophore supply. Only 11-cis-retinal (11cRAL) can regenerate bleached opsin. Coupled photoisomerization and oxidoreduction of vitamin A by RGR opsin and Rdh10, overview
physiological function
the retinal RPE G-protein-coupled receptor, RGR opsin, and retinol dehydrogenase-10 (Rdh10) convert all-trans-retinol to 11-cis-retinol during exposure to visible light. RGR opsin is a non-visual opsin in intracellular membranes of RPE and Müller cells. The interaction between RGR and Rdh10 is specific. RGR opsin is a critical component of the Müller-cell visual cycle, and that regeneration of cone visual pigment can be driven by light, role of RGR opsin in the regeneration of cone visual pigment. Cones are responsible for vision in bright light and operate at high rates of opsin photoisomerization. Recovery of cone sensitivity is shown to be limited by chromophore supply. Only 11-cis-retinal (11cRAL) can regenerate bleached opsin. Coupled photoisomerization and oxidoreduction of vitamin A by RGR opsin and Rdh10, overview
physiological function
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RDH12 activity in the photoreceptor inner segments is also key enzyme function. RDH12 in inner segments can protect vital cell organelles against aldehyde toxicity caused by an intracellular leak of all-trans-retinal, as well as other aldehydes originating both inside and outside the cell
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additional information
in RDH12, the cofactor binding site is located at positions 46-52 and the catalytic site at positions 200-204
additional information
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in RDH12, the cofactor binding site is located at positions 46-52 and the catalytic site at positions 200-204