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| Retinol, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family that is found in food and used as a dietary supplement. Retinol or other forms of vitamin A are needed for vision, cellular development, maintenance of skin and mucous membranes, immune function and reproductive development. Dietary sources include fish, dairy products, and meat. As a supplement it is used to treat and prevent vitamin A deficiency, especially that which results in xerophthalmia. It is taken by mouth or by injection into a muscle. As an ingredient in skin-care products, it is used to reduce wrinkles and other effects of skin aging.
Retinol at normal doses is well tolerated. High doses may cause enlargement of the liver, dry skin, and hypervitaminosis A. High doses during pregnancy may harm the fetus. The body converts retinol to retinal and retinoic acid, through which it acts.
Retinol was discovered in 1909, isolated in 1931, and first made in 1947. It is on the World Health Organization's List of Essential Medicines. Retinol is available as a generic medication and over the counter. In 2021, vitamin A was the 298th most commonly prescribed medication in the United States, with more than 500,000 prescriptions.
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Read full article at Wikipedia
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InChI=1S/C20H30O/c1- 16(8-6-9-17(2)13-15-21)11-12-19-18(3)10-7-14-20(19,4)5/h6,8-9,11-13,21H,7,10,14-15H2,1-5H3/b9-6+,12-11+,16-8+,17-13+ |
| FPIPGXGPPPQFEQ-OVSJKPMPSA-N |
| C\C(=C/CO)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Taxus chinensis
(NCBI:txid29808)
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See:
PubMed
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Pandanus tectorius
(NCBI:txid4726)
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See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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See:
DOI
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Homo sapiens
(NCBI:txid9606)
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Found in
blood
(UBERON:0000178).
See:
Geigy Scientific Tables, 8th Rev edition, pp. 165-177. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp., Basel, Switzerland c1981-1992.
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Homo sapiens
(NCBI:txid9606)
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Found in
saliva
(UBERON:0001836).
See:
Dame, ZT. et al. (2014) The Human Saliva Metabolome (manuscript in preparation)
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human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
(via retinol )
plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
metabolite
Any intermediate or product resulting from metabolism. The term 'metabolite' subsumes the classes commonly known as primary and secondary metabolites.
(via vitamin A )
fat-soluble vitamin (role)
Any vitamin that dissolves in fats and are stored in body tissues. Unlike the water-soluble vitamins, they are stored in the body for long periods of time and generally pose a greater risk for toxicity when consumed in excess.
(via vitamin A )
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View more via ChEBI Ontology
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retinol
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WHO MedNet
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rétinol
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WHO MedNet
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retinol
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WHO MedNet
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retinolum
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WHO MedNet
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(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-ol
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IUPAC
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(all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol
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HMDB
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all-trans retinol
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ChemIDplus
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all-trans-Retinol
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KEGG COMPOUND
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all-trans-retinol
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UniProt
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all-trans-retinyl alcohol
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ChemIDplus
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all-trans-vitamin A
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ChemIDplus
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all-trans-vitamin A alcohol
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NIST Chemistry WebBook
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retinol (vit A)
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DrugCentral
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trans-retinol
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HMDB
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vitamin A
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KEGG COMPOUND
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vitamin A alcohol
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ChemIDplus
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Vitamin A1
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KEGG COMPOUND
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vitamin A1
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ChEBI
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vitamin A1 alcohol
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ChemIDplus
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Alphalin
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ChemIDplus
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Aquasol A
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KEGG DRUG
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Chocola A
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ChemIDplus
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2831
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DrugCentral
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393012
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ChemSpider
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C00031437
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KNApSAcK
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C00473
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KEGG COMPOUND
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C17276
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KEGG COMPOUND
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CPD-13524
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MetaCyc
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D00069
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KEGG DRUG
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D06543
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KEGG DRUG
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DB00162
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DrugBank
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HMDB0000305
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HMDB
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LMPR01090001
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LIPID MAPS
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Retinol
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Wikipedia
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RTL
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PDBeChem
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| View more database links |
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11103-57-4
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CAS Registry Number
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ChemIDplus
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247497
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Gmelin Registry Number
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Gmelin
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403040
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Beilstein Registry Number
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Beilstein
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68-26-8
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CAS Registry Number
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ChemIDplus
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68-26-8
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CAS Registry Number
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NIST Chemistry WebBook
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Hu Z, Bang YJ, Ruhn KA, Hooper LV (2019)
Molecular basis for retinol binding by serum amyloid A during infection.
Proceedings of the National Academy of Sciences of the United States of America 116, 19077-19082 [PubMed:31484771]
[show Abstract]
Serum amyloid A (SAA) proteins are strongly induced in the liver by systemic infection and in the intestine by bacterial colonization. In infected mice, SAA proteins circulate in association with the vitamin A derivative retinol, suggesting that SAAs transport retinol during infection. Here we illuminate a structural basis for the retinol-SAA interaction. In the bloodstream of infected mice, most SAA is complexed with high-density lipoprotein (HDL). However, we found that the majority of the circulating retinol was associated with the small fraction of SAA proteins that circulate without binding to HDL, thus identifying free SAA as the predominant retinol-binding form in vivo. We then determined the crystal structure of retinol-bound mouse SAA3 at a resolution of 2.2 Å. Retinol-bound SAA3 formed a novel asymmetric trimeric assembly that was generated by the hydrophobic packing of the conserved amphipathic helices α1 and α3. This hydrophobic packing created a retinol-binding pocket in the center of the trimer, which was confirmed by mutagenesis studies. Together, these findings illuminate the molecular basis for retinol transport by SAA proteins during infection. | Žabčíková S, Mikysek T, Červenka L, Sýs M (2018)
Electrochemical Study and Determination of All-trans-Retinol at Carbon Paste Electrode Modified by a Surfactant.
Food technology and biotechnology 56, 337-343 [PubMed:30510477]
[show Abstract]
The oxidation mechanism of all-trans-retinol (vitamin A1) and its several esters in non-aqueous, aqueous organic mixture, and pure aqueous media was investigated by cyclic voltammetry. The oxidation occurred in several irreversible steps. The calculated highest density of electrons in retinoid molecules which are delocalized over carbon atoms of the five conjugated double bonds (C5-C14) was found in the part of the molecule involved in oxidation processes. The most sensitive oxidation peak (at +0.8 V vs. Ag/AgCl) was used for development of new direct voltammetric method based on differential pulse voltammetry for the determination of retinol at carbon paste electrode modified with surfactant sodium dodecyl sulfate (CPE/SDS). The results show that 30% (by mass) of modifier SDS exhibited optimal sensitivity and shape of voltammograms. Compared to commonly used glassy carbon electrode (GCE), the CPE/SDS showed significant progress in the retinol electroanalysis. The linear ranges for retinol determination were 1.5·10-6-1.8·10-4 M for CPE/SDS and 4.4·10-6-7.0·10-4 M for GCE with the detection limits of 1.3·10-6 and 4.6·10-7 M, respectively. | Nossoni Z, Assar Z, Yapici I, Nosrati M, Wang W, Berbasova T, Vasileiou C, Borhan B, Geiger J (2014)
Structures of holo wild-type human cellular retinol-binding protein II (hCRBPII) bound to retinol and retinal.
Acta crystallographica. Section D, Biological crystallography 70, 3226-3232 [PubMed:25478840]
[show Abstract]
Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a noncanonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided. | Chen C, Koutalos Y (2010)
Rapid formation of all-trans retinol after bleaching in frog and mouse rod photoreceptor outer segments.
Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology 9, 1475-1479 [PubMed:20697621]
[show Abstract]
All-trans retinol is formed in the outer segments of vertebrate rod photoreceptors from the reduction of the all-trans retinal released by photoactivated rhodopsin. The reduction requires NADPH and is therefore dependent on metabolic input. In metabolically intact photoreceptors, a large increase in rod outer segment fluorescence, attributed to the fluorescence of all-trans retinol, follows rhodopsin photoactivation. The fluorescence increase is biphasic, including a rapid and a slow component. In metabolically compromised cells, there is a much smaller fluorescence increase following rhodopsin photoactivation, but it too contains a rapid component. We have measured the fluorescence signal in single living frog and mouse rod photoreceptors, and have characterized its dependence on the wavelengths of light selected for excitation and for collecting emission. We find that in metabolically intact cells, the excitation and emission properties of both the rapid and slow components of the fluorescence signal are in close agreement with those of all-trans retinol fluorescence. In metabolically compromised cells, however, the signal can only partially be due to all-trans retinol, and most of it is consistent with all-trans retinal. The results suggest that in the outer segments of living rod photoreceptors there is rapid release of all-trans retinal, which in metabolically intact cells is accompanied by rapid conversion to all-trans retinol. | Thiyagarajan B, Valivittan K (2009)
Effect of all-trans retinol on in vitro development of preimplantation buffalo embryos.
Animal : an international journal of animal bioscience 3, 385-392 [PubMed:22444309]
[show Abstract]
Vitamin A is a well-known antioxidant and is essential for embryonic development, growth and differentiation. Oxidative stress is involved in the etiology of defective embryo development. The present study evaluated whether the presence of all-trans retinol (0, 1, 2, 5 and 10 μM) in maturation medium or embryo culture medium would enhance the developmental competence of preimplantation buffalo embryos in vitro. In experiment I, cumulus oocytes complex were matured with varying concentrations of all-trans retinol. Treatment with 5 μM all-trans retinol improved the blastocyst formation (P < 0.001) when compared with control and significant increase (P < 0.01) in total cell number was observed in 5 μM group when compared with control. Supplementation of all-trans retinol in embryo culture medium for the entire culture period under 5% O2 and 20% O2 was tested in experiments II and III, respectively. Supplementation of 10 μM all-trans retinol under 5% O2, significantly reduced blastocyst formation and cell numbers. Presence of 5 μM all-trans retinol under 20% O2 enhanced the frequency of blastocyst formation and total cell number (P < 0.001) when compared with control. DNA damage of individual embryos cultured under 20% oxygen concentration was measured by the comet assay. Supplementation of 5 μM all-trans retinol significantly reduced the comet tail (P < 0.001) when compared with control. Supplementation of all-trans retinol in embryo culture medium for first 72 h of the 8-day culture period under 5% O2 was tested in experiment IV. Addition of 5 μM all-trans retinol resulted in significant increase in blastocyst rate and total cell number (P < 0.001) when compared with control. Our results demonstrate that addition of all-trans retinol to maturation or embryo culture medium may enhance the developmental competence of buffalo embryos in vitro by enhancing blastocyst formation rate and total cell number. | Chen C, Blakeley LR, Koutalos Y (2009)
Formation of all-trans retinol after visual pigment bleaching in mouse photoreceptors.
Investigative ophthalmology & visual science 50, 3589-3595 [PubMed:19264891]
[show Abstract]
PurposeTo test whether the formation of all-trans retinol limits the regeneration of the visual pigment. all-trans retinol is formed after visual pigment bleaching through the reduction of all-trans retinal in a reaction involving NADPH. This reduction begins the recycling of the chromophore for the regeneration of the visual pigment.MethodsExperiments were performed with dark-adapted, isolated retinas and isolated photoreceptor cells from wild-type and Nrl(-/-) mice. The photoreceptors of Nrl(-/-) mice are conelike and contain only cone pigments. The formation of all-trans retinol after pigment bleaching was measured by quantitative HPLC of retinoids extracted from isolated retinas and by imaging the fluorescence of retinol in photoreceptor outer segments. Experiments were performed at 37 degrees C.ResultsIn rods, the formation of all-trans retinol proceeded with first-order kinetics, with a rate constant of 0.06 +/- 0.02 minute(-1), significantly faster than the reported rate constant for rhodopsin regeneration. In Nrl(-/-) photoreceptors, the formation of all-trans retinol occurred at least 100 times faster than in rods. For both cell types, the fraction of all-trans retinal converted to all-trans retinol at equilibrium is approximately 0.8, indicating the presence of a similar fraction of reduced NADPH.ConclusionsFormation of all-trans retinol does not limit the regeneration of bleached visual pigment. Formation of all-trans retinol in the cone-like Nrl(-/-) photoreceptors is much faster than in rods, consistent with a faster regeneration of the visual pigment after bleaching. Different types of photoreceptors contain a comparable fraction of reduced NADPH to drive the reduction of all-trans retinal. | Jumpsen JA, Brown NE, Thomson AB, Paul Man SF, Goh YK, Ma D, Clandinin MT (2006)
Fatty acids in blood and intestine following docosahexaenoic acid supplementation in adults with cystic fibrosis.
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 5, 77-84 [PubMed:16507353]
[show Abstract]
UnlabelledThe objective of this study was to investigate the effect of docosahexaenoic acid (DHA) supplementation on blood and intestinal DHA levels and lung function in mild/moderately affected adult CF patients with the DeltaF508 genotype.BackgroundCystic Fibrosis (CF) patients often present with plasma fatty acid levels indicating low levels of linoleic (18:2n-6) and docosahexaenoic (22:6n-3) acids and an increased level of arachidonic acid (20:4n-6). Improved dietary fat intake or reducing fat malabsorption with pancreatic enzymes has failed to normalize this biochemical deficiency of DHA.MethodsFive CF patients, aged 18-43, received 70 mg of DHA/kg body weight/d for six weeks. At baseline and at six weeks a physical exam, lung function, 3-day dietary intake, duodenal mucosal biopsy and blood sample were assessed. The blood was analyzed for plasma vitamin A, D and E levels, liver function tests, clinical chemistry (CBC, differential and electrolytes). Plasma and red blood cell fatty acid levels were also analyzed. At three weeks, assessment included a physical exam, lung function test and fasting blood sample (vitamin levels, liver function and clinical chemistry only).ResultsPre- and post-measurements were compared for the four subjects who completed the study. An increase in DHA content (% w/w) was observed in all phospholipid fractions of plasma, red blood cell and mucosal samples. No significant differences in vitamin levels, liver function or lung function were observed.ConclusionsThe study proves the concept that an increase in tissue DHA levels in CF patients can be achieved by supplementing for six weeks with 70 mg/kg/d DHA. | Penniston KL, Tanumihardjo SA (2006)
The acute and chronic toxic effects of vitamin A.
The American journal of clinical nutrition 83, 191-201 [PubMed:16469975]
[show Abstract]
The acute and chronic effects of vitamin A toxicity are well documented in the literature. Emerging evidence suggests that subtoxicity without clinical signs of toxicity may be a growing concern, because intake from preformed sources of vitamin A often exceeds the recommended dietary allowances (RDA) for adults, especially in developed countries. Osteoporosis and hip fracture are associated with preformed vitamin A intakes that are only twice the current RDA. Assessing vitamin A status in persons with subtoxicity or toxicity is complicated because serum retinol concentrations are nonsensitive indicators in this range of liver vitamin A reserves. The metabolism in well-nourished persons of preformed vitamin A, provided by either liver or supplements, has been studied by several research groups. To control vitamin A deficiency, large therapeutic doses are administered in developing countries to women and children, who often are undernourished. Nevertheless, little attention has been given to the short-term kinetics (ie, after absorption but before storage) of a large dose of vitamin A or to the short- and long-term effects of such a dose given to lactating women on serum and breast-milk concentrations of retinol and its metabolites. Moreover, appropriate dosing regimens have not been systematically evaluated to ascertain the quantitative improvement in vitamin A status of the women and children who receive these supplements. The known acute and chronic effects of vitamin A toxicity have been reported previously. However, further research is needed to ascertain the areas of the world in which subclinical toxicity exists and to evaluate its effects on overall health and well-being. | Graham-Maar RC, Schall JI, Stettler N, Zemel BS, Stallings VA (2006)
Elevated vitamin A intake and serum retinol in preadolescent children with cystic fibrosis.
The American journal of clinical nutrition 84, 174-182 [PubMed:16825693]
[show Abstract]
BackgroundPersons with cystic fibrosis (CF) and pancreatic insufficiency (PI) are at risk of vitamin A deficiency because of steatorrhea, despite pancreatic enzyme replacement. Long-standing vitamin A supplementation may increase the risk of vitamin A toxicity.ObjectiveThe aim was to describe the vitamin A intake and serum retinol concentrations of preadolescent children with CF, PI, and mild-to-moderate pulmonary disease, who were cared for under current practice recommendations.DesignThis cross-sectional study evaluated children aged 8.0-11.9 y with CF and PI from 13 US CF centers. Dietary and supplemental vitamin A intakes were compared with the Dietary Reference Intakes (DRIs) for healthy children, CF recommendations, and data from the National Health and Nutrition Examination Survey (NHANES), 1999-2000. Serum retinol concentrations were compared with NHANES data.ResultsThe 73 subjects with CF had a dietary vitamin A intake of 816 +/- 336 microg retinol activity equivalents (165 +/- 69% of the recommended dietary allowance), which was similar to the NHANES value. The supplement intake provided 2234 +/- 1574 microg retinol activity equivalents/d and exceeded recommendations in 21% of the subjects with CF. Total preformed retinol intake exceeded the DRI tolerable upper intake level in 78% of the subjects with CF. The serum retinol concentration was 52 +/- 13 microg/dL (range: 26-98 microg/dL), which was significantly higher than the NHANES value (37 +/- 10 microg/dL; range: 17-63 microg/dL; P < 0.001).ConclusionAlthough supplementation helps to prevent vitamin A deficiency in children with CF and PI, their high vitamin A intakes and serum retinol concentrations suggest that usual care may result in excessive vitamin A intake and possible toxicity that would increase the risk of CF-associated liver and bone complications. | Mills JP, Penniston KL, Tanumihardjo SA (2005)
Extra-hepatic vitamin A concentrations in captive Rhesus (Macaca mulatta) and Marmoset (Callithrix jacchus) monkeys fed excess vitamin A.
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition 75, 126-132 [PubMed:15929633]
[show Abstract]
Recent work examining vitamin A (VA) status of rhesus monkeys (Macaca mulatta) used as models for human biomedical research has revealed subtoxic hepatic VA concentrations. Livers of marmoset monkeys (Callithrix jacchus), another experimental animal, were also high in VA as was serum retinyl ester concentration. Both species consumed common research diets that provided up to four times the amount of VA (retinyl acetate) as currently recommended by the National Research Council. To further define the effects of chronically high dietary VA as found in many human subpopulations, we analyzed lung and kidney tissues from subtoxic rhesus and marmoset monkeys (n = 10 each) for retinol and retinyl esters. Marmoset kidneys contained 0.88 +/- 0.66 micromol VA/g and was nearly the same as hepatic VA at 1.40 +/- 0.44 micromol/g (p = 0.143). In contrast, rhesus kidney VA concentrations were 0.0100 +/- 0.0032 micromol/g, even though liver reserves were 18.8 +/- 6.4 micromol VA/g (p < 0.0001). Lung tissue VA concentrations, 0.0022 +/- 0.0012 and 0.0061 +/- 0.0025 micromol/g for marmosets and rhesus, respectively, were lower as compared with kidney (p < 0.011). Kidney and lung VA in monkeys with adequate, but not excessive, VA stores have not been determined; hence, interpretation of these findings is limited to tissue retinol and retinyl ester profiles and extrapolation from other species rather than direct comparison to "normal" values. | Egeland GM, Berti P, Soueida R, Arbour LT, Receveur O, Kuhnlein HV (2004)
Age differences in vitamin A intake among Canadian Inuit.
Canadian journal of public health = Revue canadienne de sante publique 95, 465-469 [PubMed:15622799]
[show Abstract]
BackgroundInuit traditional food provides ample amounts of preformed vitamin A. However, the dietary transition away from traditional food raises concerns regarding dietary adequacy. Vitamin A is an essential nutrient with inadequate and excessive exposures having adverse effects.ObjectiveTo evaluate total dietary vitamin A intake for Canadian Inuit from market food and traditional food sources and to evaluate retinol concentrations in liver and blubber.MethodsDietary surveys were conducted in 18 communities representing 5 Inuit regions, and traditional food items were evaluated for nutrient content.ResultsAmong those 15-40 years of age, 68% of men and 60% of women had a dietary vitamin A intake below the estimated average requirement (EAR) for retinol activity equivalents (RAE)/day. Among those over 40 years of age, only 11 % of men and 15% of women had a dietary vitamin A intake below the EAR. Young Inuit men had a relative risk of 6.2 (95% CI= 4.5-8.4), and young Inuit women had a relative risk of 4.0 (95% CI= 3.1-5.0) for dietary inadequacy compared to the older Inuit men and women, respectively. The median retinol content of liver of ringed seal, caribou, and fish were comparable to levels observed in market food liver. Liver was less frequently consumed by those 15-40 years of age than among older Inuit.DiscussionSub-optimal vitamin A intake is the predominant nutritional concern rather than excessive exposures. Public health education campaigns are needed to improve vitamin A intake among the younger generations of Inuit men and women. | Alberts D, Ranger-Moore J, Einspahr J, Saboda K, Bozzo P, Liu Y, Xu XC, Lotan R, Warneke J, Salasche S, Stratton S, Levine N, Goldman R, Islas M, Duckett L, Thompson D, Bartels P, Foote J (2004)
Safety and efficacy of dose-intensive oral vitamin A in subjects with sun-damaged skin.
Clinical cancer research : an official journal of the American Association for Cancer Research 10, 1875-1880 [PubMed:15041701]
[show Abstract]
PurposePreviously, we reported the results of a Phase III, placebo-controlled trial in 2297 randomized participants with moderately severe actinic keratoses wherein 25000 IU/day vitamin A caused a 32% risk reduction in squamous cell skin cancers. We hypothesized that dose escalation of vitamin A to 50000 or 75000 IU/day would be both safe and more efficacious in skin cancer chemoprevention.Experimental designOne hundred and twenty-nine participants with severely sun-damaged skin on their lateral forearms were randomized to receive placebo or 25000, 50000, or 75000 IU/day vitamin A for 12 months. The primary study end points were the clinical and laboratory safety of vitamin A, and the secondary end points included quantitative, karyometric image analysis and assessment of retinoid and rexinoid receptors in sun-damaged skin.ResultsThere were no significant differences in expected clinical and laboratory toxicities between the groups of participants randomized to placebo, 25000 IU/day, 50000 IU/day, and 75000 IU/day. Karyometric features were computed from the basal cell layer of skin biopsies, and a total of 22600 nuclei from 113 participants were examined, showing statistically significant, dose-response effects for vitamin A at the 25000 and 50000 IU/day doses. These karyometric changes correlated with increases in retinoic acid receptor alpha, retinoic acid receptor beta, and retinoid X receptor alpha at the 50000 IU/day vitamin A dose.ConclusionsThe vitamin A doses of 50000 and 75000 IU/day for 1 year proved safe and equally more efficacious than the 25000 IU/day dose and can be recommended for future skin cancer chemoprevention studies. | Ribaya-Mercado JD, Solomons NW, Medrano Y, Bulux J, Dolnikowski GG, Russell RM, Wallace CB (2004)
Use of the deuterated-retinol-dilution technique to monitor the vitamin A status of Nicaraguan schoolchildren 1 y after initiation of the Nicaraguan national program of sugar fortification with vitamin A.
The American journal of clinical nutrition 80, 1291-1298 [PubMed:15531678]
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BackgroundNicaragua initiated a national program of vitamin A fortification of its domestic sugar supply starting with the 1999-2000 sugarcane harvest.ObjectiveThis study was conducted to document any change in the vitamin A status of a cohort of children during the first year of the program.DesignThe vitamin A status of 21 Nicaraguan schoolchildren (mean age: 6.7 y; range: 5.3-9.3 y) was assessed in March 2000 and in March 2001. Total-body vitamin A stores and liver vitamin A concentrations were estimated with the deuterated-retinol-dilution (DRD) technique at a dose of 5 mg [(2)H(4)]retinyl acetate at baseline and 5 mg [(2)H(8)]retinyl acetate during the repeat test 1 y later. Plasma retinol and carotenoids were measured by HPLC.ResultsMedian total-body vitamin A stores increased from 0.33 to 0.72 mmol (P = 0.0001), liver vitamin A concentrations from 0.52 to 0.78 mumol/g (P = 0.0003), and plasma retinol concentrations increased from 0.97 to 1.17 mumol/L (P = 0.01).ConclusionThe vitamin A status of Nicaraguan schoolchildren improved during the year after the initial distribution of vitamin A-fortified sugar in Nicaragua. | Ribaya-Mercado JD, Solon FS, Fermin LS, Perfecto CS, Solon JA, Dolnikowski GG, Russell RM (2004)
Dietary vitamin A intakes of Filipino elders with adequate or low liver vitamin A concentrations as assessed by the deuterated-retinol-dilution method: implications for dietary requirements.
The American journal of clinical nutrition 79, 633-641 [PubMed:15051608]
[show Abstract]
BackgroundThe vitamin A requirements of elderly humans have not been studied.ObjectiveIn a cross-sectional study of 60-88-y-old men (n = 31) and women (n = 31) in rural Philippines, we assessed the dietary intakes of elders with adequate (> or = 0.07 micromol/g) or low (< 0.07 micromol/g) liver vitamin A concentrations to estimate vitamin A requirements for this age group.DesignTotal-body vitamin A was assessed by the deuterated-retinol-dilution technique; liver vitamin A concentrations were assessed by assuming that liver weight is 2.4% of body weight and that, in this marginally nourished population, 70% of total-body vitamin A is in the liver; serum retinol was measured by HPLC; and dietary intakes were assessed with 3 nonconsecutive 24-h dietary recalls. The mean vitamin A intake + 2 SDs of subjects with adequate liver vitamin A concentrations was used to estimate an acceptable or sufficient vitamin A intake value for elders.ResultsThe mean (+/- SD) vitamin A intakes of the men and women with adequate vitamin A in liver were 135 +/- 86 and 134 +/- 104 microg retinol activity equivalents (RAE)/d, respectively; intakes of the men and women with low vitamin A in liver were 75 +/- 53 and 60 +/- 27 microg RAE/d, respectively. Total-body vitamin A or liver vitamin A but not serum retinol correlated with dietary RAE, preformed vitamin A, beta-carotene, fat, and protein. An estimated acceptable or sufficient dietary vitamin A intake associated with adequate liver vitamin A concentrations in elders is 6.45 microg RAE/kg body wt; for a reference 76-kg man and a 61-kg woman, these values are approximately 500 and 400 microg RAE/d, respectively.ConclusionThe dietary vitamin A intakes of elders with adequate or low liver vitamin A concentrations as estimated by use of the deuterated-retinol-dilution technique are useful for assessing vitamin A requirements. | Sorenson AW, Delhumeau C, Bernstein MS, Costanza MC, Morabia A (2003)
Impact of 'Mad Cow Disease' publicity on trends in meat and total vitamin A consumption in Geneva between 1993 and 2000.
European journal of clinical nutrition 57, 177-185 [PubMed:12548314]
[show Abstract]
BackgroundIn March 1996, revelations about the possible risk for humans of the 'mad cow disease' epidemic had a sudden impact on the diets of European populations.ObjectiveTo assess changes in meat and nutrient intakes in adults living in Geneva, Switzerland from 1993 to 2000.DesignIndependent annual cross-sectional surveys (4047 women and 4092 men total).Main outcome measureDietary habits assessed and compared to baseline (January 1993-April 1996) via validated semi-quantitative food-frequency questionnaire.ResultsWomen beef abstainers increased from 8.9 to 14.9% in late 1996 (P<0.001) and 13.3% in 1997 (P<0.05); among meat consumers, in late 1996 meat/beef intakes declined -10/-12% (both P<0.05). From 1997 to 2000 most intake levels drifted back toward those at baseline, but chicken intakes were significantly (all P<0.05) greater each year (+19% in 2000 (P<0.001). Consistent but less dramatic changes were observed among men. From late 1996 until 2000, liver abstention was significantly (all P<0.05) greater (women from 60 to 78%; men from 61 to 73% in 2000; (both P<0.001). The only nutrient intakes that decreased significantly (all P<0.05) each year from 1997 through 2000 were retinol and total vitamin A women: -22% (P<0.001); -11% (P<0.05) respectively; men: -16% (P<0.001); -10% (P<0.05) respectively, in 2000). Total vitamin A intakes exceeded the dietary reference intake (DRI) for liver eaters (women 185%, men 153%), but were below the DRI for liver abstainers (women 83%; men 66%) in 2000.ConclusionThe decreases in beef and liver consumption since late 1996 led to the discovery of a long-term disparity in the retinol and total vitamin A intakes of liver eaters vs abstainers. | Wieringa FT, Dijkhuizen MA, West CE, Thurnham DI, Muhilal, Van der Meer JW (2003)
Redistribution of vitamin A after iron supplementation in Indonesian infants.
The American journal of clinical nutrition 77, 651-657 [PubMed:12600856]
[show Abstract]
BackgroundDeficiencies of iron and vitamin A are prevalent worldwide. Single-micronutrient supplementation is widely used to combat these deficiencies. However, micronutrient deficiencies often occur concurrently, and there are many interactions between micronutrients.ObjectiveThis study investigated interactions among 3 important micronutrients--iron, vitamin A, and zinc--when they are given as supplements.DesignIn a randomized, double-blind, placebo-controlled supplementation trial, 387 Indonesian infants aged 4 mo were supplemented 5 d/wk for 6 mo with 10 mg Fe, 10 mg Zn, 2.4 mg beta-carotene, 10 mg each of Fe and Zn, 10 mg Zn + 2.4 mg beta-carotene, or placebo. Complete data on micronutrient status, including hemoglobin, ferritin, retinol, zinc, and the modified relative dose response (a measure of liver retinol stores), were available from 256 infants at the end of the study.ResultsIron-supplemented infants had significantly lower plasma retinol concentrations and a significantly higher prevalence of vitamin A deficiency, as defined by a plasma retinol concentration <0.70 micromol/L, than did the non-supplemented infants. In contrast, the modified relative dose response of the iron-supplemented infants indicated greater liver stores of vitamin A. Iron supplementation improved iron status, and zinc supplementation improved zinc status, but beta-carotene supplementation did not significantly improve vitamin A status.ConclusionsIn this study, iron supplementation in infants with marginal vitamin A status led to lower plasma vitamin A concentrations and simultaneously to greater vitamin A liver stores. This implies a redistribution of retinol after iron supplementation, which might induce vitamin A deficiency. Therefore, iron supplementation in infants should be accompanied by measures to improve vitamin A status. | Kieu NT, Yurie K, Hung NT, Yamamoto S, Chuyen NV (2002)
Simultaneous analysis of retinol, beta-carotene and tocopherol levels in serum of Vietnamese populations with different incomes.
Asia Pacific journal of clinical nutrition 11, 92-97 [PubMed:12074187]
[show Abstract]
In this study, we clarified the status of the fat-soluble vitamins retinol and tocopherol, as well as beta-carotene, as antioxidants in the prevention of cardiovascular disease in middle-aged Vietnamese populations with different incomes. In order to measure simultaneously the serum concentrations of retinol, beta-carotene and tocopherol, we carried out high-performance liquid chromatography analysis with three separate detectors. The analytical method was modified, omitting the saponification process, and used a multi-evaporating system with dry ice. This allowed the analysis to proceed more rapidly, use a small amount of serum (40 microL) and be free of hexane contamination to the environment. The analyses reflected an adequate status of vitamin A (serum retinol = 20 microg/dL), but inadequate status of beta-carotene and vitamin E (serum beta-carotene <40 microg/dL; serum tocopherol < 600 microg/dL) in all three Vietnamese populations. As large numbers of Vietnamese subjects were observed with very low serum concentrations of beta-carotene and tocopherol, higher consumptions of green and yellow vegetables, fruits, vegetable oils and other foods rich in vitamin E are recommended for these Vietnamese populations. | Márquez M, Yépez CE, Sútil-Naranjo R, Rincón M (2002)
[Basic aspects and measurement of the antioxidant vitamins A and E].
Investigacion clinica 43, 191-204 [PubMed:12229281]
[show Abstract]
Vitamin E usually works as a biological antioxidant, preventing the oxidation of polyunsaturated fatty acids and proteins, for which it is considered an important protective factor in the development of diseases related to oxidative processes. Beyond its antioxidant properties, it has been involved also in genetic expression, mitochondrial metabolism, cell differentiation and immune system regulation. From the point of view of its antioxidant protection properties, values > or = 1200-1300 micrograms/dL are considered optimum levels (standardized according to plasmatic lipid levels). In relation to the beneficial advantage effects of vitamin E on primary or secondary atherosclerotic disease, data are not conclusive. Vitamin A is part of the organism's defense barrier against free radicals. Its antioxidant mechanism of action includes scavenging of single oxygen and thiol free radicals, and it also could be related to processes that involve genetic expression and cell differentiation. As an antioxidant, vitamin A plasmatic levels > or = 80 micrograms/dL are considered optimal. The highest risk of using this vitamin is related to its acute or chronic toxicity. Quantification of serum vitamin E (alpha tocopherol) and vitamin A (retinol) are made by high performance liquid chromatography (HPLC), method of high precision, sensitivity and reproducibility. | Allen LH, Haskell M (2002)
Estimating the potential for vitamin A toxicity in women and young children.
The Journal of nutrition 132, 2907S-2919S [PubMed:12221269]
[show Abstract]
This paper describes usual intakes of vitamin A from diet plus low dose supplements, reviews methods for assessing vitamin A toxicity and applies a kinetic analysis of vitamin A turnover to estimate the effect of high dose supplements on vitamin A liver stores in infants and young children. In the United States, the 95th percentile of intake by preschoolers from foods and supplements exceeds the tolerable upper level (UL) but is below the no-observed-adverse-effect level (NOAEL). The 95th percentile of vitamin A intake from foods and supplements for nonpregnant, nonlactating women aged 19-30 y also exceeds the UL but is below the NOAEL for women of reproductive age. In low income populations in developing countries, vitamin A intakes of preschoolers and women consuming foods plus low dose supplements can also exceed the UL but are unlikely to exceed the NOAEL. There are few data on which to establish thresholds for excessive vitamin A intake or vitamin A concentrations in tissues. To assess the potential toxicity of the new recommendations (see article by Ross in this issue) for high dose vitamin A supplements for infants and children, we used a kinetic approach to estimate accumulation of the vitamin in liver. The new recommendations are unlikely to result in toxic levels (>300 microg per gram of liver) even if high dose supplements are inadvertently given monthly. The kinetic analysis also illustrates that a constant supply of vitamin A from breast milk (and/or complementary foods) is vital for preventing depletion of liver vitamin A stores between high dose supplements. | Dawson MI (2000)
The importance of vitamin A in nutrition.
Current pharmaceutical design 6, 311-325 [PubMed:10637381]
[show Abstract]
Preformed vitamin A (all-trans-retinol and its esters) and provitamin A (beta-carotene) are essential dietary nutrients that provide a source of retinol. Both retinyl esters and beta-carotene are metabolized to retinol. The retinol-binding proteins on binding retinol provide a means for solubilizing retinol for delivery to target tissues and for regulating retinol plasma concentrations. Oxidation of retinol provides retinal, which is essential for vision, and retinoic acid, a transcription factor ligand that has important roles in regulating genes involved in cell morphogenesis, differentiation, and proliferation. The observations that vitamin A can produce cell and tissue changes similar to those found during neoplastic transformation and that vitamin supplementation can reverse this process indicated a potential role for vitamin A in cancer prevention. Thus far, correlative epidemiological studies on vitamin A use and cancer prevention have produced mixed results, as this review indicates. Apparently, in populations deficient in vitamin A (caused by an inadequate diet or tobacco use), supplementation programs appear to be effective in reducing cancer incidence. In groups already having sufficient dietary or supplemental vitamin A, cancer prevention by added vitamin A may not be particularly effective. The most likely reason for the low efficacy in the latter groups is that feedback mechanisms that increase retinol storage in the liver limit retinol plasma levels; whereas, supplementation at higher doses causes toxicity. In addition to serving as a metabolic source of retinol, beta-carotene, along with other dietary carotenoids, function as antioxidants that can prevent carcinogenesis by decreasing the levels of the free-radicals that cause DNA damage. | Guo Y, Bozic D, Malashkevich VN, Kammerer RA, Schulthess T, Engel J (1998)
All-trans retinol, vitamin D and other hydrophobic compounds bind in the axial pore of the five-stranded coiled-coil domain of cartilage oligomeric matrix protein.
The EMBO journal 17, 5265-5272 [PubMed:9736606]
[show Abstract]
The potential storage and delivery function of cartilage oligomeric matrix protein (COMP) for cell signaling molecules was explored by binding hydrophobic compounds to the recombinant five-stranded coiled-coil domain of COMP. Complex formation with benzene, cyclohexane, vitamin D3 and elaidic acid was demonstrated through increases in denaturation temperatures of 2-10 degreesC. For all-trans retinol and all-trans retinoic acid, an equilibrium dissociation constant KD = 0.6 microM was evaluated by fluorescence titration. Binding of benzene and all-trans retinol into the hydrophobic axial pore of the COMP coiled-coil domain was proven by the X-ray crystal structures of the corresponding complexes at 0.25 and 0.27 nm resolution, respectively. Benzene binds with its plane perpendicular to the pore axis. The binding site is between the two internal rings formed by Leu37 and Thr40 pointing into the pore of the COMP coiled-coil domain. The retinol beta-ionone ring is positioned in a hydrophobic environment near Thr40, and the 1.1 nm long isoprene tail follows a completely hydrophobic region of the pore. Its terminal hydroxyl group complexes with a ring of the five side chains of Gln54. A mutant in which Gln54 is replaced by Ile binds all-trans retinol with affinity similar to the wild-type, demonstrating that hydrophobic interactions are predominant. | Allende LM, Corell A, Madroño A, Góngora R, Rodríguez-Gallego C, López-Goyanes A, Rosal M, Arnaiz-Villena A (1997)
Retinol (vitamin A) is a cofactor in CD3-induced human T-lymphocyte activation.
Immunology 90, 388-396 [PubMed:9155646]
[show Abstract]
Immunomodulatory effects of different retinoids have been demonstrated, both in vivo and in vitro, in different cellular lineages including human and murine thymocytes, human lung fibroblasts, Langerhans' cells, tumoral cells and natural killer (NK) cells; however, any attempt to demonstrate the effect of retinoids on human peripheral blood mononuclear cells (PBMC) resulted in negative results. In the present work, it is shown that retinol and retinoic acid induce a marked increase of proliferation on human PBMC from 32 unrelated healthy individuals, which had previously been stimulated with anti-CD3 antibodies 48 hr before. Serum-free medium, specific retinoid concentration (10(-7) M) and a particular timing of retinol addition to the cultures (48 hr after CD3 stimulation) was necessary clearly to detect this retinol-enhancing effect. The increased proliferative response is specifically mediated via the clonotipic T-cell receptor-CD3 complex and correlates with the up-regulation of certain adhesion/activation markers on the T-lymphocyte surface: CD18, CD45RO and CD25; also Th1-type of cytokines (interleukin-2 and interferon-gamma) are found concordantly increased after retinoid costimulation, both measured by a direct protein measurement and by a specific mRNA increase. In addition, it is shown that the in vitro retinol costimulation is only present in immunodeficient patients who have no defect on CD3 molecules and activation pathway. The fact that retinol costimulate lymphocytes only via CD3 (and not via CD2 or CD28) and the lack of response enhancement in immunodeficients with impaired CD3 activation pathway indicates that retinoids may be used as therapeutic agents in immune system deficiencies that do not affect the clonotypic T-cell receptor. | Boehnlein J, Sakr A, Lichtin JL, Bronaugh RL (1994)
Characterization of esterase and alcohol dehydrogenase activity in skin. Metabolism of retinyl palmitate to retinol (vitamin A) during percutaneous absorption.
Pharmaceutical research 11, 1155-1159 [PubMed:7971717]
[show Abstract]
Retinyl palmitate, a widely used ingredient in cosmetic products, is promoted for its beneficial effects on the appearance of skin. Previous studies suggest that enzymes are available in skin to metabolize this ingredient during skin absorption. Esterase activity hydrolyzes retinyl palmitate to retinol (vitamin A), which is oxidized in many tissues to retinoic acid primarily by alcohol dehydrogenase. The activities of esterase and alcohol dehydrogenase were characterized in hairless guinea pig skin by using flow-through diffusion cells and radiolabeled model compounds (methyl salicylate and benzyl alcohol) previously shown to be metabolized by these enzymes. Methyl salicylate was hydrolyzed by esterase to a greater extent in viable skin than in nonviable skin. Glycine conjugation of salicylic acid and benzoic acid occurred only in viable skin. The metabolism of methyl salicylate and benzyl alcohol occurred to a greater extent in male guinea pig skin than in female guinea pig skin. The percutaneous absorption of both radiolabeled compounds was similar in viable and nonviable skin. About 30 and 18% of topically applied retinyl palmitate were absorbed from an acetone vehicle by hairless guinea pig skin and human skin, respectively. Less than 1% of the applied dose of this lipophilic compound diffused from skin into the receptor fluid. Retinol was the only detectable metabolite of retinyl palmitate in both hairless guinea pig and human skin. In human skin, 44% of the absorbed retinyl palmitate was hydrolyzed to retinol. The use of retinyl palmitate in cosmetic formulations may result in significant delivery of retinol into the skin. | Zanotti G, Ottonello S, Berni R, Monaco HL (1993)
Crystal structure of the trigonal form of human plasma retinol-binding protein at 2.5 A resolution.
Journal of molecular biology 230, 613-624 [PubMed:8464067]
[show Abstract]
The three-dimensional structures of the liganded and unliganded forms of human plasma retinol binding protein (RBP) in the trigonal crystal form have been solved at 2.5 A resolution. The final model of RBP complexed with retinol (holoRBP, space group R3, a = b = 104.0 A, c = 74.4 A) has a crystallographic R factor of 0.176 for 9652 reflections. The unliganded form, obtained through a purification procedure which included steps based on hydrophobic interaction chromatography, crystallized isomorphously with holoRBP and its structure has been refined to an R factor of 0.190 for 9614 reflections. The structure of the trigonal holo protein is quite similar to that of the orthorhombic form: the root-mean-square deviation of all the equivalent alpha-carbons in the two chains is 0.53 A. The structural comparison between the liganded and unliganded forms of RBP in the crystal did not reveal gross conformational changes. The most significant difference between the two forms of the protein is a conformational change involving residues from 34 to 37. In this region, the movements of side-chains of Leu35 and Phe36 are most noticeable. In particular, in the unliganded form the side-chain ring of the latter residue is in the place previously occupied by the alcoholic moiety of retinol. Our data are consistent with a model in which a region comprising these residues and at least part of the opening of the beta-barrel is involved in the recognition between RBP and transthyretin. In the case of the unliganded form, the central cavity, that is occupied by the vitamin in the two human crystalline holoRBPs, is filled by electron density that, at the present resolution, we interpret as solvent. | Zanotti G, Berni R, Monaco HL (1993)
Crystal structure of liganded and unliganded forms of bovine plasma retinol-binding protein.
The Journal of biological chemistry 268, 10728-10738 [PubMed:8496140]
[show Abstract]
The three-dimensional structures of bovine plasma retinol-binding protein (bRBP) complexed with retinol (space group P2(1)2(1)2(1), a = 46.08, b = 49.12, c = 76.10 A) and of the unliganded protein prepared in vitro by extracting retinol with ethyl ether (space group P2(1)2(1)2(1), a = 46.55, b = 48.97, c = 76.87 A) have been solved at 1.9 and 1.7 A resolution, respectively. The final crystallographic R factors are 0.190 for holobRBP and 0.196 for the unliganded bRBP. The model for the bovine holoprotein is quite similar to that of the human protein, with which it exhibits 92% sequence similarity. The root mean square deviation between the alpha-carbons in the two proteins is 0.31 A. The retinol binding site is almost completely preserved. The loops that surround the opening of the beta-barrel are also particularly conserved, in contrast with the presence of several substitutions in parts of the RBP molecule opposite the opening of the calyx that binds retinol. Despite the fact that unliganded bovine RBP was prepared and crystallized using procedures completely different from those used to obtain the unliganded human RBP, the conformational differences between unliganded and liganded forms of bRBP are almost identical to those found previously between the same forms of human RBP. They mainly involve a few residues in the region extending from amino acid residues 32 to 37. Therefore, similar differences are very likely to exist between holoRBP and the physiologically occurring apoprotein. A not yet identified electron density, different in shape and orientation from retinol, also occupies the central cavity of the beta-barrel in the unliganded bRBP, as found for unliganded human RBP. The functional consequences of the conformational change induced by the removal of retinol on the interaction between RBP and transthyretin, coupled with the conservation of the entrance loops of the beta-barrel in mammalian RBPs, are consistent with their participation in molecular interactions. | Norum KR, Blomhoff R (1992)
McCollum Award Lecture, 1992: vitamin A absorption, transport, cellular uptake, and storage.
The American journal of clinical nutrition 56, 735-744 [PubMed:1414975]
[show Abstract]
We discuss vitamin A with emphasis on its absorption, transport, cellular uptake, storage, and intracellular metabolism. Dietary retinyl esters are hydrolyzed to retinol in the intestinal lumen before absorption by enterocytes. Carotenoids are absorbed and then partially converted to retinol in the enterocytes. In enterocytes retinol is esterified before incorporation into chylomicrons together with triacylglycerols. Chylomicrons reach the general circulation by way of the intestinal lymph, and chylomicron remnants are formed in the blood capillaries. The remnants, which contain almost all the absorbed retinol, are cleared by the liver parenchymal cells, and to some extent also by cells in blood, bone marrow, adipose tissue, and spleen. The uptake is most probably mediated via surface receptors for low-density lipoproteins or a low-density lipoprotein-receptor-related protein. In the liver parenchymal cells the retinyl esters are rapidly hydrolyzed to retinol, which binds to retinol-binding protein. Normally, most of the absorbed retinol coming into the liver parenchymal cell is transferred on retinol-binding protein to stellate cells, which store retinol as retinyl esters in lipid droplets. | Cowan SW, Newcomer ME, Jones TA (1990)
Crystallographic refinement of human serum retinol binding protein at 2A resolution.
Proteins 8, 44-61 [PubMed:2217163]
[show Abstract]
Human serum retinol binding protein (RBP) in complex with retinol has been crystallographically refined to an R-factor of 18.1% with 2A resolution data. The protein topology results in an anti-parallel beta-barrel that encapsulates the retinol ligand. A detailed description of the protein and the binding site is provided. Our structural work has helped to define a family of proteins, many of which are carrier proteins for smaller ligand molecules. We describe the structural basis for the conservation of sequence within the family. | Törmä H, Vahlquist A (1990)
Vitamin A esterification in human epidermis: a relation to keratinocyte differentiation.
The Journal of investigative dermatology 94, 132-138 [PubMed:2295828]
[show Abstract]
Keratinocytes from three different layers of epidermis (stratum basale, stratum spinosum, and stratum granulosum/corneum) were shown by high-performance liquid chromatography to contain retinol, 3,4-didehydroretinol and several fatty acyl esters thereof. The concentration of unesterified congeners increased 1.8-2.8 times from the inner to the outer layers of epidermis, while the corresponding increase in fatty acyl esters was 4.0-6.5 times. Together the esters represented 71% of the total vitamin A content in stratum granulosum/corneum as compared to 54% in stratum basale. The in situ synthesis of fatty acyl esters of retinol and 3,4-didehydroretinol (vitamin A2) was studied by addition of [3H]retinol to organ-cultured human breast skin. The radioactive compounds appearing in the epidermis after 48 h were, in order of abundance, retinyl esters, retinol, 3,4-didehydroretinyl esters, and 3,4-didehydroretinol. Studies at the subcellular level demonstrated the highest esterifying activity in the microsomal fraction. The enzyme catalyzing the reaction, acyl CoA:retinol acyltransferase (ARAT; EC 2.3.1.76), had a pH optimum of 5.5-6.0, which differs from that of ARAT in other tissues. ARAT activities in microsomes from different layers of epidermis were similar, but, owing to a presumed pH gradient in upper epidermis, the in vivo esterification of vitamin A may be enhanced in terminally differentiating keratinocytes. The mean ARAT activities in basal cell carcinomas and squamous cell carcinomas were less than 50% of the control values, and the relative amounts of retinyl esters were significantly lower than normal. We suggest that the esterification of vitamin A may also be of importance in relation to pathologic keratinocyte differentiation. | Meyskens FL (1985)
Vitamin a and its derivatives: the retinoids.
Science (New York, N.Y.) 228, 317-318 [PubMed:17790232] |
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