23, 25, 26-trihydroxycholecalciferol. A 25-hydroxycholecalciferol-26,23-lactone precursor.
Ontology highlight
ABSTRACT:
SUBMITTER: Napoli JL
PROVIDER: S-EPMC1158566 | biostudies-other | 1982 Jul
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Studies of 25-hydroxyvitamin D(3)-24-hydroxylase (CYP24A1) have demonstrated that it is a bifunctional enzyme capable of the 24-hydroxylation of 1alpha,25-(OH)(2)D(3), leading to the excretory form, calcitroic acid, and 23-hydroxylation, culminating in 1alpha,25-(OH)(2)D(3)-26,23-lactone. The degree to which CYP24A1 performs either 23- or 24-hydroxylation is species-dependent. In this paper, we show that the human enzyme that predominantly 24-hydroxylates its substrate differs from the opossum enzyme that 23-hydroxylates it at only a limited number of amino acid residues. Mutagenesis of the human form at a single substrate-binding residue (A326G) dramatically changes the regioselectivity of the enzyme from a 24-hydroxylase to a 23-hydroxylase, whereas other modifications have no effect. Ala-326 is located in the I-helix, close to the terminus of the docked 25-hydroxylated side chain in a CYP24A1 homology model, a result that we interpret indicates that substitution of a glycine at 326 provides extra space for the side chain of the substrate to move deeper into the pocket and place it in a optimal stereochemical position for 23-hydroxylation. We discuss the physiological ramifications of these results for species possessing the A326G substitution, as well as implications for optimal vitamin D analog design.
| S-EPMC1937525 | biostudies-literature
Project description:Broiler breeder hens with efficient feed conversion rate under restricted feed intake (R-hens) or allowed unlimited access to feed (Ad-hens) progressed with cardiac functional failure and suffered early sudden death. A supplement of 69 μg 25-hydroxycholecalciferol (25-OH-D3)/kg feed improved heart health and rescued livability in both R- and Ad-hens throughout laying stage (26-60 wks). Improvements occurred through cardiac hypertrophic remodeling, reduced arrhythmias, and pathological cues. Here, we further demonstrated consistently decreased circulating and cardiac IL-6 and IL-1β levels in conjunction with reduced cardiac chemoattraction and leukocyte infiltration by 25-OH-D3 in Ad-hens and in R-hens at later time points (35 and 47 wks) (p < 0.05). Supplemental 25-OH-D3 also ameliorated cardiac fibrosis, endoplasmic reticulum (ER) stress, and autophagy, mostly in Ad-hens, as both collagen content and expression of COL3A1, as well as CCAAT box binding enhancer homologous protein (CHOP) and activating transcription factor 6 (ATF6), were consistently decreased, and suppression of microtubule-associated protein 1 light Chain 3 beta (LC3B) and Sequestosome 1 (SQSTM1) was rescued at 35 and 47 wks (p < 0.05). Vitamin D receptor-NF-κB signaling was shown to mediate these beneficial effects. The present results demonstrate that ER stress and autophagic processes along the sequence from inflammation to fibrotic changes contribute to pathological cardiac remodeling and functional compromise by Ad-feed intake. 25-OH-D3 is an effective anti-inflammatory and anti-fibrotic supplement to ameliorate cardiac pathogenesis in broiler breeder hens.
| S-EPMC7664627 | biostudies-literature
Project description:The crystal structure of the title compound, C31H45BrO5·CH2Cl2, prepared in six steps from diosgenin, confirmed that the configurations of the stereogenic centers, positions 20S and 25R, remain unchanged during the reaction. The six-membered A, B and C rings have chair conformations. The five-membered ring D has an envelope conformation (with the methyl-substituted C atom fused to ring C as the flap) and the six-membered dihydro-pyran ring E adopts a twist-boat conformation. In the crystal, mol-ecules are linked via C-H?O and C-H?Cl hydrogen bonds, the latter involving the dichloro-methane solvent mol-ecule, forming a three-dimensional supra-molecular network.
| S-EPMC3588813 | biostudies-other
Project description:Past immunological studies in broilers focused on juveniles within the rapid pre-slaughter growth period and may not reflect adult immune responses, particularly in breeders managed with chronic feed restriction (R). The study aimed to assess innate immune cell functions in respect to R vs. ad libitum (Ad) feed intake in breeder hens with and without dietary 25-hydroxycholecalciferol (25-OH-D3) supplementation. Ad-feed intake consistently suppressed IL-1β secretion, respiratory burst, and cell livability in peripheral heterophils and/or monocytes along the feeding trial from the age of 51 to 68 weeks. Supplemental 25-OH-D3 repressed IL-1β secretion and respiratory burst of both cells mostly in R-hens, but promoted monocyte phagocytosis, chemotaxis, and bacterial killing activity in Ad-hens in accompany with relieved hyperglycemia, hyperlipidemia, and systemic inflammation. Overnight cultures with leukocytes from R-hens confirmed the differential effects of 25-OH-D3 to rescue immune functions altered by glucose and/or palmitic acid exposure. Studies with specific inhibitors further manifested the operative mechanisms via glucolipotoxicity in a cell type- and function-dependent manner. The results concluded no predominant changes between R- vs. Ad-feed intake on leukocyte defense against pathogens despite some differential differences, but supplemental 25-OH-D3 exerts more pronounced effects in Ad-hens.
| S-EPMC8230489 | biostudies-literature
Project description:Albumin is responsible for the transport of 25-hydroxycholecalciferol in the Capuchin monkey. This was confirmed by gel filtration, analytical polyacrylamide-disc-gel electrophoresis, polyacrylamide-gel isoelectric focusing and a competitive protein-binding assay. Association constants of the serum transport proteins of a New and an Old World monkey towards 25-hydroxycholecalciferol were calculated; the transport protein in the New World monkey has a lower affinity for the vitamin D metabolite than the transport protein in the Old World primate.
| S-EPMC1172344 | biostudies-other
Project description:Leg problems often result from the rapid weight gain and poor bone quality in modern ducks, leading to a high risk of fractures and continuous pain. We hypothesized that improving bone quality in combination with delaying weight gain via a low nutrient density (LND) diet probably reverses these skeletal abnormalities. Studies indicated that 25-hydroxycholecalciferol (25-OH-D3), a vitamin D3 metabolite, is effective in treating bone-related disorders. Therefore, Exp. 1 evaluated the effects of 25-OH-D3 on tibial mass of meat ducks. Male meat ducklings were fed a standard nutrient density diet (containing a regular vitamin regimen) without or with 25-OH-D3 at 0.069 mg/kg for 35 d. The results showed that 25-OH-D3 supplementation improved the mineral content, microarchitecture and mechanical properties of tibias, and this companied by a decreased serum bone resorption marker and a concomitant decrement in osteoclast-specific marker genes expression. Subsequently, Exp. 2 was conducted to examine the impacts of 25-OH-D3 incorporating an LND diet on tibial quality of ducks under 2 different vitamin regimens (regular and high). Ducklings were allocated to a 2 × 2 factorial arrangement with 2 kinds of vitamin premixes and without or with 25-OH-D3 at 0.069 mg/kg in LND diets. The high premix had higher levels of all vitamins except biotin than the regular premix. The results demonstrated that high vitamin diets exhibited more significant effects than regular vitamin diets on inhibiting bone turnover and increasing minerals deposition. Tibial mineral content, microarchitecture, and strength of birds under the regular vitamin regimen were increased by 25-OH-D3 supplementation; However, these positive effects were not observed in ducks under the high vitamin regimen. To conclude, 25-OH-D3 supplementation improves tibial mass by suppressing osteoclast-mediated bone resorption in meat ducks, and this positive impact only was observed in regular but not high vitamin regimen when birds fed an LND diet.
| S-EPMC7750870 | biostudies-literature
Project description: Not available
| S-EPMC9585422 | biostudies-literature
Project description:Genetic selection and intensive nutrition for increased growth rate in meat-type ducks has resulted in an imbalance between pectorales increment and sternal mass, which is detrimental to productivity and welfare. Reducing body weight and increasing sternal mass probably reverses these adverse effects. Therefore, 2 experiments (Expt.) were conducted to investigate the effects of 25-hydroxycholecalciferol (25-OH-D3), a vitamin D3 metabolites, on sternal mass. In Expt. 1, 512 1-day-old male ducks were randomly assigned to 4 low-nutrient density diets and received following treatments in a 2 × 2 factorial arrangement: (i) NRC or China Agricultural industry standards (NY/T) vitamin premixes and (ii) 0.069 mg/kg 25-HyD in feed or not. At 49 D of age, regardless of 25-OH-D3, NY/T vitamin regimen inhibited bone turnover and consequently increased sternal trabecular bone volume and mineral deposition compared with NRC vitamin premix. Supplementing 25-OH-D3 to NRC but not NY/T vitamin regimen significantly improved sternal microarchitecture and mineral content, which companied by decreased serum bone resorption markers concentration, as well as downregulation of the gene expressions of osteoclast differentiation and activity. In Expt. 2, 256 1-day-old male ducks were fed a standard nutrient density diet contained NRC vitamin premix with 0 or 0.069 mg/kg of 25-OH-D3. Results also showed that 25-OH-D3 treatment significantly improved sternal mineral accumulation and microarchitecture, along with decreasing osteoblast and osteoclast numbers in bone surface, declining serum bone turnover markers levels, and increasing serum Ca concentration. Collectively, these findings indicated that the dietary administration of 25-OH-D3 increased sternal mass in NRC vitamin diet by suppressing bone resorption in 49-day-old meat duck.
| S-EPMC7587744 | biostudies-literature
Project description:A supplement of 69 ?g 25-hydroxycholecalciferol (25-OH-D3)/kg feed increased livability in feed restricted (R-hens) broiler breeder hens by 9.9% and by 65.6% in hens allowed ad libitum feed intake (Ad-hens) in a feeding trial from age 26-60 weeks. Hens with higher bodyweight and/or adiposity suffered sudden death (SD) earlier in conjunction with compromised heart rhythms and over-ventilation. In the study with the same flock of hens, we demonstrate that 25-OH-D3 improved hen's livability and heart health by ameliorating systemic hypoxia, acidosis, and cardiac pathological hypertrophy through calcineurin-NFAT4c signaling and MHC- expression in association with reduced plasma triacylglycerol and hepatic steatosis and fibrosis (p < 0.05). In contrast to live hens sampled at 29, 35, and 47 weeks, SD hens exhibited severe cardiac hypertrophy that was either progressive (Ad-groups) or stable (R-groups). Actual and relative liver weights in SD hens from any group declined as the study progressed. Heart weight correlated significantly to total and relative liver weights in SD-hens of both R- and Ad-groups. In contrast to normal counterparts sampled at 35 and 47 weeks, R-hens exhibiting cardiac hypertrophy experienced severe hypoxia and acidosis, with increased bodyweight, absolute and relative weights of liver and heart, hepatic and plasma triacylglycerol content, and cardiac arrhythmia (p < 0.05). The present results demonstrate that pathological cardiac hypertrophy and functional failure are causative factors of SD and this pathogenic progression is accelerated by hepatopathology, particularly during the early age. Increased feed efficiency with rapid gains in BW and fat increase hens' risk for hypoxia, irreversible cardiac hypertrophy, and arrhythmias that cause functional compromise and SD. Additional supplementation of 69 mg/kg feed of 25-OH-D3 to the basal diet is effective to ameliorate cardiac pathogenesis and prevent SD in broiler breeder hens.
| S-EPMC6826734 | biostudies-literature
Project description:Vitamin D deficiency has been linked to numerous health problems, including those resulting from disturbed calcium-phosphorus homeostasis, and neuropsychiatric and autoimmune disorders. Nearly one-third of the global population has suboptimal levels of vitamin D, according to epidemiological data. Vitamin D status is usually determined by measuring serum 25(OH)D, but, for decades, serum 25(OH)D measurement has been hampered by a lack of standardization. There have been many recent initiatives to develop reference substances and methods for measuring vitamin D and its metabolites, and re-evaluating the optimal values. It was also suggested that alternative biological samples could also be used, such as hair, since it has been established that lipophilic substances, such as corticosteroids, can also be found in hair. The purpose of this study was to determine the correlation between 25(OH)D3 concentrations in serum and hair, and other demographic features in 26 healthy Caucasian young adult volunteers. The determination of 25(OH)D3 and cholecalciferol was carried out using liquid chromatography coupled with mass spectrometry (LC-MS) from blood and hair samples taken at two timepoints separated by nine weeks. In the hair samples of 18 out of 26 subjects, 25(OH)D was detected at a mean (±SEM) concentration of 17.07 ± 5.375 pg/mg at the first sampling time, and 58.90 ± 25.97 pg/mg at the second sampling time. A multiple linear regression analysis revealed no effects of gender, body mass index, supplementation, or sun exposure on hair 25(OH)D3 concentrations, but supplementation and sun exposure significantly increased serum 25(OH)D3 concentrations. In addition, serum and hair 25(OH)D3 concentrations did not correlate; however, there was a strong correlation between the two sampling times for serum 25(OH)D3 concentrations. In conclusion, this study confirmed that 25(OH)D3 could be detected in human hair, but its use as a biomarker warrants further investigations since no link was found between serum 25(OH)D3 concentrations, supplementation, sun exposure, and hair 25(OH)D3 concentrations levels.
| S-EPMC9140052 | biostudies-literature