InChI=1S/C28H44O2/c1- 19-10-14-24(29)18-23(19)13-12-22-8-7-17-28(6)25(15-16-26(22)28)20(2)9-11-21(3)27(4,5)30/h9,11-13,20-21,24-26,29-30H,1,7-8,10,14-18H2,2-6H3/b11-9+,22-12+,23-13-/t20-,21+,24+,25-,26+,28-/m1/s1 |
| KJKIIUAXZGLUND-ICCVIKJNSA-N |
| C[C@H](\C=C\[C@H](C)C(C)(C)O)[C@H]1CC[C@H]2\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)CCC1=C |
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human xenobiotic metabolite
Any human metabolite produced by metabolism of a xenobiotic compound in humans.
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 D )
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bone density conservation agent
An agent that inhibits bone resorption and/or favor bone mineralization and bone regeneration. Used to heal bone fractures and to treat bone diseases such as osteopenia and osteoporosis.
nutraceutical
A product in capsule, tablet or liquid form that provide essential nutrients, such as a vitamin, an essential mineral, a protein, an herb, or similar nutritional substance.
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View more via ChEBI Ontology
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(3S,5Z,7E,22E)-9,10-secoergosta-5,7,10,22-tetraene-3,25-diol
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25-Hydroxycalciferol
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HMDB
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25-hydroxyergocalciferol
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LIPID MAPS
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25-hydroxyvitamin D2
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UniProt
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9,10-secoergosta-5,7,10(19),22-tetraene-3β,25-diol
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HMDB
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ercalcidiol
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HMDB
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21343-40-8
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CAS Registry Number
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ChemIDplus
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4716773
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Reaxys Registry Number
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Reaxys
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Gottschlich MM, Mayes T, Khoury J, Kagan RJ (2017)
Clinical Trial of Vitamin D2 vs D3 Supplementation in Critically Ill Pediatric Burn Patients.
JPEN. Journal of parenteral and enteral nutrition 41, 412-421 [PubMed:26059899]
[show Abstract]
BackgroundHypovitaminosis D exists postburn. However, evidence-based guidelines for vitamin D repletion are unknown. This investigation examined differences between D2 and D3 supplementation on outcome in children with burn injuries.MethodsFifty patients with total body surface area burn of 55.7% ± 2.6% and full-thickness injury of 40.8% ± 3.8% were enrolled, ranging in age from 0.7-18.4 years. All participants received multivitamin supplementation per standardized clinical protocol. In addition, 100 IU/kg D2, D3, or placebo was administered daily during hospitalization using a randomized, double-blinded study design. Assay of total 25-hydroxyvitamin D (D25), 1,25-dihydroxyvitamin D (D1,25), 25-hydroxyvitamin D2 (25-OH-D2), 25-hydroxyvitamin D3 (25-OH-D3), and parathyroid hormone (PTH) was performed at 4 preplanned time intervals (baseline, midpoint, discharge, and 1 year postburn). Differences in vitamin D status were compared over time and at each specific study interval.ResultsThere were no significant differences in serum vitamin D levels between groups, but >10% of patients had low D25 at discharge, and percent deficiency worsened by the 1-year follow up for the placebo (75%), D2 (56%), and D3 (25%) groups. There were no statistical differences in PTH or clinical outcomes between treatment groups, although vitamin D supplementation demonstrated nonsignificant but clinically relevant decreases in exogenous insulin requirements, sepsis, and scar formation.ConclusionsThe high incidence of low serum D25 levels 1 year following serious thermal injury indicates prolonged compromise. Continued treatment with vitamin D3 beyond the acute phase postburn is recommended to counteract the trajectory of abnormal serum levels and associated morbidity. | Ziegler TE, Kapoor A, Hedman CJ, Binkley N, Kemnitz JW (2015)
Measurement of 25-hydroxyvitamin D(2&3) and 1,25-dihydroxyvitamin D(2&3) by tandem mass spectrometry: A primate multispecies comparison.
American journal of primatology 77, 801-810 [PubMed:25845705]
[show Abstract]
Vitamin D metabolites are widely studied for their roles in bone health, immune functions, and other potential physiologic roles in humans. However, the optimal blood levels of vitamin D metabolites are still unclear. Various methods for measuring vitamin D metabolites have been used and recently liquid chromatography tandem mass spectroscopy (LC-MS/MS) has been adopted as the gold standard for vitamin D metabolite measurement. Here, we report the use of LC-MS/MS to measure 25-hydroxyvitamin D (25(OH)D(2&3)), and 1,25-dihydroxyvitamin D (1,25(OH)2D(2&3)), in three laboratory nonhuman primate species: common marmoset (Callithrix jacchus), rhesus macaque (Macaca mulatta), and cynomolgus macaque (Macaca fascicularis), and compare them to humans using the same technique. The nonhuman primates showed blood levels for 25(OH)D3 and 1,25(OH)2D3 significantly higher than human values with marmosets having the highest levels. Marmoset samples showed significantly more variability among individuals than those from macaques for both metabolites, but all three nonhuman primate species exhibited large variation within species for both 25(OH)D(2&3) and 1,25(OH)2D(2&3). Marmoset females had significantly lower values than the males for 25(OH)D3, while rhesus males showed a significant decrease in 25(OH)D3 with age. The most striking finding is the variation within species for vitamin D levels even in laboratory primates that have a controlled diet, UV exposure, and in some cases, genetic constraints. Similar variation in 25(OH)D responses to a fixed dose of oral vitamin D supplementation has been reported in humans. We suggest that these species can provide primate models for examining the factors influencing variation in the levels of vitamin D necessary for human and nonhuman primate health. | Mineva EM, Schleicher RL, Chaudhary-Webb M, Maw KL, Botelho JC, Vesper HW, Pfeiffer CM (2015)
A candidate reference measurement procedure for quantifying serum concentrations of 25-hydroxyvitamin D₃ and 25-hydroxyvitamin D₂ using isotope-dilution liquid chromatography-tandem mass spectrometry.
Analytical and bioanalytical chemistry 407, 5615-5624 [PubMed:25967149]
[show Abstract]
The inaccuracy of routine serum 25-hydroxyvitamin D measurements hampers the interpretation of data in patient care and public health research. We developed and validated a candidate reference measurement procedure (RMP) for highly accurate quantitation of two clinically important 25-hydroxyvitamin D metabolites in serum, 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3]. The two compounds of interest together with spiked deuterium-labeled internal standards [d 3-25(OH)D2 and d 6-25(OH)D3] were extracted from serum via liquid-liquid extraction. The featured isotope-dilution LC-MS/MS method used reversed-phase chromatography and atmospheric pressure chemical ionization in positive ion mode. A pentafluorophenylpropyl-packed UHPLC column together with isocratic elution allowed for complete baseline resolution of 25(OH)D2 and 25(OH)D3 from their structural C-3 isomers within 12 min. We evaluated method trueness, precision, potential interferences, matrix effects, limits of quantitation, and measurement uncertainty. Calibration materials were, or were traceable to, NIST Standard Reference Materials 2972. Within-day and total imprecision (CV) averaged 1.9 and 2.0% for 25(OH)D3, respectively, and 2.4 and 3.5% for 25(OH)D2, respectively. Mean trueness was 100.3% for 25(OH)D3 and 25(OH)D2. The limits of quantitation/limits of detection were 4.61/1.38 nmol/L for 25(OH)D3 and 1.46/0.13 nmol/L for 25(OH)D2. When we compared our RMP results to an established RMP using 40 serum samples, we found a nonsignificant mean bias of 0.2% for total 25(OH)D. This candidate RMP for 25(OH)D metabolites meets predefined method performance specifications (≤5% total CV and ≤1.7% bias) and provides sufficient sample throughput to meet the needs of the Centers for Disease Control and Prevention Vitamin D Standardization Certification Program. Graphical abstract Bias assessment using NIST standard reference materials. Legend CDC mean mass fractions (ng/g) ± U 95 (6 replicates per mean). NIST-certified mass fractions (ng/g) ± U 95 from the Certificates of Analysis. | Kwak HS, Chung HJ, Cho DH, Park MH, Ku ES, Park EJ, Oh HJ (2015)
Efficacy of the measurement of 25-hydroxyvitamin D2 and D3 levels by using PerkinElmer liquid chromatography-tandem mass spectrometry vitamin D kit compared with DiaSorin radioimmunoassay kit and Elecsys vitamin D total assay.
Annals of laboratory medicine 35, 263-265 [PubMed:25729734] | Lee D, Garrett TJ, Goldberger BA, Bazydlo LA (2015)
Quantitation of 25-hydroxyvitamin D2 and D3 in serum and plasma by LCMS/MS.
Bioanalysis 7, 167-178 [PubMed:25587834]
[show Abstract]
ObjectiveWe developed and validated an analytical method for quantifying 25-hydroxyvitamin D2 (25OHD2) and 25-hydroxyvitamin D3 (25OHD3) in serum and plasma.MethodsSamples, pretreated with zinc sulfate and methanol, were extracted with hexane. Separation was achieved via UHPLC and 25OHD quantification was accomplished by a triple quadrupole mass spectrometer.ResultsImprecision was 3.6-15.1%CV and bias 88.0-126.0%. Extraction efficiency was 76.5-110.5%, whereas the matrix effect ranged from -46.7 to -32.0%. The method was applied to authentic specimens. The results showed no significant difference between serum and plasma; strong correlation with paired values from an external laboratory; and analyte stability for 15 days.ConclusionThis method provides reliable and accurate measurement of 25OHD for use in clinical practice. | Engelen L, Schalkwijk CG, Eussen SJ, Scheijen JL, Soedamah-Muthu SS, Chaturvedi N, Fuller JH, Stehouwer CD (2015)
Low 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 levels are independently associated with macroalbuminuria, but not with retinopathy and macrovascular disease in type 1 diabetes: the EURODIAB prospective complications study.
Cardiovascular diabetology 14, 67 [PubMed:26025465]
[show Abstract]
BackgroundLow circulating levels of total vitamin D [25(OH)D] and 25(OH)D3 have been associated with vascular complications in few studies on individuals with type 1 diabetes. However, these measures are affected by UV light exposure. Circulating 25(OH)D2, however, solely represents dietary intake of vitamin D2, but its association with complications of diabetes is currently unknown. We investigated the associations between 25(OH)D2 and 25(OH)D3 and the prevalence of albuminuria, retinopathy and cardiovascular disease (CVD) in individuals with type 1 diabetes.MethodsWe measured circulating 25(OH)D2 and 25(OH)D3 in 532 individuals (40 ± 10 years old, 51 % men) with type 1 diabetes who participated in the EURODIAB Prospective Complications Study. Cross-sectional associations of 25(OH)D2 and 25(OH)D3 with albuminuria, retinopathy and CVD were assessed with multiple logistic regression analyses adjusted for age, sex, season, BMI, smoking, HbA1c, total-HDL-cholesterol-ratio, systolic blood pressure, antihypertensive medication, eGFR, physical activity, alcohol intake, albuminuria, retinopathy and CVD, as appropriate.ResultsFully adjusted models revealed that 1 nmol/L higher 25(OH)D2 and 10 nmol/L higher 25(OH)D3 were associated with lower prevalence of macroalbuminuria with ORs (95 % CI) of 0.56 (0.43;0.74) and 0.82 (0.72;0.94), respectively. These vitamin D species were not independently associated with microalbuminuria, non-proliferative and proliferative retinopathy or CVD.ConclusionsIn individuals with type 1 diabetes, both higher 25(OH)D2 and 25(OH)D3 are associated with a lower prevalence of macroalbuminuria, but not of retinopathy and CVD. Prospective studies are needed to further examine the associations between 25(OH)D2 and 25(OH)D3 and the development of microvascular complications and CVD in type 1 diabetes. | Mena-Bravo A, Ferreiro-Vera C, Priego-Capote F, Maestro MA, Mouriño A, Quesada-Gómez JM, Luque de Castro MD (2015)
Quantitative analytical method to evaluate the metabolism of vitamin D.
Clinica chimica acta; international journal of clinical chemistry 442, 6-12 [PubMed:25575651]
[show Abstract]
A method for quantitative analysis of vitamin D (both D2 and D3) and its main metabolites - monohydroxylated vitamin D (25-hydroxyvitamin D2 and 25-hydroxyvitamin D3) and dihydroxylated metabolites (1,25-dihydroxyvitamin D2, 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3) in human serum is here reported. The method is based on direct analysis of serum by an automated platform involving on-line coupling of a solid-phase extraction workstation to a liquid chromatograph-tandem mass spectrometer. Detection of the seven analytes was carried out by the selected reaction monitoring (SRM) mode, and quantitative analysis was supported on the use of stable isotopic labeled internal standards (SIL-ISs). The detection limits were between 0.3-75pg/mL for the target compounds, while precision (expressed as relative standard deviation) was below 13.0% for between-day variability. The method was externally validated according to the vitamin D External Quality Assurance Scheme (DEQAS) through the analysis of ten serum samples provided by this organism. The analytical features of the method support its applicability in nutritional and clinical studies targeted at elucidating the role of vitamin D metabolism. | Freeman J, Wilson K, Spears R, Shalhoub V, Sibley P (2015)
Performance evaluation of four 25-hydroxyvitamin D assays to measure 25-hydroxyvitamin D2.
Clinical biochemistry 48, 1097-1104 [PubMed:26054580]
[show Abstract]
ObjectivesThe ability of current immunoassays to accurately measure equimolar amounts of 25(OH)D2 and 25(OH)D3 has been recently questioned. This study determined serum 25(OH)D2, 25(OH)D3 and total serum 25(OH)D concentrations in healthy vitamin D2-supplemented subjects by isotope dilution liquid chromatography mass spectrometry (ID-LC-MS/MS); and, evaluated the ability of the Siemens, DiaSorin, Roche, and Abbott Vitamin D Total assays to monitor total serum 25(OH)D concentrations compared to an ID-LC-MS/MS method traceable to the National Institute of Standards and Technology (NIST), and that has achieved certification from the Centers for Disease Control and Prevention (CDC) Vitamin D Standardization Certification Program (VDSCP).Design and methodsTwenty (20) healthy adults, with no history of prior vitamin D supplementation were administered oral vitamin D2 (2400IU/day for 6months). Serum samples (140) from baseline and monthly blood draws were tested.ResultsAfter one month, the mean serum 25(OH)D2 concentrations rose from 0.8 to 43.6nmol/L, whereas 25(OH)D3 concentrations declined from 84.0 to 63.4nmol/L; total serum 25(OH)D concentrations rose from 86.6 to 107.0nmol/L. The overall mean bias to ID-LC-MS/MS was -7.1% for the Siemens ADVIA Centaur assay, -15.3% for the DiaSorin LIAISON assay; -8.4% for the Roche ELECSYS assay and -16.3% for the Abbott ARCHITECT assay. Correlation coefficients (r) were 0.94, 0.79, 0.74, and 0.73; the mean bias for baseline [25(OH) D3-containing] versus six-month [25(OH)D2- and 25(OH)D3-containing] samples was -13.4% and -5.7%; -3.5% and 20.3%, 9.6% and -12.1%, and 0.2% and -17.8%, respectively.ConclusionsThe bias results obtained for the Siemens ADVIA Centaur assay and Roche ELECSYS assay were slightly lower than those for the DiaSorin LIAISON assay and the Abbott ARCHITECT assay, but all 25(OH)D assays demonstrated acceptable performance. | Newton-Bishop JA, Davies JR, Latheef F, Randerson-Moor J, Chan M, Gascoyne J, Waseem S, Haynes S, O'Donovan C, Bishop DT (2015)
25-Hydroxyvitamin D2 /D3 levels and factors associated with systemic inflammation and melanoma survival in the Leeds Melanoma Cohort.
International journal of cancer 136, 2890-2899 [PubMed:25403087]
[show Abstract]
Lower 25-hydroxyvitamin D2 /D3 levels at melanoma diagnosis are associated with thicker primaries and poorer survival. We postulated that this might relate to the deleterious effect of systemic inflammation as 25-hydroxyvitamin D2 /D3 levels are inversely associated with levels of C-reactive protein. 2,182 participants in the Leeds Melanoma Cohort (median follow-up 7.98 years) provided data on drug exposure, comorbidities and a serum 25-hydroxyvitamin D2 /D3 level at recruitment. Factors reported to modify systemic inflammation (low vitamin D levels, high body mass index, use of aspirin or nonsteroidal anti-inflammatory drugs or smoking were tested as predictors of microscopic ulceration (in which primary tumors are inflamed) and melanoma-specific survival (MSS). Ulceration was independently associated with lower 25-hydroxyvitamin D2 /D3 levels (odds ratio (OR) = 0.94 per 10 nmol/L, 95% CI 0.88-1.00, p = 0.05) and smoking at diagnosis (OR = 1.47, 95% CI 1.00-2.15, p = 0.04). In analyses adjusted for age and sex, a protective effect was seen of 25-hydroxyvitamin D2 /D3 levels at diagnosis on melanoma death (OR = 0.89 per 10 nmol/L, 95% CI 0.83-0.95, p < 0.001) and smoking increased the risk of death (OR = 1.13 per 10 years, 95% CI 1.05-1.22, p = 0.001). In multivariable analyses (adjusted for tumor thickness) the associations with death from melanoma were low 25-hydroxyvitamin D2 /D3 level at recruitment (<20 nmol/L vs. 20-60 nmol/L, hazard ratio (HR) = 1.52, 95% CI 0.97-2.40, p = 0.07) and smoking duration at diagnosis (HR = 1.11, 95% CI 1.03-1.20, p = 0.009). The study shows evidence that lower vitamin D levels and smoking are associated with ulceration of primary melanomas and poorer MSS. Further analyses are necessary to understand any biological mechanisms that underlie these findings. | Matsumoto Y, Sugioka Y, Tada M, Okano T, Mamoto K, Inui K, Habu D, Koike T (2015)
Relationships between serum 25-hydroxycalciferol, vitamin D intake and disease activity in patients with rheumatoid arthritis--TOMORROW study.
Modern rheumatology 25, 246-250 [PubMed:25211403]
[show Abstract]
ObjectivesThe effect of serum 25-hydroxycalciferol [25(OH)D] on rheumatoid arthritis (RA) activity remains controversial. This study was undertaken with an aim to clarify the relationship between serum 25(OH)D and RA activity, and to determine the effects of dietary vitamin D intake and age on serum 25(OH)D level.MethodsA total of 208 outpatients with RA were matched according to age and sex with 205 individuals without RA (controls) from the TOMORROW study (UMIN000003876). We excluded 27 patients with RA and 19 control subjects who had been prescribed vitamin D medication or were taking vitamin D supplements. Vitamin D intake was assessed in the remaining 181 patients and 186 controls using the brief-type dietary history questionnaire. Serum 25(OH)D levels were measured using a radioimmunoassay.ResultsSerum 25(OH)D levels were significantly lower in patients with RA than in the controls (p < 0.001). There was a significant and positive correlation between age and 25(OH)D in the patients (r = 0.283, p < 0.001), as with vitamin D intake and 25(OH)D, even after adjusting for age (r = 0.313, p < 0.001). Disease activity and 25(OH)D did not significantly correlate.ConclusionsPatients with RA were observed to have serum 25(OH)D levels which correlated with vitamin D intake and age but not disease activity. | van den Ouweland JM, Beijers AM, van Daal H (2014)
Overestimation of 25-hydroxyvitamin D3 by increased ionisation efficiency of 3-epi-25-hydroxyvitamin D3 in LC-MS/MS methods not separating both metabolites as determined by an LC-MS/MS method for separate quantification of 25-hydroxyvitamin D3, 3-epi-25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human serum.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 967, 195-202 [PubMed:25125396]
[show Abstract]
BackgroundAn LC-MS/MS method was developed for simultaneous quantification of 25-hydroxyvitamin D3 (25(OH)D3), 3-epi-25(OH)D3, and 25(OH)D2 in human serum.MethodsSample preparation consisted of protein precipitation followed by off-line SPE. Calibration curves for each vitamin D metabolite were constructed in phosphate-buffered saline with 60 g/L albumin including its corresponding stable isotope labelled (SIL) internal standard. A pentafluorophenyl (PFP) analytical column was used to resolve 25(OH)D3 from 25(OH)D2 and 3-epi-25(OH)D3, followed by SRM registration using positive ESI-MS/MS. Accuracy was assessed from measurement of samples with NIST reference method procedure (RMP) assigned values. The PFP LC-MS/MS method was compared to an in-house C18 column LC-MS/MS method, not resolving 25(OH)D3 from 3-epi-25(OH)D3, using adult and newborn samples.ResultsIntra-assay and inter-assay coefficients of variation were less than 4% and 7.5%, respectively for all three vitamin D metabolites; lower limits of quantification were 1, 1 and 2 nmol/L and linearity of methods were 1-500, 1-200 and 2-500 nmol/L for 25(OH)D3, 3-epi-25(OH)D3 and 25(OH)D2, respectively. The PFP LC-MS/MS method showed minimal bias to the NIST RMP. Method comparison revealed that in the C18 LC-MS/MS method, the 3-epi-25(OH)D3 concentration is overestimated inadvertently not only from co-elution of both analytes, but also by an additional 30-40% higher ionisation efficiency of 3-epi-25(OH)D3 when compared to 25(OH)D3.ConclusionThis accurate LC-MS/MS method allows the simultaneous measurement of 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 in human serum. Due to increased ionisation efficiency, the contribution of the 3-epi-25(OH)D3 metabolite to the total 25(OH)D3 concentration is significantly overestimated in MS methods that do not resolve 3-epi-25(OH)D3 from 25(OH)D3 and may compromise its use in infant samples known to have significant amounts of 3-epi-25(OH)D3. | Shinkyo R, Sakaki T, Kamakura M, Ohta M, Inouye K (2004)
Metabolism of vitamin D by human microsomal CYP2R1.
Biochemical and biophysical research communications 324, 451-457 (Source: SUBMITTER) [PubMed:15465040]
[show Abstract]
The activation of vitamin D requires 25-hydroxylation in the liver and 1alpha-hydroxylation in the kidney. However, it remains unclear which enzyme is relevant to vitamin D 25-hydroxylation. Recently, human CYP2R1 has been reported to be a potential candidate for a hepatic vitamin D 25-hydroxylase. Thus, vitamin D metabolism by CYP2R1 was compared with human mitochondrial CYP27A1, which used to be considered a physiologically important vitamin D(3) 25-hydroxylase. A clear difference was observed between CYP2R1 and CYP27A1 in the metabolism of vitamin D(2). CYP2R1 hydroxylated vitamin D(2) at the C-25 position while CYP27A1 hydroxylated it at positions C-24 and C-27. The K(m) and k(cat) values for the CYP2R1-dependent 25-hydroxylation activity toward vitamin D(3) were 0.45microM and 0.97min(-1), respectively. The k(cat)/K(m) value of CYP2R1 was 26-fold higher than that of CYP27A1. These results strongly suggest that CYP2R1 plays a physiologically important role in the vitamin D 25-hydroxylation in humans. |
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