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1.
N Ohnuma K Bannai H Yamaguchi Y Hashimoto A W Norman 《Archives of biochemistry and biophysics》1980,204(1):387-391
A new vitamin D metabolite was isolated in pure form from the blood of rats given oral doses of 50 μg/kg of 1α-hydroxyvitamin D3. The isolation involved methanol-chloroform extraction and four successive column chromatographic procedures. A tentative structure of the metabolite is proposed on the basis of its column chromatographic behavior via mass spectrometry, ultraviolet absorption spectrophotometry, and as 1α,3β,25-trihydroxy-9,10 (19)-cholestatrieno-26,23-lactone. The trivial name 1α,25-dihydroxyvitamin D3-26,23-lactone is suggested for this compound. 相似文献
2.
A new vitamin D3 metabolite was isolated in pure form (18.2 micrograms) from the serum of rats given large doses (two doses of 26 mumol/rat) of vitamin D3. The new metabolite has been unequivocally identified as 3 beta, 25-dihydroxy-9,10-seco-5,7,10(19)-cholestatrieno-26,23-peroxylactone by ultraviolet absorption spectrophotometry, Fourier transform infrared spectrophotometry, mass spectrometry, field desorption mass spectrometry, and specific chemical reaction with triphenyl phosphine. The stereochemical configuration at the C-23 and c-25 positions of the 25-hydroxyvitamin D3-26-23-peroxylactone was definitely determined to be the 23(S)25(R),25-hydroxyvitamin D3-26,23-peroxylactone is suggested for this metabolite. The isolation involved chloroform-methanol extraction and four column chromatographic procedures. The metabolite purification and elution position on these columns were followed by UV measurement at 264 nm. This metabolite was ultimately resolved from the previously known 25-hydroxyvitamin D3-26,23-lactone by high pressure liquid chromatography using a Zorbax Sil column. The 25-hydroxyvitamin D3-26,23-peroxylactone was converted upon storage at room temperature or -20 degrees C into the 25-hydroxyvitamin D3-26,23-lactone. Since under the conditions of this isolation only the 26,23-peroxylactone and no 26,23-lactone of 25-hydroxyvitamin D3 was present in the rat serum, this suggests that the 25-hydroxyvitamin D3-26,23-peroxylactone is the naturally occurring metabolite. 相似文献
3.
R L Horst 《Biochemical and biophysical research communications》1979,89(1):286-293
A new metabolite of Vitamin D3 (25-OHD3-26,23-lactone) has been found in the plasma of Vitamin D3-toxic pigs and cows. This metabolite is at least 5 times more potent than 25-OHD3 in the displacement of [3H]-25-OHD3 from rat plasma protein binding sites under short-term incubation. This metabolite co-migrates with 24,25-(OH)2D3 on Sephadex LH-20 columns developed in chloroform:hexane 65:35 and with 25,26-(OH)2D3 on Sephadex LH-20 columns developed in hexane:chloroform:methanol 9:1:1. The presence of 25-OHD3-26,23-lactone represents a possible contaiminant in the assay of 24,25-(OH)2D3 or 25,26-(OH)2D3 if only Sephadex LH-20 is used for pre-assay purification. 25-OHD3-26,23-lactone is, however, resolved from 24,25-(OH)2D3 by high pressure liquid chromatography (HPLC) using Zorbax Sil silicic acid columns developed in either isopropanol:hexane 8:92 or isopropanol:methylene chloride 2.5:96.5. We assayed for the presence of this new metabolite of Vitamin D3 and found it to be present in normal pig plasma and undetectable in normal cow plasma. Concentrations were elevated to 10–20 ng/ml following massive injection of Vitamin D3 to both species. 相似文献
4.
25,26-dihydroxyvitamin D3 is not a major intermediate in 25-hydroxyvitamin D3-26,23-lactone formation 总被引:1,自引:0,他引:1
Structural similarities between 25S,26-dihydroxyvitamin D3 and 25-hydroxyvitamin D3-26,23-lactone and their concomitant multifold increase in the plasma of animals treated with pharmacological doses of vitamin D3 suggest a precursor-product relationship. However, a single dose of 25S,26-[3H]dihydroxyvitamin D3 given to rats treated chronically with pharmacological amounts of vitamin D3 did not result in detectable plasma 25-[3H]hydroxyvitamin D3-26,23-lactone. Multiple doses of synthetic 25S,26-dihydroxyvitamin D3 given to vitamin D3-deficient rats treated chronically with pharmacological amounts of vitamin D2 also did not result in detectable plasma 25-hydroxyvitamin D3-26,23-lactone. Furthermore, homogenates prepared from vitamin d-deficient chickens, dosed with 1,25-dihydroxyvitamin D3, converted 25-[3H]hydroxyvitamin D3 to 25-[3H]hydroxyvitamin D3-26,23-lactone. But these same homogenates did not convert 25S,26-[3H]dihydroxyvitamin D3 to 25-[3H]hydroxyvitamin D3-26,23-lactone. These data indicate that 25,26-dihydroxyvitamin D3 is not an intermediate in 25-hydroxyvitamin D326, 23-lactone formation. 相似文献
5.
T A Reinhardt J L Napoli D C Beitz E T Littledike R L Horst 《Biochemical and biophysical research communications》1981,99(1):302-307
The enzymatic conversion of 5-methylthioribose to methionine and its deaminated derivatives, 2-keto-4-methylmercaptobutyric acid and 2-hydroxy-4-methylmercaptobutyric acid by cell-free extracts of has been demonstrated. 14C-Labeled methionine was isolated from incubation mixtures with 5-methylthio[U-14C]ribose. The carbohydrate part of this compound furnishes at least part, if not all, of the four carbon chain of methionine. 相似文献
6.
Yan-Ru Lou Ferdinand Molnár Mikael Peräkylä Shengjun Qiao Allan V. Kalueff René St-Arnaud Carsten Carlberg Pentti Tuohimaa 《The Journal of steroid biochemistry and molecular biology》2010,118(3):162-170
25-Hydroxyvitamin D3 1α-hydroxylase encoded by CYP27B1 converts 25-hydroxyvitamin D3 into 1α,25-dihydroxyvitamin D3, a vitamin D receptor ligand. 25-Hydroxyvitamin D3 has been regarded as a prohormone. Using Cyp27b1 knockout cells and a 1α-hydroxylase-specific inhibitor we provide in four cellular systems, primary mouse kidney, skin, prostate cells and human MCF-7 breast cancer cells, evidence that 25-hydroxyvitamin D3 has direct gene regulatory properties. The high expression of megalin, involved in 25-hydroxyvitamin D3 internalisation, in Cyp27b1?/? cells explains their higher sensitivity to 25-hydroxyvitamin D3. 25-Hydroxyvitamin D3 action depends on the vitamin D receptor signalling supported by the unresponsiveness of the vitamin D receptor knockout cells. Molecular dynamics simulations show the identical binding mode for both 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 with the larger volume of the ligand-binding pocket for 25-hydroxyvitamin D3. Furthermore, we demonstrate direct anti-proliferative effects of 25-hydroxyvitamin D3 in human LNCaP prostate cancer cells. The synergistic effect of 25-hydroxyvitamin D3 with 1α,25-dihydroxyvitamin D3 in Cyp27b1?/? cells further demonstrates the agonistic action of 25-hydroxyvitamin D3 and suggests that a synergism between 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 might be physiologically important. In conclusion, 25-hydroxyvitamin D3 is an agonistic vitamin D receptor ligand with gene regulatory and anti-proliferative properties. 相似文献
7.
M Axelson 《FEBS letters》1985,191(2):171-175
25-Hydroxyvitamin D3 3 beta-sulphate has been identified in human plasma. The compound was isolated by anion-exchange chromatography and following hydrolysis it was characterized by high-performance liquid chromatography and gas chromatography-mass spectrometry. The mean concentration of sulphated 25-hydroxyvitamin D3 in plasma from 60 patients was 16.7 +/- 7.1 ng/ml and the levels often exceeded those of the corresponding free compound. The study also shows that unconjugated 25-hydroxyvitamin D3 is not readily sulphated by man in vivo. 相似文献
8.
1 alpha,25-Dihydroxyvitamin D3-26,23-lactone [1 alpha,25(OH)2D3-26,23-lactone] was compared to 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] in terms of their stimulation, in vivo, of intestinal calcium transport and mobilization of calcium from bone in the rat (the two classic vitamin D-mediated responses), and their relative binding to the chick intestinal receptor for 1 alpha,25(OH)2D3, 1 alpha,25-(OH)2D3-26,23-lactone was found to be only one-thirtieth as active as 1 alpha,25-(OH)2D3 in the stimulation of intestinal calcium transport and was found to mediate a significant reduction in the steady-state serum calcium levels. Associated with the reduction in serum calcium was a significant increase in urinary calcium excretion for 24 h after the administration of the steroid. Prior administration of 1 alpha,25(OH)2D3-26,23-lactone partially blocked the actions of a subsequently administered dose of 1 alpha,25(OH)2D3 in increasing serum calcium levels, but did not affect the action of 1 alpha,25(OH)2D3 in stimulating intestinal calcium transport. The binding affinity of 1 alpha,25(OH)2D3-26,23-lactone to the chick intestinal cytosol receptor protein was observed to be 670 times lower than that of 1,25-(OH)2D3 which indicates that perturbation of the 25-hydroxylated side chain by formation of the 26,23-lactone causes a significant reduction in ligand affinity for the receptor. 相似文献
9.
Four possible diastereoisomers of 1 alpha,25-dihydroxyvitamin D3-26,23-lactone were chemically synthesized and compared with the natural metabolite by high-pressure liquid chromatography. The four synthetic diastereoisomers of 1 alpha,25-dihydroxyvitamin D3-26,23-lactone could be separated into three peaks by high-pressure liquid chromatography. The naturally occurring 1 alpha,25-dihydroxyvitamin D3-26,23-lactone isolated from dog serum and in vitro incubation of chick kidney homogenates comigrated with 23(S)25(R)-1 alpha,25-dihydroxyvitamin D3-26,23-lactone. The four diastereoisomers of 1 alpha,25-dihydroxyvitamin D3-26,23-lactone were tested against naturally occurring 1 alpha,25-dihydroxyvitamin D3-26,23-lactone to determine their relative competition in the 1 alpha,25-dihydroxyvitamin D3-specific cytosol receptor binding assay for 1 alpha,25-dihydroxyvitamin D3. 23(S)25(S)-1 alpha,25-Dihydroxyvitamin D3-26,23-lactone was the best competitor followed by 23(R)25(R)-1 alpha,25-dihydroxyvitamin D3-26,23-lactone and 23(R)25(S)-1 alpha,25-dihydroxyvitamin D3-26,23-lactone, and 23(S)25(R)-1 alpha,25-dihydroxyvitamin D3-26,23-lactone was the poorest competitor. Natural 1 alpha,25-dihydroxyvitamin D3-26,23-lactone isolated from dog serum had almost the same binding affinity as that of 23(S)25(R)-1 alpha,25-dihydroxyvitamin D3-26,23-lactone. These data unequivocally demonstrate that the stereochemistry of the natural 1 alpha,25-dihydroxyvitamin D3-26,23-lactone has the 23(S) and 25(R) configuration. 相似文献
10.
R.L. Horst B.C. Pramanik T.A. Reinhardt S.-J. Shiuey J.J. Partridge M.R. Uskokovic J.L. Napoli 《Biochemical and biophysical research communications》1982,106(3):1006-1011
23,25-Dihydroxyvitamin D3 was isolated from the plasma of vitamin D3-toxic pigs. An ultraviolet absorbance spectrum confirmed its purity. The configuration of the 23-hydroxyl group was determined to be S by comparison of the natural product with synthetic 23,25- and 23,25-dihydroxyvitamin D3 by high-pressure liquid chromatography. The affinity of both 23,25- and 23,25-dihydroxyvitamin D3 for the plasma vitamin D binding protein was similar to vitamin D3. Thus, with respect to the plasma vitamin D binding protein, 23,25-dihydroxyvitamin D3 is the least potent, naturally-occurring, dihydroxylated vitamin D3 metabolite known. 相似文献
11.
23, 25, 26-trihydroxycholecalciferol. A 25-hydroxycholecalciferol-26,23-lactone precursor. 总被引:1,自引:1,他引:0
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(23S)-23,25-Dihydroxycholecalciferol was converted into at least five metabolites in kidney homogenates prepared from 1,25-dihydroxycholecalciferol-treated chickens. One of these has been positively identified as 23,25,26-trihydroxycholecalciferol by u.v.-absorbance analysis, mass spectrometry and chemical formation of derivatives. 23,25,26-Trihydroxycholecaciferol produces 25-hydroxycholecalciferol-26,23-lactone when incubated in chick kidney homogenates. 相似文献
12.
The present study was carried out in order to elucidate the metabolic pathway from 1 alpha,25-(OH)2D3 to 1 alpha,25-(OH)2D3-26,23-lactone. For that purpose, we stereospecifically synthesized the vitamin D3 derivatives 1 alpha,23(S),25-(OH)3D3, 1 alpha,23(S),25(R),26-tetrahydroxyvitamin D3, and 23(S),25(R)-1 alpha,25-dihydroxyvitamin D3-lactol. The in vitro metabolism of these compounds was examined in kidney homogenates and intestinal mucosa homogenates from 1 alpha,25-(OH)2D3-supplemented chicks. The naturally occurring 23(S),25(R)-1 alpha,25-dihydroxyvitamin D3-26,23-lactone was produced (in increasing amounts) from 1 alpha,25-(OH)2D3, 1 alpha,25(R),26-(OH)3D3, 1 alpha,23(S),25-(OH),D3, 1 alpha,23(S),25(R),26-(OH)4D3, and 23(S),25(R)-1 alpha,25-(OH)2D3-26,23-lactol. These results indicated that there are two possible metabolic pathways from 1 alpha,25-(OH)2D3 to 1 alpha,23(S),25(R),26-(OH)4D3: the major one is by way of 1 alpha,23(S),25-(OH)3D3 and the minor one is by way of 1 alpha,25(R),26-(OH)3D3. 1 alpha,23(S),25(R),26-Tetrahydroxyvitamin D3 is further metabolized to 23(S),25(R)-1 alpha,25-dihydroxyvitamin D3-26,23-lactone via 23(S),25(R)-1 alpha,25-dihydroxyvitamin D3-26,23-lactol. In the course of our studies, a new biosynthetic vitamin D3 metabolite was isolated in pure form. This metabolite was identified as 23(S),25(R)-1 alpha,25-(OH)2D3-26,23-lactol by UV spectrophotometry and mass spectrometry. Furthermore, we establish in this report that the lactonization of 1 alpha,23,25,26-(OH)4D3 and 1 alpha,25-(OH)2D3-26,23-lactol occurs in a stereo-retained and stereo-selective fashion. 相似文献
13.
14.
T H Nahm S W Lee A Fausto Y Sonn L V Avioli 《Biochemical and biophysical research communications》1979,89(2):396-402
Serum and hepatic 25-hydroxyvitamin D (25OHD), and serum calcium, phosphate, 25OHD3 binding capacity and binding affinity were measured in male and female trout. Both serum and hepatic 25OHD levels are decreased in female trout with elevations in protein bound calcium and phosphate. Whereas the apparent dissociation constant (Kd) for serum binding of 25OHD3 of 1.0–2.0 × 10?9M is similar in males and females, the 25OHD3 binding capacity of hypercalcemic spawning trout (1.39 × 10?7M) is significantly less than that of male fish (1.88 × 10?7M). At circulating serum concentrations of 25OHD which average 9.5 × 10?9M only 5–7% of trout serum 25OHD binding sites are occupied. 相似文献
15.
A new chromatographic system for vitamin D3 and its metabolites: resoluation of a new vitamin D3 metabolite 总被引:25,自引:0,他引:25
A simple yet powerful new chromatographic procedure for vitamin D(3) and its metabolites is described. Liquid-gel partition chromatography on Sephadex LH-20 using a solvent of various percentages of CHCl(3) in Skellysolve B (petroleum ether, bp 67-69 degrees C) permits excellent resolution of vitamin D(3), 25-hydroxyvitamin D(3), and their more polar metabolites. Of special importance is the resolution of the metabolites of vitamin D(3) more polar than 25-hydroxycholecalciferol. Because of this resolution, a new metabolite of vitamin D(3) has been demonstrated in the plasma of rats and in the intestines of chicks given 100 IU of vitamin D(3)-1,2-(3)H. 相似文献
16.
Three new in vivo metabolites of 1 alpha,25-dihydroxyvitamin D3 were isolated from the serum of dogs given large doses (two doses of 1.5 mg/dog) of 1 alpha,25-dihydroxyvitamin D3. The metabolites were isolated and purified by methanol-chloroform extraction and a series of chromatographic procedures. By cochromatography on a high-performance liquid chromatograph, ultraviolet absorption spectrophotometry, mass spectrometry, Fourier-transform infrared spectrophotometry, and specific chemical reactions, the metabolites were identified as 1 alpha,25-dihydroxy-24- oxovitamin D3, 1 alpha,25-dihydroxyvitamin D3 26,23-lactone, and 1 alpha,24(S),25-trihydroxyvitamin D3. According to these procedures, the total amounts of the isolated metabolites were as follows: 1 alpha,25-dihydroxyvitamin D3, 23.6 micrograms; 1 alpha,25-dihydroxy-24- oxovitamin D3, 1.8 micrograms; 1 alpha,25-dihydroxyvitamin D3 26,23-lactone, 9.2 micrograms; 1 alpha,24(R),25-trihydroxyvitamin D3, 15.4 micrograms; 1 alpha,24(S),25-trihydroxyvitamin D3, 1.0 microgram. With recovery corrections, the serum levels of each metabolite were approximately 49 ng/mL for 1 alpha,25-dihydroxyvitamin D3, 3.7 ng/mL for 1 alpha,25-dihydroxy-24- oxovitamin D3, 19 ng/mL for 1 alpha,25-dihydroxyvitamin D3 26,23-lactone, 32 ng/mL for 1 alpha,24(R),25-trihydroxyvitamin D3, and 2.1 ng/mL for 1 alpha,24(S),25-trihydroxyvitamin D3. 相似文献
17.
18.
mRNA was prepared from autopsy liver samples from a homozygote for α1-antitrypsin deficiency (PiZZ) and from a normal (PiMM) subject. Both preparation gave equivalent synthesis of α1-antitrypsin in a wheat germ cell-free system. This suggests that the deficiency of plasma α1-antitrypsin associated with the Z variant is due to a failure of processing and secretion of the protein rather than of its synthesis. It is likely that it is the resultant intracellular accumulation of the Z protein rather than a deficiency of protease inhibitor that is the primary cause of the liver pathology associated with this variant. 相似文献
19.
S B Arnaud R S Goldsmith P W Lambert V L Go 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1975,149(2):570-572
Within 24 hr after intravenous administration of isotopic 25-hydroxyvitamin D3 to three normal adults for kinetic studies, one-third of the radioactivity was secreted into the lumen of the duodenum, probably with the bile. The subsequent intestinal reabsorption of over 85% of secreted radioactivity suggests that this major metabolite of vitamin D has a hitherto unrecognized enterohepatic circulation. Our observation of a dynamic hepatic secretion and intestinal reabsorption of radioactivity administered as 3H-labeled 25-hydroxyvitamin D3 to vitamin D-replete man is indicative of an enterohepatic circulation that may be of physiologic importance. It is conceivable that interruption in the recycling of 25-OH-D3 may be an important mechanism of acquired deficiency of vitamin D in gastrointestinal disease. 相似文献