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1.
Intestinal synthesis of 24-keto-1,25-dihydroxyvitamin D3. A metabolite formed in vivo with high affinity for the vitamin D cytosolic receptor 总被引:1,自引:0,他引:1
J L Napoli B C Pramanik P M Royal T A Reinhardt R L Horst 《The Journal of biological chemistry》1983,258(15):9100-9107
24-Keto-1,25-dihydroxyvitamin D3 has been identified as an intestinal metabolite of 1,25-dihydroxyvitamin D3 by ultraviolet absorbance, mass spectroscopy, and chemical reactivity. The metabolite was produced from 1,25-dihydroxyvitamin D3 and 1,24R,25-trihydroxyvitamin D3 in rat intestinal mucosa homogenates. 24-Keto-1,25-dihydroxyvitamin D3 is present in vivo in the plasma and small intestinal mucosa of rats fed a stock diet, receiving no exogenous 1,25-dihydroxyvitamin D3, and in the plasma and small intestinal mucosa of rats dosed chronically with 1,25-dihydroxyvitamin D3. 24-Keto-1,25-dihydroxyvitamin D3 has affinity equivalent to 1,24R,25-trihydroxyvitamin D3 for the 3.7 S cytosolic receptor specific for 1,25-dihydroxyvitamin D3 in the intestine and thymus. In cytosolic preparations contaminated with the 5 S vitamin D-binding protein, both metabolites are about 7-fold less potent than 1,25-dihydroxyvitamin D3. In contrast, in cytosolic preparations largely free of the 5 S binding protein, both metabolites are equipotent with the parent compound. No evidence was obtained supporting a substantial presence of 23-keto-1,25-dihydroxyvitamin D3 in vivo; nor was the latter compound generated in detectable amounts from 1,25-dihydroxyvitamin D3 by intestinal homogenates. Thus, C-24 oxidation is a significant pathway of intestinal 1,25-dihydroxyvitamin D3 metabolism that produces metabolites with high affinity for the cytosolic receptor which mediates vitamin D action. 相似文献
2.
Retinoic acid synthesis by cytosol from the alcohol dehydrogenase negative deermouse 总被引:3,自引:0,他引:3
Cytosolic alcohol dehydrogenase in the deermouse is coded by a single genetic locus and a strain of the deermouse which is alcohol dehydrogenase negative exists. These two strains of the deermouse were used to extend insight into the role of cytosolic alcohol dehydrogenases in the conversion of retinol into retinoic acid. Retinoic acid synthesis from physiological concentrations of retinol (7.5 microM) with cytosol from the alcohol dehydrogenase negative deermouse was 13% (liver), 14% (kidney), 60% (testes), 78% (lung), and 100% (small intestinal mucosa) of that observed with cytosol from the positive deermouse. The rates in the negative strain ranged from 0.3 to 0.7 nmol/h/mg protein: sufficient to fulfill cellular needs for retinoic acid. Ten millimolar 4-methylpyrazole inhibited retinoic acid synthesis 92, 94, 26, and 30% in kidney, liver, lung, and testes of the positive deermouse, respectively, but only 50, 30, 0, and 0% in the same tissues from the negative deermouse. Ethanol (300 mM) did not inhibit retinoic acid synthesis in kidney cytosol from the negative strain. Therefore multiple cytosolic dehydrogenases, including alcohol dehydrogenases, contribute to retinol metabolism in vitro. The only enzyme(s) likely to be physiologically significant to retinoic acid synthesis in vivo, however, is the class of dehydrogenase, distinct from ethanol dehydrogenase, that is common to both the positive and the negative deermouse. This conclusion is supported by the data described above, the kinetics of retinoic acid synthesis and retinal reduction in kidney cytosol from the negative deermouse, and the very existence of the alcohol dehydrogenase negative deermouse. This work also shows that microsomes inhibit the cytosolic conversion of retinol into retinoic acid and that the synthesis of retinal, a retinoid that has no known function outside of the eye, does not reflect the ability or capacity of a sample to synthesize retinoic acid. 相似文献
3.
(23S)-1,23,25-Trihydroxycholecalciferol, an intestinal metabolite of 1,25-dihydroxycholecalciferol.
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(23S)-23,25-Dihydroxycholecalciferol was converted into a polar metabolite in a calciferol-deficient chick kidney homogenate. The metabolite was identified as (23S)-1,23,25-trihydroxycholecalciferol by absorbance spectroscopy and mass spectrometry, and by formation of derivatives. (23S)-1,23,25-Trihydroxycholecalciferol was also observed as a 1,25-dihydroxycholecalciferol metabolite in intestinal cells isolated from 1,25-dihydroxycholecalciferol-treated rat. The trihydroxy metabolite was 50-fold less potent than 1,25-dihydroxycholecalciferol in the chick intestinal 1,25-dihydroxycholecalciferol receptor assay. 相似文献
4.
Chalcone synthase cosuppression phenotypes in petunia flowers: comparison of sense vs. antisense constructs and single-copy vs. complex T-DNA sequences 总被引:37,自引:0,他引:37
Richard A. Jorgensen Paul D. Cluster James English Qiudeng Que Carolyn A. Napoli 《Plant molecular biology》1996,31(5):957-973
Flower pigmentation patterns were scored in 185 senseChalcone synthase (Chs) transgenotes and 85 antisenseChs transgenotes; upon first flowering, 139 (75%) of sense transgenotes were found to be phenotypically altered, as were 70 (82%) of the antisense transgenotes. The observed patterns document the range of phenotypic variations that occur, as well as confirm and extend the finding that senseChs constructs produce several types of morphologybased based flower pigmentation patterns that antisenseChs constructs do not. Long-term monitoring for epigenetic variations in one population of 44 senseChs transgenotes showed that 43 (98%) were capable of producing a cosuppression phenotype. The primary determinant of sense-specific patterns of cosuppression ofChs was found to be the repetitiveness and organization pattern of the transgene, not position effects by, or readthrough from, flanking plant DNA sequences. The degree of cosuppression observed in progeny of transgenotes carrying multiple, dispersed copies as compared to that observed with a single copy of the transgene suggests that sense cosuppression ofChs is subject to a transgene dosage effect. 相似文献
5.
6.
For several species of lepidoptera, most of the approximately 350-bp
mitochondrial control-region sequences were determined. Six of these
species are in one genus, Jalmenus; are closely related; and are believed
to have undergone recent rapid speciation. Recent speciation was supported
by the observation of low interspecific sequence divergence. Thus, no
useful phylogeny could be constructed for the genus. Despite a surprising
conservation of control-region length, there was little conservation of
primary sequences either among the three lepidopteran genera or between
lepidoptera and Drosophila. Analysis of secondary structure indicated only
one possible feature in common--inferred stem loops with higher-than-random
folding energies-- although the positions of the structures in different
species were unrelated to regions of primary sequence similarity. We
suggest that the conserved, short length of control regions is related to
the observed lack of heteroplasmy in lepidopteran mitochondrial genomes. In
addition, determination of flanking sequences for one Jalmenus species
indicated (i) only weak support for the available model of insect 12S rRNA
structure and (ii) that tRNA translocation is a frequent event in the
evolution of insect mitochondrial genomes.
相似文献
7.
MF Perutz 《Current opinion in structural biology》1996,6(6):848-858
Several dominantly inherited, late onset, neurodegenerative diseases are due to expansion of CAG repeats, leading to expansion of glutamine repeats in the affected proteins. These proteins are of very different sizes and, with one exception, show no sequence homology to known proteins or to each other; their functions are unknown. In some, the glutamine repeat starts near the N-terminus, in another near the middle and in another near the C-terminus, but regardless of these differences, no disease has been observed in individuals with fewer than 37 repeats, and absence of disease has never been found in those with more than 41 repeats. Protein constructs with more than 41 repeats are toxic to E. coli and to CHO cells in culture, and they elicit ataxia in transgenic mice. These observations argue in favour of a distinct change of structure associated with elongation beyond 37–41 glutamine repeats. The review describes experiments designed to find out what these structures might be and how they could influence the properties of the proteins of which they form part. Poly-
-glutamines form pleated sheets of β-strands held together by hydrogen bonds between their amides. Incorporation of glutamine repeats into a small protein of known structure made it associate irreversibly into oligomers. That association took place during the folding of the protein molecules and led to their becoming firmly interlocked by either strand- or domain-swapping. Thermodynamic considerations suggest that elongation of glutamine repeats beyond a certain length may lead to a phase change from random coils to hydrogen-bonded hairpins. Possible mechanisms of expansion of CAG repeats are discussed in the light of looped DNA model structures. 相似文献
8.
9.
Arachidonic acid epoxidation: epoxyeicosatrienoic acids are endogenous constituents of rat liver 总被引:2,自引:0,他引:2
J Capdevila B Pramanik J L Napoli S Manna J R Falck 《Archives of biochemistry and biophysics》1984,231(2):511-517
Epoxyeicosatrienoic acids have been isolated and purified from the livers of male rats. They were identified by gas chromatography-mass spectrometric techniques. These results expand the list of in vivo-produced eicosanoids. Their documented in vitro biological activities suggest a role for them in cell and tissue homeostasis. 相似文献
10.
G E Lester R L Horst J L Napoli 《Biochemical and biophysical research communications》1984,120(3):919-925
The results of normal mode calculations on the beta 4.4, beta 6.3, beta 5.6, and beta 7.2 structures of gramicidin A are compared with infrared and Raman spectra of crystalline native, crystalline Cs+-bound, and vesicle-bound gramicidin A. The observed frequencies and frequency splittings are in good agreement with an assignment of beta 5.6, beta 7.2, and beta 6.3 structures, respectively, to the gramicidin A molecules in the above three systems. 相似文献