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H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 523 records · Page 29Linked to original sources
PubMed1977

Mechanism of 25-hydroxyvitamin D3 24-hydroxylation: incorporation of oxygen-18 into the 24 position of 25-hydroxyvitamin D3.

The oxygen enzymatically inserted as a hydroxyl function by chick kidney homogenate into the 24 position of 25-hydroxyvitamin D3 to give 24,25-dihydroxyvitamin D3 is derived exclusively from 18O2. Therefore, like the 25-hydroxyvitamin D3-lalpha-hydroxylase system, the 25-hydroxyvitamin D3-24-hydroxylase system is also a monooxygenase ("mixed-function oxidase").

Animals↗
PubMed1977

Adequate response of plasma 1,25-dihydroxyvitamin D to parturition in paretic (milk fever) dairy cows.

The concentration of 1,25-dihydroxyvitamin D was measured by means of a radioactive receptor assay in the plasma of cows during the period immediately prior to, during, and following parturition. Nonparetic cows showed initially a slight decrease in plasma 1,25-dihydroxyvitamin D which was followed by a significant increase during parturition and 2 days postpartum. The highest concentration achieved in the control or nonparetic cows was 100 picograms per milliliter. In the paretic animals the plasma 1,25-dihydroxyvitamin D concentration increased sharply during the day preceding calving and reached a maximum of 200 picograms per milliliter at parturition. This level was maintained during the ensuing 2.5 days. These results demonstrate that parturient paresis cannot be the result of insufficient synthesis or secretion of 1,25-dihydroxyvitamin D.

Animals↗
PubMed1977

Solanum glaucophyllum as source of 1,25-dihydroxyvitamin D3.

Vitamin D-deficient rats given an aqueous extract of the South American plant Solanum glaucophyllum accumulate 1,25-dihydroxyvitamin D3 in their blood and intestines at the time they show enhanced intestinal calcium absorption. The identity of the 1,25-dihydroxyvitamin D3 was established by co-chromatography with 1,25-dihydroxy[23,24-3H]vitamin D3 on Sephadex LH-20 columns, microparticulate silica gel columns, a reversed-phase column developed under high pressure, and by a specific 1,25-dihydroxyvitamin D3 binding assay. The chromatographic systems used are fully capable of resolving all of the known metabolites of vitamin D3. Serum of the S. glaucophyllum-treated rats showed 300 pg/ml of 1,25-dihydroxyvitamin D3 and no detectable 1,25-dihydroxyvitamin D2. Similarly, intestine of such rats had 230 pg/g of 1,25-dihydroxyvitamin D3. Control animals which received the vehicle instead of S. glaucophyllum had only 20 pg/ml of 1,25-dihydroxyvitamin D3 in their serum and 4.4 pg/g of 1,25-dihydroxyvitamin D2 in their intestine. These results demonstrate that S. glaucophyllum extracts must be a source of 1,25-dihydroxyvitamin D3; thus a significant basis for the calcinogenic properties of S. glaucophyllum must be the presence of a conjugated form of 1,25-dihydroxyvitamin D3, which is rendered available by digestion.

Animals↗
PubMed1977

The 24-hydroxylation of 1,25-dihydroxyvitamin D3.

The production of 1,24,25-trihydroxyvitamin D3 in vivo in vitamin D-deficient rats has been demonstrated from either 25-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3. The stereochemical configuration of the hydroxyl on the 24 position of 1,24,25-trihydroxyvitamin D3 has also been unambiguously established to be R. Nephrectomy failed to eliminate the conversion of 1,25-dihydroxyvitamin D3 to the 1,24,25-trihydroxyvitamin D3, establishing that the 24-hydroxylase can be demonstrated in at least one organ in addition to kidney in contrast to the 1-hydroxylase. 1,24,25-Trihydroxyvitamin D3 can also be produced in vivo from 1alpha-hydroxyvitamin D3 or from 24-hydroxyvitamin D3, analogs of vitamin D3 which are not naturally occurring. Using chick kidney mitochondrial preparations it has been demonstrated that the 24-hydroxylase is able to utilize 1,25-dihydroxyvitamin D3 as a substrate whereas it is unable to utilize 1alpha-hydroxyvitamin D3. In addition, the chicke kidney 1-hydroxylase is known to convert 24,25-dihydroxyvitamin D3 to the 1,24,25-trihydroxyvitamin D3, but this hydroxylase is unable to act on the 24-hydroxyvitamin D3. These results demonstrate that the renal vitamin D hydroxylases require that a hydroxyl be on the 25 carbon of the vitamin D molecule before it can be 1- or 24-hydroxylated.

Animals↗
PubMed1977

Synthesis of 1alpha-hydroxyergocalciferol.

A synthesis of 1alpha-hydroxyergocalciferol (1alpha-hydroxyvitamin D2, a potent analog of vitamin D2, is described. The preparation route involves conversion of ergosterol in two steps (60%) to the known ergosta-4, 6, 22-trien-3-one and dehydrogenation of the triene with SeO2 to ergosta-1,4,6,22-tetraen-3-one (30%). Epoxidation of the tetraenone to the corresponding 1alpha, 2alpha-epoxide followed by Li/NH3 reduction gave ergosta-5,22-diene-1alpha, 3beta-diol in 26% yield from the tetranone. After conversion to the corresponding diacetate and allylic bromination/dehydrobromination 1alpha-acetoxyergosteryl acetate was obtained. Irradiation of this intermediate gave the previtamin which was converted to the new vitamin analog by thermal equilibration and hydrolysis of the acetates. Charcteristic uv, nmr and mass spectral patterns confirmed the structure of the product.

Ergocalciferols↗
PubMed1977

Intestinal 1,25-dihydroxyvitamin D3 binding protein: specificity of binding.

The binding of metabolites of vitamin D and their analogs to the 3.7S chick intestinal cytosol receptor protein has been specifically studied by competitive binding techniques and polyethylene glycol precipitation of the complex. The structural requirements for the interaction between the vitamin D molecule and the receptor could be assessed without the nuclear chromatin binding step. These measurements have shown that 1,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D2 are equally competitive and are the most active. Of the structural features of the compounds, the 1 alpha-hydroxyl is most important followed by the 25-hydroxyl and the 3 beta-hydroxyl. The addition of a second hydroxyl near carbon 25 markedly reduces binding whether on the 26 carbon or the 24 carbon. A hydroxyl on C-24 could substitute to some degree for the 25-hydroxyl inasmuch as 24-hydroxyvitamin D3 was much more effective than vitamin D3 but less effective than 25-hydroxyvitamin D3. In general the patterns of binding affinities correlated well with the biological activity of the various analogs strongly supporting a physiological role for the 1,25-dihydroxyvitamin D3 binding protein. It also suggests that of the two-step receptor mechanism, the structural specificity is located in the initial interaction of the 1,25-dihydroxyvitamin D3 and the cytosol receptor.

Animals↗
PubMed1977

Effectiveness of 1 alpha-hydroxyvitamin D3 in children with renal osteodystrophy associated with hemodialysis.

Two children who were receiving maintenance hemodialysis were treated with 1 to 4 microng/day of 1 alpha-hydroxyvitamin D3 for 500 to 700 days, respectively. Sequential parathyroid hormone levels and radiologic evaluations showed considerable improvement in one patient. The second patient initially responded with healing of the bone disease. Subsequent deterioration may be related either to medical noncomplicance and/or interference by diphenylhydantoin in the subsequent hepatic 25-hydroxylation of 1 alpha-OH-D3.

Adolescent↗
PubMed1977

Mediation of calcium adaptation by 1,25-dihydroxycholecalciferol.

Vitamin D-depleted chicks which were repleted with 25-hydroxycholecalciferol adapted to the feeding of a low or high calcium diet by respectively increasing or decreasing their rate of intestinal calcium absorption. The synthesis of 1,25-dihydroxycholecalciferol in chicks fed differing calcium diets correlated directly with intestinal calcium absorption activity, suggesting that the intestinal calcium adaptation response is mediated by the modulation of kidney 25-hydroxycholecalciferol-1-hydroxylase activity. This view was strongly supported by the demonstration that repletion of the chicks with 1,25-dihydroxycholecalciferol eliminated the ability of the chicks to adjust their rates of intestinal calcium absorption to dietary levels of calcium.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1977

Lack of effect of calcitonin on the regulation of vitamin D metabolism in the rat.

The infusion of calcitonin into intact rats increases the accumulation of 1,25-dihydroxy-[26-27-3H]vitamin D3 from 25-hydroxy-[26,27,-3H]vitamin D3 in blood, but has no effect on thyroparathyroidectomized rats using a variety of protocols. Furthermore, the vitamin D status of the animals did not alter the results. Inasmuch as no effect of calcitonin could be found on the accumulation of other vitamin D metabolites as well as 1,25-dihydroxyvitamin D3, it is concluded that calcitonin apparently plays no direct role in the regulation of vitamin D metabolism and that the previous report of an effect of calcitonin on vitamin D metabolism in vivo is probably the result of a secondary response of the parathyroid gland.

Animals↗
PubMed1977

Lack of effect of vitamin D and its metabolites on intestinal phosphate transport in familial hypophosphatemia of mice.

Intestinal calcium and phosphate transport was studied in normal and hypophosphatemic mice fed a variety of dietary regimens with and without vitamin D. Regardless of dietary phosphorus levels, the genetic hypophosphatemic mice had drastically reduced levels of serum inorganic phosphate and intestinal phosphate transport while showing only slightly reduced serum calcium and intestinal calcium transport levels. The inclusion of vitamin D in the diet did not increase the low serum phosphorus levels and low rates of intestinal phosphate transport in the genetic hypophosphatemic mice, while it did increase serum calcium and intestinal calcium transport levels. The administration of 1,25-dihydroxyvitamin D3 to the hypophosphatemic mice stimulated intestinal calcium transport but had no effect on intestinal phosphate transport. In contrast, the 1,25-dihydroxyvitamin D3 stimulated both phosphate and calcium transport in the intestine of normal mice. The results obtained are consistent with the hypothesis that the primary metabolic disturbance in familial hypophosphatemia involves a defect in phosphate transport mechanisms.

Animals↗