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H F DeLuca

Publications and source records attributed to H F DeLuca.

733 records · Page 41Linked to original sources
PubMed1966

Biologically active metabolite of vitamin D3 from bone, liver, and blood serum.

Radioactive metabolites present in bone, blood, liver, and feces of rats given (3)H vitamin D(3) have been isolated. Of these the aqueous soluble metabolite(s) from tissue and all those isolated from feces did not cure rickets in rats, while all the others were at least partially active in this regard. One of the metabolites proved to be as active as the parent vitamin in curing rickets and was found in large amounts in liver, blood, and bone. As much as 50-80% of the radioactivity in bone was found in this metabolite after a 500 IU oral dose of (3)H vitamin D(3). With 10 IU doses of 1,2-(3)H vitamin D(3), most of the radioactivity of the organs examined was found in this metabolite fraction. This metabolite appears to be more polar than vitamin D and is not an esterified form of the vitamin nor a complex of the vitamin with tissue lipids. Its possible role as the metabolically active form of the vitamin is discussed.

Animals↗
PubMedDate not supplied

On the specificity of vitamin D compounds binding to chick pig intestinal 1,25-dihydroxyvitamin D3 receptor.

The binding activity of four vitamin D metabolites and/or analogs for the intestinal 1,25-dihydroxyvitamin D3 receptor was evaluated after incubation at 25 degrees C for 1 h or at 0-4 degrees C for 18 h. The incubation conditions, which had no effect on the binding of 1,25-dihydroxyvitamin D3, had a dramatic effect on the binding of 25-hydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 and a small but reproducible effect on 24,25-dihydroxyvitamin D3 binding to receptor. Affinities 10- to 20-fold higher were obtained for 25-hydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3, and affinities 3-fold higher were obtained for 24,25-dihydroxyvitamin D3 at the 0-4 degrees C/18-h incubation. A comparison of intestinal receptor from chick and pig with nine vitamin D compounds showed no major differences between the two species. The relative affinity of the vitamin D analogs to compete with tritiated 1,25-dihydroxyvitamin D3 for the receptor in pig nuclear extract, expressed as ratios of the molar concentration required for 50% binding of the tritiated 1,25-dihydroxyvitamin D3 compared to nonradioactive 1,25-dihydroxyvitamin D3, are as follows: 1,25-dihydroxyvitamin D3 (1) = 1,25-dihydroxyvitamin D2 = 24-homo-1,25-dihydroxyvitamin D3 greater than 1,24,25-trihydroxyvitamin D3 (4) greater than 25-hydroxyvitamin D3 (21) = 10-oxo-19-nor-25-hydroxyvitamin D3 = 1 alpha-hydroxyvitamin D3 (37) greater than 24,25-dihydroxyvitamin D2 (257) much much greater than vitamin D3 (greater than 10(6)).

Animals↗
PubMedDate not supplied

Alterations in mRNA expression of duodenal 1,25-dihydroxyvitamin D3 receptor and vitamin D-dependent calcium binding protein in aged Wistar rats.

Previously, we reported that uptake of calcium into isolated duodenal cells and duodenal brush border membrane vesicles decreased in senescence. Decreases in duodenal 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptor number and 9k vitamin D-dependent calcium binding protein (CaBP) were also observed in aged rats. In this study, we examined the steady state mRNA levels of duodenal 1,25-(OH)2D3 receptor and CaBP in both adult (6-month-old) and old (24-month-old) rats. We identified one major band of 4.4 kb for 1,25-(OH)2D3 receptor mRNA. The size of the transcript was not affected by age. The content of 1,25-(OH)2D3 receptor mRNA (normalized with poly(A)+RNA) decreased 23% in the aged rat as compared to the adult rat. The expression of CaBP was also examined. A single band of 0.6 kb was observed for CaBP mRNA. The size of CaBP mRNA was not altered with age. However, the abundance of CaBP mRNA (normalized with poly(A)+RNA) was reduced 20% in the senescent rat. Thus, the results in the present study were consistent with our previous findings that the number of 1,25-(OH)2D3 receptors and the level of CaBP declined in the aged rat. However, the precise mechanism leading to the age-related deficit in mRNA expression remains to be elucidated.

Aging↗
PubMedDate not supplied

Systematic studies on synthesis, structural elucidation, and biological evaluation of A-ring diastereomers of 2-methyl-1alpha,25-dihydroxyvitamin D(3) and 20-epi-2-methyl-1alpha,25-dihydroxyvitamin D(3).

All possible A-ring diastereomers of 2-methyl-1alpha,25-dihydroxyvitamin D(3) (2) and 20-epi-2-methyl-1alpha,25-dihydroxyvitamin D(3) (3) were synthesized by palladium-catalyzed coupling reaction of A-ring 'enyne' synthons with CD-ring portions. The A-ring synthons were rationally synthesized via a novel and practical route, starting with methyl (R)-(+)- and (S)-(-)-3-hydroxy-2-methyl-propionate, in good yields. X-ray crystallographic analysis of 2alpha-methyl-1alpha,25-dihydroxyvitamin D(3) (2b) and conformational analysis of the A-ring of 2alpha-methyl-(2b) and 2beta-methyl-1alpha,25-dihydroxyvitamin D(3) (2f) were carried out, and the results are described. All A-ring diastereomers (2 and 3), thus synthesized, were biologically evaluated both in vitro and in vivo. The biologic potency was highly dependent on the stereochemistry of the A-ring substituents. In particular, 2b showed 4-fold higher vitamin D receptor [VDR] binding activity than the natural hormone, and its 20-epimer (3b) exhibited exceptionally high activity, 12-fold more potent in VDR binding, 7-fold in calcium mobilization, and 590-fold in induction of human promyelocytic leukemia (HL-60) cell differentiation as compared with the natural hormone. Further, the 20-epi-2beta-Me-1beta, 3alpha(OH)(2) isomer (3g) had significant biologic potencies compared to the natural hormone despite having 1beta-OH configuration. The transcriptional activities on human osteocalcin gene promoter, including VDRE in transfected mammalian cells, were also evaluated. Finally, there was a clear contrast between the effects of the 2-methyl group on the HL-60 cell differentiation- and apoptosis-inducing activities of 2 and 3.

Animals↗
PubMedDate not supplied

Aspects of teratology of vitamin A acid (beta-all-trans retinoic acid).

Retinoic acid must now be considered a normal metabolite of vitamin A. In fact, evidence now exists which can well support the idea that retinoic acid may itself be- or may be converted to-a metabolically active form which would carry out the growth-promoting functions of vitamin A. In contrast to retinol, retinoic acid is rapidly metabolized,being totally degraded within 48 hours after its adminstration to vitamin A-defiecient rats. Its primary excretory route is through the bile, the resulting metabolite retaining its intact side chain. At least one metabolite going through this excretory route has been identified as retinoyl-beta-glucuronide. However, retinoic acid undergoes oxidative decarboxylation of the terminal carbon to the extent of approximately 20%. Another 20% undergoes further degradation to lose the C-14. New chromatographic procedures as well as new extraction procedures which are gentle and give 100% recoveries have been described, which may be an important new tool in the elucidation of the metabolism of retinoic acid and retinol. So far at least eight metabolites of retinoic acid have been detected with these methods. However, none of these metabolites has yet been identified and their biological significance remains unknown.

Abnormalities, Drug-Induced↗