Side-chain oxidation of vitamin D3 in mouse kidney mitochondria: effect of the Hyp mutation and 1,25-dihydroxyvitamin D3 treatment

1987 ◽  
Vol 65 (10) ◽  
pp. 853-859 ◽  
Author(s):  
Glenville Jones ◽  
Agatha Yip ◽  
Harriet S. Tenenhouse
Keyword(s):  
Enzyme Activity ◽  
Mouse Kidney ◽  
Side Chain ◽  
Mitochondrial Enzyme ◽  
Renal Metabolism ◽  
Chain Oxidation ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

Side-chain oxidation of vitamin D is an important degradative pathway. In the present study we compared the enzymes involved in side-chain oxidation in normal and Hyp mouse kidney. Homogenates of normal mouse kidney catalyze the conversion of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3, 24-oxo-25-hydroxyvitamin D3, and 24-oxo-23,25-dihydroxyvitamin D3. After subcellular fractionation, total side-chain oxidative activity, estimated by the sum of the three products synthesized per milligram protein under initial rate conditions, coincided with the mitochondrial enzyme marker succinate–cytochrome-c reductase. Treatment of normal mice with 1,25-dihydroxyvitamin D3 (1.5 ng/g) resulted in an eightfold increase in mitochondrial enzyme activity, with no change in apparent Km but a significant rise in Vmax. With 24,25-dihydroxyvitamin D3 as the substrate, normal renal mitochondria produced 24-oxo-25-hydroxyvitamin D3 and 24-oxo-23,25-dihydroxyvitamin D3, and the synthesis of these metabolites could be increased sixfold by pretreatment with 1,25-dihydroxyvitamin D3. In the Hyp mouse, the side-chain oxidation pathway showed similar subcellular distribution of enzyme activity. However, product formation from 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 was twofold greater in mutant than in normal mitochondria. Furthermore, 1,25-dihydroxyvitamin D3 pretreatment of Hyp mice resulted in a 3.4-fold increase over basal metabolism of both 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3. These results demonstrate that (i) kidneys from normal and Hyp mice possess basal and 1,25-dihydroxyvitamin D3 inducible enzyme system(s) in the mitochondrial fraction, which catalyze the side-chain oxidation of 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3, and (ii) the Hyp mutation appears to perturb the renal metabolism of both substrates only in the basal state.

Metabolism of 25-hydroxyvitamin D3 in rats: low-calcium diet vs. calcitriol infusion

1992 ◽  
Vol 262 (3) ◽  
pp. E359-E367 ◽  
Author(s):  
M. J. Bolt ◽  
W. E. Jensen ◽  
M. D. Sitrin
Keyword(s):  
Side Chain ◽  
Metabolic Clearance ◽  
Chain Oxidation ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Low Calcium Diet ◽  
Subsequent Degradation ◽  
Dramatic Rise ◽  
25 Hydroxyvitamin D

It has been proposed that the decreased serum level of 25-hydroxyvitamin D [25(OH)D] observed with dietary Ca restriction is mediated by an increase in circulating 1,25-dihydroxyvitamin D [1,25(OH)2D]. We compared the effects of endogenous and exogenous elevations in serum 1,25(OH)2D on the production rate (PR), metabolic clearance rate (MCR), and excretory pathways of [3H]25(OH)D3 in rats, with the use of steady-state techniques. Low-Ca diet and 1,25(OH)2D3 infusion caused comparable reductions in serum 25(OH)D and elevations in 1,25(OH)2D. Low-Ca diet lowered serum 25(OH)D by increasing MCR from 21.8 +/- 3.2 to 29.1 +/- 5.4 (SD) microliters.min-1.kg-1 (P less than or equal to 0.005) and decreasing PR from 944 +/- 161 to 663 +/- 163 pg.Ain-1.kg-1 (P less than or equal to 0.001). In contrast, 1,25(OH)2D3 infusion produced a dramatic rise in the MCR of 25(OH)D from 23.4 +/- 4.5 to 62.8 +/- 13.7 microliters.min-1.kg-1 (P less than or equal to 0.001) and also increased the PR from 943 +/- 165 to 1,500 +/- 337 pg.min-1.kg-1 (P less than or equal to 0.001). With 1,25(OH)2D3 infusion, urinary excretion of metabolites of [3H]25(OH)D3 rose rapidly, and kidney homogenates from these rats demonstrated vigorous side-chain oxidation of [3H]25(OH)D3. With low-Ca diet, urinary tritium excretion increased more gradually, and no direct side-chain oxidation of [3H]25(OH)D3 occurred in vitro. The increased MCR of 25(OH)D3 with low-Ca diet could be accounted for by enhanced synthesis of 1,25(OH)2D3 and subsequent degradation in target tissues.

An international comparison of vitamin D metabolite measurements.

1984 ◽  
Vol 30 (3) ◽  
pp. 399-403 ◽  
Author(s):  
M J Jongen ◽  
F C Van Ginkel ◽  
W J van der Vijgh ◽  
S Kuiper ◽  
J C Netelenbos ◽  
...  
Keyword(s):  
Reference Sample ◽  
Plasma Samples ◽  
Internal Reference ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Three Samples ◽  
25 Hydroxyvitamin D ◽  
Laboratory Survey ◽  
Standard Solutions

Abstract An international 19-laboratory survey was organized to compare assays for 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D in plasma. Each participant received two ethanolic standard solutions of each metabolite and eight plasma samples. Each laboratory used its usual procedures. Mean interlaboratory coefficients of variation (CVs) for the eight plasma samples were 35%, 43%, and 52% for 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D, respectively. Average CVs for the standard solutions were 27%, 23%, and 25%, respectively. Of the eight plasma samples, five had the same concentration for one of the metabolites. One sample was diluted to 0.6 times its original concentration and three samples were fortified with one or more of the metabolites under investigation. Fourteen of 18 laboratories (78%) could distinguish between the five unchanged samples and the modified ones with their 25-hydroxyvitamin D assay. Nine of 12 (75%) could distinguish the modified samples from the other samples with the 24,25-dihydroxyvitamin D assay. Only eight of 15 (53%) could do this their 1,25-dihydroxyvitamin D assay. Values from different laboratories evidently cannot be intercompared without making an actual comparison of the assay procedures. Furthermore, in case of clinical applications of these assays, each laboratory should establish its own reference values and should continually use an internal reference sample to assess the precision of the procedures.

scholarly journals Plasma 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D and Risk of Incident Ovarian Cancer

2007 ◽  
Vol 16 (4) ◽  
pp. 783-788 ◽  
Author(s):  
Shelley S. Tworoger ◽  
I-Min Lee ◽  
Julie E. Buring ◽  
Bernard Rosner ◽  
Bruce W. Hollis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

scholarly journals Hypercalcemia associated with cosmetic injections: a systematic review

2018 ◽  
Vol 178 (4) ◽  
pp. 425-430 ◽  
Author(s):  
Niranjan Tachamo ◽  
Anthony Donato ◽  
Bidhya Timilsina ◽  
Salik Nazir ◽  
Saroj Lohani ◽  
...  
Keyword(s):  
Body Parts ◽  
Common Complication ◽  
Common Site ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Paraffin Oil ◽  
Initial Procedure ◽  
Life Threatening ◽  
25 Hydroxyvitamin D

Introduction Cosmetic injections with silicone and polymethylmethacrylate are not FDA approved for augmentation of body parts such as breast, buttock or legs, but they have been widely used for decades. Cosmetic injections can cause foreign body granulomas and occasionally severe and life-threatening hypercalcemia. We aimed to systematically analyze the published literature on cosmetic injection-associated hypercalcemia. Methods We searched relevant articles on hypercalcemia associated with various cosmetic injections and extracted relevant data on demographics, cosmetic injections used, severity of hypercalcemia, management and outcomes. Results We identified 23 eligible patients from 20 articles. Mean age was 49.83 ± 14.70 years with a female preponderance (78.26% including transgender females). Silicone was most commonly used, followed by polymethylmethacrylate and paraffin oil (43.48, 30.43, and 8.70% respectively). The buttock was the most common site followed by the breast (69.57% and 39.13% respectively). Hypercalcemia developed at mean duration of 7.96 ± 7.19 years from the initial procedure. Mean ionized calcium at presentation was 2.19 ± 0.61 mmol/L and mean corrected calcium at presentation was 3.43 ± 0.31 mmol/L. 1,25-Dihydroxyvitamin D (1,25(OH)2D or calcitriol) was elevated while 25-hydroxyvitamin D (25(OH)D) and PTH were low in majority of cases. Hypercalcemia was managed conservatively with hydration, corticosteroids and bisphosphonates in majority of cases. Surgery was attempted in 2 cases but was unsuccessful. Renal failure was the most common complication (82.35% cases) and 2 patients died. Conclusion Hypercalcemia from cosmetic injections can be severe and life threatening and can present years after the initial procedure. Cosmetic injection-associated granuloma should be considered a cause of hypercalcemia, especially in middle-aged females presenting with non-PTH-mediated, non-malignant hypercalcemia, which is often associated with elevated calcitriol; however, it should be noted that calcitriol level may be normal as well.

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