Determination of stereochemical configuration of the 24-hydroxyl group of 24,25-dihydroxyvitamin D3 and its biological importance

Tanaka, Yoko; DeLuca, Hector F.; Ikekawa, Nobuo; Morisaki, Masuo; Koizumi, Naoyuki

doi:10.1016/0003-9861(75)90157-5

Cited by 108 publications

(20 citation statements)

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“…The occurrence of small concentrations of 24,25 (OH) 2 D in serum could be explained by the presence of another enzyme, Cyp27A1, which catalyzes multiple hydroxylation steps involving vitamin D metabolites (29). The naturally occurring 24,25(OH) 2 D has the 24(R) configuration (30) (Figure 1). Finally, our patients had bi-allelic mutations in the CYP24A1 gene.…”

Section: Discussionmentioning

confidence: 99%

1,25-(OH)2D-24 Hydroxylase (CYP24A1) Deficiency as a Cause of Nephrolithiasis

Nesterova

Malicdan

Yasuda

et al. 2013

Clinical Journal of the American Society of Nephrology

141

119

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SummaryBackground and objectives Elevated serum vitamin D with hypercalciuria can result in nephrocalcinosis and nephrolithiasis. This study evaluated the cause of excess 1,25-dihydroxycholecalciferol (1a,25(OH) 2 D 3 ) in the development of those disorders in two individuals.Design, setting, participants, & measurements Two patients with elevated vitamin D levels and nephrocalcinosis or nephrolithiasis were investigated at the National Institutes of Health (NIH) Clinical Center and the NIH Undiagnosed Diseases Program, by measuring calcium, phosphate, and vitamin D metabolites, and by performing CYP24A1 mutation analysis.Results Both patients exhibited hypercalciuria, hypercalcemia, low parathyroid hormone, elevated vitamin D (1a,25(OH) 2 D 3 ), normal 25-OHD 3 , decreased 24,25(OH) 2 D, and undetectable activity of 1,25(OH) 2 D-24-hydroxylase (CYP24A1), the enzyme that inactivates 1a,25(OH) 2 D 3 . Both patients had bi-allelic mutations in CYP24A1 leading to loss of function of this enzyme. On the basis of dbSNP data, the frequency of predicted deleterious bi-allelic CYP24A1 variants in the general population is estimated to be as high as 4%-20%. ConclusionsThe results of this study show that 1,25(OH) 2 D-24-hydroxylase deficiency due to bi-allelic mutations in CYP24A1 causes elevated serum vitamin D, hypercalciuria, nephrocalcinosis, and renal stones.

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Section: Discussionmentioning

confidence: 99%

1,25-(OH)2D-24 Hydroxylase (CYP24A1) Deficiency as a Cause of Nephrolithiasis

Nesterova

Malicdan

Yasuda

et al. 2013

Clinical Journal of the American Society of Nephrology

141

119

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“…This has been established first by preparing [3] synthetically the two C-25 epimers of 25,26(OH)?D3 and assigning [4] their respective configurations by X-ray studies. [7] identified with 24R,25(OH)2Dg. But while the natural 24R,25(OH)2D3 was superior to the synthetic 24s epimer in elevating serum phosphorus and in the calcification of bone in rachitic rats [7] , the natural 25R,26(OH)2D3 is surprisingly less effective [3] than 25S,26(OH)2D3 in this biological system.…”

Section: Discussionmentioning

confidence: 99%

“…[7] identified with 24R,25(OH)2Dg. But while the natural 24R,25(OH)2D3 was superior to the synthetic 24s epimer in elevating serum phosphorus and in the calcification of bone in rachitic rats [7] , the natural 25R,26(OH)2D3 is surprisingly less effective [3] than 25S,26(OH)2D3 in this biological system. The natural 25 ,26(OH)*D3 isolated from porcine plasma has been found [5] inactive in the cure of rickets in rats.…”

Section: Discussionmentioning

confidence: 99%

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The absolute configuration of the natural 25,26‐dihydroxycholecalciferol

et al. 1978

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“…The less polar peak was separated into two major peaks on a reversephase HPLC (Fig. 1B) (15). The trimethylsilyl ether of the 24,25-(OH)2D3 isolated by incubating 25-OH-24-oxo-D3 with kidney homogenates from vitamin D-supplemented chickens comigrated with the trimethylsilyl ether of the authentic 24S,25-(OH)2D3 (Fig.…”

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confidence: 99%