Metabolism of tritiated vitamin D

Abstract

Methods of labelling calciferol in specified positions with tritium have been investigated with the purpose of selecting a stable and highly radioactive compound for metabolic studies. [3 α - 3 H]Ergocalciferol and [24, 25, 26, 27- 3 H 9 ]-, [7- 3 H]-, [6- 3 H]- and [1 α - 3 H]-cholecalciferol have been prepared and the excretion and distribution in the body of vitamin D activity and radioactivity after administration to young rachitic rats has been studied. It is concluded that [1 α - 3 H]cholecalciferol is a suitable tritium-labelled form of vitamin D for further meta­bolic studies. The more notable results of the present studies are that much of the tritium from variously tritiated calciferols finds its way into the body water, and that break-down products of calciferol are to be found in the more polar fractions of the extracts of faeces, into which they pass from the bile.

Metabolism of Vitamin D3-3H in Human Subjects: Distribution in Blood, Bile, Feces, and Urine*

“…From the present and previous data (5,8), it is obvious that it is no longer correct to assume that antirachitic activity of plasma is synonymous with unaltered vitamin D3. Clearly, much of the antirachitic effectiveness must be attributed to a polar metabolite of vitamin D (peak 4, Figure 2) that is easily separated on silicic acid from the unaltered vitamin.…”

“…The steroid was administered intravenously with the subject in the fasting state in the morning over a period of approximately 30 to 45 seconds. Fifteen-to 20-ml samples of heparinized blood were collected at 5, 15, 30, and 45 minutes and at 1,2,4,8,12,16, and 24 hours. For the subsequent 24 hours plasma was obtained at 12-hour intervals.…”

“…The chloroform extract of the serum was chromatographed on silicic acid columns as described previously, using gradient elution techniques (3,5). 8 5 i 0.5 (4.0 IU/rat) * Fractions refer to those shown in Figure 2. Fractions 3 and 4 were bioassayed by the line test technique (21).…”

“…The tissue distribution of radioactively labeled vitamins D2 and D3 administered orally or parenterally has been studied in the past, primarily in rachitic or normal rats and chicks, by DeLuca and co-workers (1-7), Callow, Kodicek, and Thompson (8), Bosmann and Chen (9), Schachter, Finkelstein, and Kowarski (10), and Nair and Bucana (11). Limited data are also available on the fate of an oral dose of radioactive vitamin D * Submitted for publication December 6, 1966;ac-cepted March 6, 1967. Supported in part by grants AM06404 and AM11247…”

Metabolism of Vitamin D3-3H in Vitamin D-Resistant Rickets and Familial Hypophosphatemia*

“…Radioautographs of bone obtained after radioactive vitamin D injection demonstrate localized radioactivity in'the cytoplasm of chondrocytes in the proliferating cartilage zone of growing bone (26); experiments by Lund and DeLuca (9,13) reveal that the peak 4 metabolite represents the majority of radioactivity in rat bone while vitamin D, itself, is present in only small amounts. Furthermore, the peak 4 metabolite has been shown to be as biologically active as the parent vitamin in curing rickets in rats (9,12).…”