1 alpha-hydroxylation of 24-hydroxyvitamin D2 represents a minor physiological pathway for the activation of vitamin D2 in mammals.

C24-Hydroxylation was evaluated as a possible activation pathway for vitamin D2 and vitamin D3. Routine assays showed that 24-hydroxyvitamin D2 and 1,24-dihydroxyvitamin D2 could be detected in rats receiving physiological doses (100 IU/day) of vitamin D2; however, 24-hydroxyvitamin D3 could not be detected in rats receiving similar doses of vitamin D3. In rats, 24-hydroxyvitamin D2 was very similar to 25-hydroxyvitamin D2 at stimulating intestinal calcium transport and bone calcium resorption. The biological activity of 24-hydroxyvitamin D2 was eliminated by nephrectomy, suggesting that 24-hydroxyvitamin D2 must undergo 1 alpha-hydroxylation to be active at physiological doses. In vivo experiments suggested that when given individually to vitamin D deficient rats, 24-hydroxyvitamin D2, 25-hydroxyvitamin D2, and 25-hydroxyvitamin D3 were 1 alpha-hydroxylated with the same efficiency. However, when presented simultaneously, 24-hydroxyvitamin D2 was less efficiently 1 alpha-hydroxylated than either 25-hydroxyvitamin D3 or 25-hydroxyvitamin D2. 1,24-Dihydroxyvitamin D2 was also approximately 2-fold less competitive than either 1,25-dihydroxyvitamin D2 or 1,25-dihydroxyvitamin D3 for binding sites on the bovine thymus 1,25-dihydroxyvitamin D receptor. These results demonstrate that 24-hydroxylation followed by 1 alpha-hydroxylation of vitamin D2 represents a minor activation pathway for vitamin D2 but not vitamin D3.

[1]  N. Koszewski,et al.  Metabolism of vitamin D2 in pig liver homogenates: evidence for a free radical reaction. , 1989, Archives of biochemistry and biophysics.

[2]  N. Koszewski,et al.  24,26-Dihydroxyvitamin D2: a unique physiological metabolite of vitamin D2. , 1988, Biochemistry.

[3]  R. Horst,et al.  Evidence that discrimination against ergocalciferol by the chick is the result of enhanced metabolic clearance rates for its mono- and dihydroxylated metabolites. , 1988, The Journal of nutrition.

[4]  M. Uskoković,et al.  Use of Fourier transform 1H NMR in the identification of vitamin D2 metabolites. , 1987, Analytical biochemistry.

[5]  B. R. Thomas,et al.  Isolation and identification of 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3, a new metabolite of 1,25-dihydroxyvitamin D3 produced in rat kidney. , 1987, Biochemistry.

[6]  Reddy Gs,et al.  Isolation and identification of 1,24,25-trihydroxyvitamin D2, 1,24,25,28-tetrahydroxyvitamin D2, and 1,24,25,26-tetrahydroxyvitamin D2: new metabolites of 1,25-dihydroxyvitamin D2 produced in rat kidney. , 1986 .

[7]  N. Koszewski,et al.  24-Hydroxylation of 1,25-dihydroxyergocalciferol. An unambiguous deactivation process. , 1986, The Journal of biological chemistry.

[8]  N. Koszewski,et al.  [14] Isolation and identification of vitamin D metabolites , 1986 .

[9]  H. Orimo,et al.  Long-term treatment of postmenopausal osteoporosis with active vitamin D3, 1-alpha-hydroxycholecalciferol (1 alpha-OHD3) and 1, 24 Dihydroxycholecalciferol (1, 24(OH)2D3). , 1985, Endocrinologia japonica.

[10]  P. Wovkulich,et al.  (23S)-1,23,25-Trihydroxyvitamin D3: its biologic activity and role in 1 alpha,25-dihydroxyvitamin D3 26,23-lactone biosynthesis. , 1984, Biochemistry.

[11]  R. Horst,et al.  The isolation and identification of vitamin D2 and vitamin D3 from Medicago sativa (alfalfa plant). , 1984, Archives of biochemistry and biophysics.

[12]  J. L. Napoli,et al.  Production of C-24- and C-23-oxidized metabolites of 1,25-dihydroxycholecalciferol by cultured kidney cells (LLC PK1) and their presence in kidney in vivo. , 1984, The Biochemical journal.

[13]  A. Norman,et al.  Isolation and identification of 1 alpha,25-dihydroxy-24-oxovitamin D3, 1 alpha,25-dihydroxyvitamin D3 26,23-lactone, and 1 alpha,24(S),25-trihydroxyvitamin D3: in vivo metabolites of 1 alpha,25-dihydroxyvitamin D3. , 1984, Biochemistry.

[14]  R. Horst,et al.  25-hydroxyvitamin D 1α- and 24-hydroxylase activities in pig kidney homogenates: effect of vitamin D deficiency , 1984 .

[15]  R. Horst,et al.  C(24)- and C(23)-oxidation, converging pathways of intestinal 1,25-dihydroxyvitamin D3 metabolism: identification of 24-keto-1,23,25-trihydroxyvitamin D3. , 1983, Biochemistry.

[16]  A. Norman,et al.  Isolation and identification of 1,25-dihydroxy-24-oxo-vitamin D3 and 1,23,25-trihydroxy-24-oxo-vitamin D3. New metabolites of vitamin D3 produced by a C-24 oxidation pathway of metabolism for 1,25-dihydroxyvitamin D3 present in intestine and kidney. , 1983, The Journal of biological chemistry.

[17]  G. Jones,et al.  The isolation and identification of two new metabolites of 25-hydroxyvitamin D3 produced in the kidney. , 1983, The Journal of biological chemistry.

[18]  H. DeLuca,et al.  Biological Activity of 1,24(R)-Dihydroxyvitamin 3 and 1,24(S)-Dihydroxyvitamin D3 in the Rat 1 , 1982, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[19]  R. Horst,et al.  Discrimination in the metabolism of orally dosed ergocalciferol and cholecalciferol by the pig, rat and chick. , 1982, The Biochemical journal.

[20]  D. Beitz,et al.  1,24,25-Trihydroxyvitamin D3: a circulating metabolite in vitamin D2-treated bovine. , 1982, Archives of biochemistry and biophysics.

[21]  M. Uskoković,et al.  1 Alpha-25,26-trihydroxyvitamin D3: an in vivo and in vitro metabolite of vitamin D3. , 1981, Biochemistry.

[22]  R. Horst,et al.  Quantitation of vitamin D and its metabolites and their plasma concentrations in five species of animals. , 1981, Analytical biochemistry.

[23]  H. DeLuca,et al.  1,25,26-trihydroxyvitamin D3: isolation, identification, and biological activity. , 1981, Archives of biochemistry and biophysics.

[24]  H. DeLuca,et al.  Isolation of identification of 24(R)-hydroxyvitamin D3 from chicks give large doses of vitamin D3. , 1981, Biochemistry.

[25]  H. DeLuca,et al.  Isolation and identification of 24-hydroxyvitamin D2 and 24,25-dihydroxyvitamin D2. , 1980, Archives of biochemistry and biophysics.

[26]  H. DeLuca,et al.  Isolation and characterization of 1 alpha-hydroxy-23-carboxytetranorvitamin D: a major metabolite of 1,25-dihydroxyvitamin D3. , 1979, Biochemistry.

[27]  H. DeLuca,et al.  Rat intestinal 25-hydroxyvitamin D3- and 1alpha,25-dihydroxyvitamin D3-24-hydroxylase. , 1978, The Journal of biological chemistry.

[28]  C. Christiansen,et al.  Actions of vitamins D2 and D3 and 25-OHD3 in anticonvulsant osteomalacia. , 1975, British medical journal.

[29]  H. DeLuca,et al.  1,24,25-Trihydroxyvitamin D3. A metabolite of vitamin D3 effective on intestine. , 1973, The Journal of biological chemistry.

[30]  H. DeLuca,et al.  Metabolism of vitamin D2 and vitamin D3 in the rachitic chick , 1967 .

[31]  H. Steenbock,et al.  THE REACTION OF THE CHICKEN TO IRRADIATED ERGOSTEROL AND IRRADIATED YEAST AS CONTRASTED WITH THE NATURAL VITAMIN D OF FISH LIVER OILS , 1932 .