The 24-hydroxylation of 1,25-dihydroxyvitamin D3

• Published in: The Journal of biological chemistry Vol. 252; no. 4; pp. 1421 - 1424
• Main Authors: Tanaka, Y, Castillo, L, DeLuca, H F
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 25.02.1977
• Subjects: Animals; Chickens; Dihydroxycholecalciferols - metabolism; Hydroxycholecalciferols - biosynthesis; Hydroxycholecalciferols - metabolism; Hydroxycholecalciferols - pharmacology; Kidney - drug effects; Kidney - enzymology; Male; Mitochondria - drug effects; Mitochondria - enzymology; Nephrectomy; Rats; Steroid Hydroxylases - metabolism; Vitamin D Deficiency - enzymology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)40673-9

The production of 1,24,25-trihydroxyvitamin D3 in vivo in vitamin D-deficient rats has been demonstrated from either 25-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3. The stereochemical configuration of the hydroxyl on the 24 position of 1,24,25-trihydroxyvitamin D3 has also been unambiguously established to be R. Nephrectomy failed to eliminate the conversion of 1,25-dihydroxyvitamin D3 to the 1,24,25-trihydroxyvitamin D3, establishing that the 24-hydroxylase can be demonstrated in at least one organ in addition to kidney in contrast to the 1-hydroxylase. 1,24,25-Trihydroxyvitamin D3 can also be produced in vivo from 1alpha-hydroxyvitamin D3 or from 24-hydroxyvitamin D3, analogs of vitamin D3 which are not naturally occurring. Using chick kidney mitochondrial preparations it has been demonstrated that the 24-hydroxylase is able to utilize 1,25-dihydroxyvitamin D3 as a substrate whereas it is unable to utilize 1alpha-hydroxyvitamin D3. In addition, the chicke kidney 1-hydroxylase is known to convert 24,25-dihydroxyvitamin D3 to the 1,24,25-trihydroxyvitamin D3, but this hydroxylase is unable to act on the 24-hydroxyvitamin D3. These results demonstrate that the renal vitamin D hydroxylases require that a hydroxyl be on the 25 carbon of the vitamin D molecule before it can be 1- or 24-hydroxylated.