The 24-hydroxylation of 1,25-dihydroxyvitamin D3

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.