Enhancement of the production of 1,25-dihydroxyvitamin D3 in chick kidney mitochondria by an extramitochondrial factor.

The 1 alpha-hydroxylation of 25-hydroxyvitamin D3 (25-hydroxycholecalciferol) by isolated chick kidney mitochondria is stimulated 1.5-4.0-fold by a factor or factors in postmitochondrial and postmicrosomal supernatants of homogenates of chick kidney. The stimulatory factor is heat-stable, dialyzable, and trypsin-sensitive and does not appear in lipid extracts of cytosol. The stimulatory effect of cytosol was quantitatively similar over a 4-fold range in substrate concentration and a 5-fold enzyme concentration range. Cytosol did not appear to increase substrate availability to the mitochondria as determined by measurement of substrate and products in mitochondria following incubation with [3H]25-hydroxyvitamin D3. The stimulatory activity is equivalent in cytosolic fractions from kidneys of vitamin D-deficient and replete chicks and is also present in brain and liver tissue. These latter observations suggest that the stimulatory factor (or factors) is not involved in the regulation of the 25-hydroxy-vitamin-D3-1-hydroxylase.