A cytochrome P450 monooxygenase involved in vitamin D metabolism and in calcium and phosphorus homeostasis. Catalyzes the rate-limiting step in the activation of vitamin D in the kidney, namely the hydroxylation of 25-hydroxyvitamin D3/calcidiol at the C1-alpha position to form the hormonally active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3/calcitriol that acts via the vitamin D receptor (VDR) (PubMed:15972816, PubMed:10092858). Has 1-alpha-hydroxylase activity on vitamin D intermediates of the CYP24A1-mediated inactivation pathway. Converts 24R,25-dihydroxyvitamin D3/secalciferol to 1-alpha,24,25-trihydroxyvitamin D3, an active ligand of VDR. Also active on 25-hydroxyvitamin D2 (By similarity). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:15972816, PubMed:10092858). calcidiol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = calcitriol + H2O + 2 oxidized [adrenodoxin] 2 H(+) + O2 + 2 reduced [adrenodoxin] + secalciferol = calcitetrol + H2O + 2 oxidized [adrenodoxin] 25-hydroxy-24-oxocalciol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (1S)-1,25-dihydroxy-24-oxocalciol + H2O + 2 oxidized [adrenodoxin] 25-hydroxyvitamin D2 + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 1alpha,25-dihydroxyvitamin D2 + H2O + 2 oxidized [adrenodoxin] Activated by cardiolipin and dioleoyl phosphatidylethanolamine (DOPE), phospholipids found in the inner mitochondrial membrane. Inhibited by high substrate concentration. Hormone biosynthesis; vitamin D biosynthesis. Kidney. Belongs to the cytochrome P450 family.