Vitamin D hydroxylases

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Abstract
There are three mixed function oxidases which catalyze hydroxylations of vitamin D and its derivatives. These include the hepatic mitochondrial or microsomal vitamin D3‐25‐hydroxylase and the two renal mitochondrial enzymes which further hydroxylate 25‐hydroxyvitamin‐D3 (25‐OH‐D3) to form 24R,25‐dihydroxyvitamin D3 (24,25(OH)2D3) and 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3], the primary steroid hormonal derivative of vitamin D3. All three enzymes are cytochrome P450 dependent. The two renal mitochondrial enzymes are regulated, usually in a reciprocal fashion. The intracellular signalling systems involved in this regulation include 1,25(OH)2D3 itself and both protein kinases A and C. Recent progress has been made in the purification and cloning of the vitamin D3‐25‐hydroxylase and the 25‐OH‐D3‐24‐hydroxylase. When the 25‐OH‐D3‐1‐hydroxylase is purified and cloned, efforts which have thus far been frustrated by its low abundance, fertile new ground for the study of the regulation of vitamin D metabolism at the molecular level will be opened up.

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