Vitamin D2 (ergocalciferol) metabolism
Vitamin D2 (ergocalciferol) metabolism The first step of Vitamin D2 metabolism is a side-chain hydroxylation in theliver carried out by specific cytochrome P450 enzymes. The hydroxylation reactions can becatalyzed by Cytochrome P450, family 3, subfamily A, polypeptide 4 ( CYP3A4 ),  and Cytochrome P450, family 27, subfamily A,polypeptide 1 ( CYP27A1 ) , , ,,  and result in formation of 24-OH-vitamin D2metabolite. Alternatively the reactions can be catalyzed by CYP27A1 , CYP3A4 , , Cytochrome P450, family 2,subfamily C, polypeptide 9 ( CYP2C9 )  and cytochrome CytochromeP450, family 2, subfamily R, polypeptide 1 ( CYP2R1 ) , ,  to produce 25-OH-vitamin D2 metabolite. Vitamin D2 analogue Doxercalciferol is also hydroxylated by CYP27A1 andCYP3A4 to form 1,24-Dihydroxyvitamin D2 , ,,  and 1,25-Dihydroxyvitamin D2 , as products. The latter metabolites are also formed during thesubsequent metabolic steps in kidney. In particular, 1,24-Dihydroxyvitamin D2 and1,25-Dihydroxyvitamin D2 are products of hydroxylation of, respectively,24-OH-vitamin D2 and 25-OH-vitamin D2 catalyzed by Cytochrome P450, family27, subfamily B, polypeptide 1 ( CYP27B1 ) , ,. 1,24-Dihydroxyvitamin D2 is further hydroxylated by CYP27A1 andcytochrome Cytochrome P450, family 24, subfamily A, polypeptide 1 ( CYP24A1 ) toform a 1-alpha,24,26-trihydroxy-vitamin D2 trihydroxylated metabolite ,  that undergoes subsequent oxidation at C-26 catalyzed byCYP24A1 ,  with1alpha-,24-dihydroxy-26-carboxy-vitamin D2 as a product. 25-OH-vitamin D2 can be further hydroxylated by CYP24A1 when a24,25-Dihydroxyvitamin D2 metabolite is formed . The same P450 enzyme catalyzes all further steps of 1,25-Dihydroxyvitamin D2degradation that include: hydroxylation at C-24 to form 1-alfa-,24-,25-(OH)3-vitaminD2 as a product and subsequent hydroxylation at C-28 to form1-alfa-,24-,25-,28-(OH)4-vitamin D2. The following hydroxyl group migrationresults in production of stereo isomers of which only1-alfa-,24(R)-,25-,26-Tetrahydroxy-Vitamin D2 participates in C-24 hydroxyl groupoxidation to form 1alfa-,25-,26-trihydroxy-24-oxo-vitamin D2 metabolite. Thismetabolite is then hydroxylated to 1alpha-,23-,25-,26-tetrahydroxy-24-oxo-vitaminD2 and undergoes a side-chain degradation to1,23-Dihydroxy-24,25,26,27-tetranorvitamin D3. At the final stage, the lattermetabolite is oxidized to form Calcitroic acid.