Vitamin D Activation

1. 1

   7-Dehydrocholesterol + UVB -> previtamin D3 -> cholecalciferol (D3)

   Non-enzymatic photolysis (UVB ~290-315 nm) ST-0360 Irreversible/directional
   In 7-Dehydrocholesterol UVB

   Out Previtamin D3
   › Notes

   Occurs in the epidermis; limited by skin pigmentation, latitude, season and sunscreen.

2. 2

   Cholecalciferol -> 25-hydroxycholecalciferol (calcidiol)

   Vitamin D 25-hydroxylase (CYP2R1/CYP27A1) 1.14.14.24 ST-0361 Irreversible/directional NADPH O2
   In Cholecalciferol (vitamin D3)

   Out 25-Hydroxycholecalciferol
   › Notes

   Hepatic and essentially unregulated, so serum 25-OH-D is the storage form and the assay used to assess vitamin D status.

3. 3

   25-Hydroxyvitamin D -> 1,25-dihydroxyvitamin D (calcitriol)

   1-alpha-hydroxylase (CYP27B1) 1.14.15.18 ST-0362 Irreversible rate-limiting NADPH O2
   In 25-Hydroxyvitamin D (calcidiol)

   Out 1,25-Dihydroxyvitamin D
   › Notes

   Rate-limiting and tightly regulated step, in the proximal renal tubule: up-regulated by PTH and hypophosphataemia, suppressed by FGF-23 and by calcitriol itself.

4. 4

   25-OH-D or calcitriol -> 24,25-(OH)2-D / calcitroic acid

   24-Hydroxylase (CYP24A1) 1.14.15.16 ST-0363 Irreversible/directional NADPH O2
   In 25-OH-D or calcitriol

   Out 24,25-(OH)2-D / calcitroic acid
   › Notes

   Inactivation arm; induced by calcitriol. Loss-of-function causes idiopathic infantile hypercalcaemia.

Showing all 4 steps.