PhysiologyTier 1Medical Sciences concept

Vitamin D metabolism (hepatic 25-hydroxylation, renal 1-alpha-hydroxylation)

Core concept

Two hydroxylations, two organs
- Skin: 7-dehydrocholesterol + UVB (290-315 nm) -> previtamin D3 -> cholecalciferol (D3)
  - Diet supplies ergocalciferol (D2) and D3; D3 raises 25(OH)D more effectively than D2
- Liver: 25-hydroxylase (CYP2R1, CYP27A1) -> 25(OH)D (calcidiol)
  - Substrate-driven, barely regulated -> the storage form and the one to measure; t-half ~2-3 weeks
- Kidney, proximal tubule: 1-alpha-hydroxylase (CYP27B1) -> 1,25(OH)2D (calcitriol)
  - Tightly regulated - the active hormone; t-half ~4-6 h
Regulation of 1-alpha-hydroxylase
- Stimulated by: PTH, hypophosphataemia, hypocalcaemia, low FGF23
- Inhibited by: FGF23, calcitriol itself (negative feedback), hyperphosphataemia
Inactivation: 24-hydroxylase (CYP24A1) -> 24,25(OH)2D and calcitroic acid; induced by FGF23 and calcitriol
Actions of calcitriol (VDR - a nuclear receptor, heterodimerises with RXR)
- Gut: inc calcium absorption (TRPV6, calbindin) - the dominant action; inc phosphate absorption
- Bone: inc RANKL on osteoblasts -> osteoclast activation (mobilises calcium); permissive for mineralisation
- Parathyroid: dec PTH gene transcription
- Kidney: inc calcium reabsorption; inc FGF23

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