Vitamin D3 (cholecalciferol) undergoes sequential hydroxylation to become active 1,25-dihydroxycholecalciferol (calcitriol). Which hydroxylase step is the tightly regulated, physiologically critical step, and what is its principal inducer?

• A 25-hydroxylase in the liver; induced by low dietary calcium
• B 24-hydroxylase in the kidney; induced by low serum phosphate and dietary vitamin D excess
• C 26-hydroxylase in skin fibroblasts; induced by UV-B radiation
• D 1-alpha-hydroxylase in the kidney; induced by parathyroid hormone (PTH) and low serum phosphate ✓

Explanation

The rate-limiting and tightly regulated step in calcitriol synthesis is the 1-alpha-hydroxylation of 25-hydroxyvitamin D in the kidney (mitochondrial CYP27B1). This step is powerfully induced by PTH (responding to hypocalcemia) and by hypophosphatemia (mediated via FGF-23 suppression). Calcitriol itself suppresses CYP27B1 via negative feedback and induces 24-hydroxylase (CYP24A1) to generate inactive 24,25-dihydroxyvitamin D. The hepatic 25-hydroxylation step is not tightly regulated and reflects vitamin D nutritional status rather than calcium/phosphate homeostasis.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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