Vitamin D3 (cholecalciferol) undergoes two hydroxylation steps before becoming the active hormone. Which is the physiologically regulated, rate-limiting hydroxylation step, and what stimulates it?
- A 25-hydroxylation in liver; stimulated by low serum 25(OH)D3
- B 1-alpha-hydroxylation in the liver; stimulated by FGF-23
- C 1-alpha-hydroxylation in the kidney; stimulated by PTH and low serum phosphate ✓
- D 24-hydroxylation in kidney; stimulated by high serum calcium
Correct answer: C. 1-alpha-hydroxylation in the kidney; stimulated by PTH and low serum phosphate
Explanation
The first step (25-hydroxylation by CYP2R1/CYP27A1 in the liver) is largely unregulated; circulating 25(OH)D3 reflects dietary intake and sun exposure. The second step, 1-alpha-hydroxylation (by CYP27B1 mitochondrial enzyme in the proximal tubule), is tightly regulated: it is stimulated by PTH, low phosphate, and low calcium, and is inhibited by FGF-23 and high 1,25(OH)2D3 (which instead induces the catabolic 24-hydroxylase, CYP24A1). The active hormone is 1,25(OH)2D3 (calcitriol).
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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