A 4-year-old child from a low-income household presents with bowed legs, widening of the wrists, and a rachitic rosary on chest examination. Serum calcium is low, phosphate is low, and parathyroid hormone (PTH) is elevated. 25-hydroxyvitamin D is severely deficient. In which organ does the hydroxylation of 25-OH-D3 to the biologically active 1,25-(OH)2-D3 (calcitriol) primarily occur?

• A Kidney (by 1-alpha-hydroxylase) ✓
• B Liver (by 25-hydroxylase)
• C Skin (by UV-B photolysis)
• D Intestine (by enterocyte vitamin D-binding enzyme)

Explanation

The final activation step occurs in the kidney: 25-hydroxycholecalciferol (calcidiol) is converted to 1,25-dihydroxycholecalciferol (calcitriol) by mitochondrial 1-alpha-hydroxylase (CYP27B1) in proximal tubular cells. This step is stimulated by elevated PTH, low calcium, and low phosphate — all present in this child with nutritional rickets. The liver performs the first hydroxylation (7-dehydrocholesterol → cholecalciferol occurs in skin, then liver adds 25-OH).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.