Physiology · Calcium Homeostasis and Bone Metabolism

Cholecalciferol formed in the skin must undergo two successive hydroxylations to become fully active. Where does the first hydroxylation, forming 25-hydroxyvitamin D, take place?

  • A Kidney proximal tubule
  • B Small intestine
  • C Skin keratinocytes
  • D Liver
Correct answer: D. Liver

Explanation

Vitamin B₃ from the skin or diet is transported bound to vitamin B-binding protein and undergoes 25-hydroxylation in the liver by the enzyme CYP2R1, producing 25-hydroxyvitamin B, the major circulating store. The second, tightly regulated 1-alpha-hydroxylation then occurs in the renal proximal tubule. Because the first step is hepatic, advanced liver disease reduces circulating 25-hydroxyvitamin B levels.

Reference: Ganong's Review of Medical Physiology, 26th ed.

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