Hepatic 25-hydroxylation
Sensor / first step · CYP2R1 Substrate-driven
The liver adds the first hydroxyl group at carbon 25, mainly through CYP2R1. The step is essentially unregulated and driven by substrate supply, so its product 25-hydroxyvitamin D simply mirrors intake and sun exposure. That is why it, and not calcitriol, is the measure of vitamin D status.
Traced from the start
- Cholecalciferol from skin and diet
- Hepatic 25-hydroxylation
Detail
- Enzymes
- CYP2R1 is the principal microsomal 25-hydroxylase, with a contribution from mitochondrial CYP27A1
- Regulation
- Little negative feedback: output tracks supply, which is what makes 25(OH)D a status marker
- Product handling
- 25(OH)D circulates on vitamin D-binding protein with a half-life of 2-3 weeks; the filtered complex is retrieved by megalin and cubilin in the proximal tubule for the second hydroxylation
When it goes wrong
Enzyme-inducing drugs: phenytoin, carbamazepine, phenobarbitone, rifampicin
Accelerated vitamin D catabolism with low 25(OH)D, secondary hyperparathyroidism and osteomalacia on long-term therapy
Advanced cirrhosis or chronic cholestasis
Impaired 25-hydroxylation together with malabsorption of a fat-soluble vitamin: hepatic osteodystrophy
Practise this structure
1 question in the bank tagged Vitamin D.