vitamin D3 metabolism

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In the skin, sunlight and specifically ultraviolet rays, acts on 7-dehydrocholesterol to form vitamin D3

  • this unhydroxylated form of vitamin D3 is cholecalciferol (also known or calciol)
    • in tandem, vitamin D2 (known as ergocalciferol) and D3 are obtained from the diet. Moderate amounts of bile salts and fat are required for absorption. An alpha-globulin, vitamin D transport protein, binds to the gut- and skin-derived vitamin D3 and transports it to the liver.

Vitamin D3 has several forms:

  • cholecalciferol, (sometimes called calciol) which is an inactive, unhydroxylated form of vitamin D3)
  • calcidiol (also called 25-hydroxyvitamin D3), which is the form measured in the blood to assess vitamin D status
    • in the liver, vitamin D3 is hydroxylated at the 25' position to produce 25-hydroxycholecalciferol (calcidiol). This is then bound to another selective transport protein for transit to the kidneys. Calcidiol is the most abundant form of vitamin D, but is less active than calcitriol.
  • calcitriol (also called 1,25-dihydroxyvitamin D3), which is the active form of D3
    • Within the kidneys, there exist a number of enzymes which hydroxylate calcidiol at various positions. The most important of these seems to be 1-hydroxylase which produces 1,25-dihydroxycholecalciferol (calcitriol). Calcitriol is more potent than the other hydroxylation products in its actions on mineral physiology. Hence, by varying the activity of the 1-hydroxylase enzyme, the ratio of calcitriol to other hydroxylated products can be varied, and so the degree to which calcium and phosphate physiology is affected
      • renal hydroxylation of calcidiol to calcitriol by 1-alpha-hydroxylase is tightly regulated (stimulated by either parathyroid hormone or hypophosphatemia) and serves as the major control point in production of the most active circulating hormone calcitriol (1,25-dihydroxyvitamin D3)

The activity of the 1-hydroxylase enzyme is increased by:

  • hypocalcaemia
  • hypophosphataemia
  • parathyroid hormone
  • growth hormone

Calcidiol within the liver is the main storage form of vitamin D; it has a half life of about 14 days.

Last reviewed 10/2021

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