| page 220 |  | | page 221 |
| Figure 16.8 Formation and hydroxylation of vitamin D3 (cholecalciferol) |
| page 221 | | | page 222 |
Vitamin D3 (cholecalciferol) is also derived from cholesterol and plays a very important role in calcium metabolism. Small
amounts of the fat-soluble vitamins D occur in food, (e.g. fish liver oil, egg yolk), but the majority of cholecalciferol is manufactured in the Malpighian layer of the epidermis of the skin (Fig 16.8). Cholesterol is converted to 7-dehydrocholesterol, which acts as the substrate for a unique nonenzymatic photolysis reaction in which ultraviolet rays from sunlight mediate the opening of the B-ring of cholesterol so destroying the steroid nucleus (see Chapter 24). The rate of this reaction is inversely related to the amount of pigment in the skin and directly related to the amount of sunlight exposure. Cholecalciferol is transported in plasma bound to a specific vitamin D-binding protein. In the liver it undergoes hydroxylation at C-25 to produce 25-hydroxycholecalciferol (calcidiol). This step, which is not regulated, is catalyzed by a cytochrome P450 mono-oxygenase in the endo-plasmic reticulum. 25-Hydroxycholecalciferol is then transported in plasma to the kidney, bound to the same specific protein. Production of the potent hormone, 1,25-dihydroxycholecalciferol (calcitriol ), requires the contribution of a 1α-hydroxylase (yet another P450 containing mono-oxygenase) located within the mitochondria of the renal proximal tubule. The actions of 1,25-dihydroxycholecalciferol are discussed in Chapter 24.
|
|
