1,25-Dihydroxycholecalciferol calcium metabolism

Calcitriol (la,25-dihydroxycholecalciferol, vitamin D3, 105) (O Scheme 41) is involved in calcium metabolism. Glycosides of this compound occur in plants [200,201] and also as metabolites in mammal organisms. -Glucopyranosides of 105 linked to the C-1, C-3, or C-25 hydroxyfunctions were tested in vivo (rats) and compared with the aglycon. These glycosides occur as potential sources of vitamin D in plants, e. g., Solanum malacoxylon [200] where... 

Vitamin D (as 1,25-dihydroxycholecalciferol) is involved in calcium metabolism (see Chapter 8). 

This active vitamin D metabolite (1,25 dihydroxycholecalciferol) is an important cofactor for intestinal calcium absorption, which involves calbindins (calcium binding proteins) in the intestine and kidney. Calcitriol is produced in the kidneys by the conversion of 25-hydroxycholecalciferol (calcidiol) and its formation is stimulated by a reduction of plasma calcium and/or phosphate and increased production of parathyroid hormone and prolactin (Figure 6.3). Calcitriol also inhibits the release of calcitonin and, together with PTH, increases the absorption of calcium and phosphate from the gastrointestinal tract and the kidneys. Growth hormone, glucocorticoids, estrogens, testosterone, and the thyroid hormones also influence calcium metabolism. 

Finally, PTH helps increase the absorption of calcium from the gastrointestinal tract. This effect appears to be caused by the interaction between PTH and vitamin D metabolism. PTH increases the conversion of vitamin D to 1,25-dihydroxycholecalciferol (calcitriol).36 Calcitriol directly stimulates calcium absorption from the intestine. 

Q7 Calcium is present in both intracellular fluid (ICF) and ECF, but the concentration in the ECF is twice as high as that in the ICF. Calcium is found in both ionized and bound forms, and Ca2+ homeostasis is mainly controlled by parathyroid hormone, which increases absorption of calcium in the intestine and reabsorption in the nephron. Calcitonin also affects ECF calcium concentration by promoting renal excretion when there is an excess of calcium in the body. The normal kidney filters and reabsorbs most of the filtered calcium however, in renal disease this is reduced and blood calcium decreases. Calcium and phosphate imbalance can occur in patients with renal failure, leading to osteomalacia (defective mineralization of bone). Osteomalacia is mainly due to reduced production of 1,25-dihydroxycholecalciferol, an active form of vitamin D metabolized in the kidney. Deficiency of 1,25-dihydroxycholecalciferol reduces the absorption of calcium salts by the intestine. 

Another important hormone derived from cholesterol is vitamin D. This steroid-like hormone is involved in regulating calcium and phosphorus metabolism. The complete synthesis of vitamin D requires ultraviolet light to convert 7-dehydrocholesterol to previtamin Dj. The reaction scheme is shown in Figure 34-3. The active hormone 1,25-dihydroxycholecalciferol (calcitriol)... 

These two hormones, together with the vitamin calcitriol, regulate calciumhomeostasis and thereby indirectly affect phosphate metabolism. Parathyroid hormone (parathormone PTH) is secreted by the parathyroid glands as a polypeptide of 84 amino acid residues, and its action is to increase plasma calcium via parathyroid hormone receptors in bone, kidney, and a few other tissues. PTH secretion is increased in response to hypocalcemia and hyperphosphatemia conversely, increased plasma calcium suppresses PTH secretion. The renal production of 1,25-dihydroxycholecalciferol is also... 

The metabolic acid-base balance affects the sensitivity of bone to parathyroid hormone (PTH) and the synthesis of 1,25-dihydroxycholecalciferol. Therefore, acknowledging this when balancing the mineral content of the diet can have an effect on the incidence of milk fever. Conditions that promote an alkalotic state (high dietary cations, Na and IC ) reduce the sensitivity of bone to PTH and can limit the release of calcium. Conversely, an acidotic state (high dietary anions, CP and S ) increases the sensitivity to PTH, increases 1,25-dihydroxycholecalciferol production and hence increases the calcium supply. Through these metabolic responses, manipulation of the acid-base balance in the diet of the pre-calving cow has been successful in reducing the incidence of milk fever. 

Dihydroxycholecalciferol is able to act on a number of tissues with columnar epithelial cells, including intestinal mucosa, kidney tubules, the shell gland of birds and probably also various types of bone cell where it may assist the synthesis of osteocalcin (page 161). Its mode of action is very similar to that of steroid hormones (Figure 30.1). In this respect its precursor, vitamin Dj, may be considered to function as a prohormone rather than a vitamin. The ability of 1,25-DHCC and other metabolites of vitamin D3 to act on bone and kidney cells, as well as those of the intestine, means that vitamin D plays a key role in calcium and phosphorus metabolism (Hgure 30.2). 

The metabolically active form of vitamin D. Vitamin D is initially hydroxylated by the liver to 25-hydroxychoIecaIciferol and a further hydroxylation takes place in the kidney to form the dihydroxy compound. 1,25-dihydroxycholecalciferol increases calcium absorption from the intestine and, in conjunction with parathyroid hormone, releases calcium from bone. 

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