Influence calcium metabolism

In addition to its classical role as regulator of calcium homeostasis, 1,25-dihydroxy vitamin D3 (calcitriol) displays immunosuppressive properties. Inhibition of T-lymphocyte proliferation seems to be mediated via regulation of CD80/86 costimulatory molecule expression on APCs. For clinical use as immunosuppressant, however, analogues of vitamin D3 that do not influence calcium metabolism are needed. 

Longer lasting control of mineral metabolism is achieved by steroid hormones elaborated by the adrenal cortex and by synthetic analogues. Besides their actions on gluconeogenesis, glycogen deposition, protein metabolism and sexual characteristics, the corticosteriods influence calcium metabolism and the control of water and electrolyte equilibria, so that profound changes accompany their administration. 

Long-term anticonvulsive therapy with diphenylhydantoin or phenobarbital is known to cause osteomalacia by influencing calcium metabolism (24,25). Alteration in the metabolism of vitamin D, presumably secondary to induction of hepatic microsomal enzymes, leads to the calcium and bone abnormalities (26). Patients on anticonvulsive therapy with phenytoin exhibit a decrease in serum 25-hydroxyvitamin D (27). Adequate dietary amounts of vitamin precursors or microsomal enzyme stimulators might prevent these effects of long-term therapy. 

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. 

There is some evidence, mostly from animal studies, to suggest that high dietary levels of phosphorus, especially if dietary levels of calcium are low, may adversely affect bone mass and calcium metabolism (Greger and Krystofiak 1982). However, in humans there is little direct evidence to indicate that large variations in dietary phosphorus or in the Ca P ratio have any significant influence on calcium utilization or balance (Heaney et al. 1982). Some preliminary findings, however, suggest that the form of phosphorus may influence calcium absorption (Zemel et al. 1982). Hexametaphosphate, as compared with orthophos-... 

It has been further reported that not only the calcium metabolism but also other minerals and other aspects of mineral status may be influenced by CPPs. Ait-Oukhatar et al. (1997) found that in young iron-deficient rats, CPP-bound iron had a positive effect on some parameters of iron status and metabolism, such as mean cell volume, haemoglobulin and haematocrit, and a negative effect on some parameters, such as urine iron. Other parameters,... 

Vitamin D, (1) is an essential factor for the life of animals and man. It is formed in the skin under the influence of UV light from provitamin D3 (2) and is one of the most important regulators of calcium metabolism. For instance, children lacking vitamin D develop rickets and adults suffer from osteoporosis. 

Husdan H, Rapoport A, Locke S. Influence of posture on the serum concentration of calcium. Metabolism 1973 22 787-97. 

It has been known for 20 years that secretion of granule bound materials generally requires the presence of calcium in the medium (9). If calcium is omitted from the fluid perfusing a secretory tissue, evoked secretion is abolished or at least diminished. However, not all secretory cells handle calcium in the same way and more recent work emphasizes the role of calcium in membrane stabilization, the influence of magnesium ion on calcium mediated events, and the effect of stimulation frequency on calcium metabolism. 

The influence of parathormone is only one of the numerous examples of the intercorrelations of citrate and calcium metabolisms (Cl, H8, M25). Vitamin D is also correlated with citrate (Fll, H8, Hll, H12). The urinary citrate increases, for instance, after administration of this vitamin, which seems to affect the metabolism of citrate directly and not through prior modifications in calcium metabolism (H8). It is interesting, from that point of view, to quote De Luca et al. (D9, DIO, Dll), who have shown that vitamin D diminishes the conversion of citrate to a-ketoglutarate in rat kidney (but not liver) homogenates and mitochondria it is possible that this vitamin is connected with the synthesis of phospho- or pyrophosphocitrate (M22). 

Calcium-regulating sterols control the resorption of calcium ions into the gastro-intestinal tract, and influence bone metabolism. Vitamin D3 (chole-calciferol), generated by photolysis of 7-dehydrocholesterol, is its most prominent member. 

Parathormone, parathyrin a hormone produced by the parathyroid gland, which influences the metabolism of calcium and phosphate. It is a single chain proteohormone with 84 amino acid residues of known primary structure [R.T. Sauer etal. Biochemistry 13 (1974), 1994-1999]. M, 9,402 (porcine). P. influences the cells that degrade bone (osteoclasts) by activation of membrane-bound adenylate cyelase and by increasing the entry of Ca into these cells. The resulting mobilization of Ca causes an increase in blood ealcium. This is necessarily accompanied by the release of free phosphate which is excreted via the kidneys. Thus P. favors phosphate secretion in the distal part of the kidney tubule, and inhibits phosphate resorption in the proximal tubule. P. promotes calcium absorption by the intestine. The action of P. is therefore opposite to that of Calcitonin (see). P. is degraded by the liver, and some is excreted in the urine. Absence of P. leads to a decrease of blood calcium, accompanied by neuromuscular overexcitability (tetany). 

The metabolism of phosphate is closely linked to that c calcium. The factors which regulate calcium metabolism als influence phosphate metabolism. Among these factors are ... 

Little is known about the biochemical mechanism of vitamin D action. It promotes the absorption of Ca++-ions in the gastro-intestinal tract and influences the metabolism of bone tissue. Deficiency of vitamin D results in the clinical syndrome rachitis (also in animal experiments), characterized by a softenii (inadequate calcification) of the bones. Excessive administration of vitamin D produces a hyper-vitaminosis, during which calcium is again mobilized out of the bone structure this hypervitaminosis resembles the action of the parathyroid hormone. 

Susceptibility to lead toxicity is influenced by dietary levels of calcium, iron, phosphorus, vitamins A and D, dietary protein, and alcohol (Calabrese 1978). Low dietary ingestion of calcium or iron increased the predisposition to lead toxicity in animals (Barton et al. 1978a Carpenter 1982 Hashmi et al. 1989a Six and Goyer 1972 Waxman and Rabinowitz 1966). Iron deficiency combined with lead exposure acts synergistically to impair heme synthesis and cell metabolism (Waxman and Rabinowitz 1966). 

Calcium and phosphorus metabolism Calcium and phosphorus metabolism is influenced by estrogens use caution in patients with metabolic bone diseases associated with hypercalcemia or in renal insufficiency. 

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