Calcium, absorption transport, vitamin

Induction of Calbindin-D In response to calcitriol administration, there is an increase in mRNA synthesis and then in the synthesis of calbindin-D in intestinal mucosal cells, which is correlated with the later and more sustained increase in calcium absorption. In vitamin D-deficient animals, there is no detectable calbindin in the intestinal mucosa, whereas in animals adequately provided with vitamin D, it may account for 1 % to 3% of soluble protein in the cytosol of the colunmar epithelial ceils. Although the rapid response to calcitriol is an increase in the permeability of the brush border membrane to calcium, the induction of calbindin permits intracellular accumulation and transport of calcium. The rapid increase in net calcium transport in tissue from vitamin D-replete animals is presumably dependent on the calbindin that is already present in deficient animals, there can be no increase in calcium transport until sufficient calbindin has accumulated to permit intracellular accumulation, despite the increased permeability of the brush border. 

Minerals and Vitamins. Mineral absorption occurs throughout the small and laige intestines, with the rate of absorption depending on a number of factors—pH, carriers, diet composition, etc. Numerous mechanisms of mineral absorption have been elucidated. Many minerals, for example, iron and sodium, require active transport systems. Others, such as calcium, utilize both carrier proteins and diffusion mechanisms. Moreover, vitamin D is required for calcium absorption, and vitamins C and E favor the absorption of iron. 

Absorption - Calcium is absorbed from the Gl tract by passive diffusion and active transport. Calcium must be in a soluble, ionized form for absorption to occur. Vitamin D is required for calcium absorption and increases the absorptive mechanisms. 

The next stage involves the synthesis of specific calcium-binding proteins, typified by the intestinal CaBP253 discussed in Section 62.1.3.4.5, which probably stimulates the transport of calcium. The role of the protein in vitamin D-dependent absorption of calcium is supported by the good correlation between the concentration of CaBP and the rate of calcium absorption. Under conditions of low calcium or phosphorus diets, chicks and other animals produce more intestinal CaBP to increase the efficiency of uptake of calcium. In general, adaptation to a low calcium diet involves increased synthesis of l,25-(OH)2D3 and the intestinal CaBP. Lowered requirements for calcium in old age are manifested by lower levels of both factors.449,450... 

The relationship of serum calcium and phosphate with rickets was discovered by Howland and Kramer [10]. They found that blood from normal rats could mineralize rachitic rat cartilage, whereas blood from rachitic rats could not. They also provided evidence that a low serum calcium and phosphate status caused rickets. Orr etal. [11] demonstrated that UV irradiation stimulated calcium absorption. This study was largely unappreciated for 30 years until Nicolaysen and Eeg-Larsen [12] and Schachter and Rosen [13] demonstrated evidence for vitamin D-induced intestinal absorption of calcium by an active transport process. 

Not all calcium present in the diet is absorbed by the small intestine and mechanisms are present to ensure only amounts appropriate to body needs are absorbed. These processes are complex and involve the interaction of special transport protein, vitamin D and parathormone. Thus, abnormalities of calcium metabolism may result from many different disease processes. Diseases affecting the bowel may prevent normal absorption, diseases of the parathyroid gland may result in inappropriate levels of parathormone for calcium requirement and a nutritionally inadequate diet may cause vitamin D deficiency with consequent disordered calcium absorption. 

With the isolated perfused duodenum, there is a rapid increase in calcium transport in response to the addition of calcitriol to the perfusion medium. Isolated enterocytes and osteoblasts also show a rapid increase in calcium uptake in response to calcitriol. It is not associated with changes in mRNA or protein synthesis, but seems to be because of recruitment of membrane calcium transport proteins from intracellular vesicles to the cell surface. It is inhibited by the antimicrotubule compound colchicine. It can only be demonstrated in tissues from animals that are adequately supplied with vitamin D in vitamin D-deficient animals, the increase in intestinal calcium absorption occurs only more slowly, together with the induction of calbindin. 

Calcium absorption Calcium in the diet can be absorbed by the intestines by mechanisms that are dependent on and independent of 1,25-dihydroxyvitamin D3. The vitamin D-independent mechanism predominates during the consumption of high-calcium diets. The vitamin D-dependent mechanism is activated and predominates with diets low in calcium. The biochemical mechanisms by which increased levels of l,25-(OH)2D3 in the plasma activate the calcium transport system in the enterocyte are not clear. It is thought that the hormone binds to the cell and travels to the nucleus, where it activates genes coding for components of the calcium transport system. 

PTH also increases intestinal calcium absorption by increasing 1,25 (OH) 2D. PTH is a major trophic factor for renal 25(OH)t>-la-hydroxylase. It increases the conversion of 25(0H)D to the active vitamin D metabolite, l,25(OH)2D. Calcium is absorbed principally in the duodenum, although it can also be absorbed by the distal small bowel and colon. About 30% of a daily calcium intake of 1 g (25 mmo ) is absorbed. Approximately 100 mg (2.5 mmol) of calcium is secreted into gut lumen by intestinal secretion therefore net calcium absorption is 200 mg (5.0 mmol)/day. Calcium is absorbed by passive diffusion and by an active transport system. It is estimated that passive diffusion accounts for absorption of about 10% of ingested calcium per day. Active calcium absorption in the duodenum is under the control of l,25(OH)2D. This vitamin D metabolite increases the intestinal cell synthesis of a calcium-binding protein (CaBP), which enhances the net absorption of ingested calcium. 

The relative contribution of paracellular transport to total calcium absorption shows large variations (between 20 and 100%) according to age (Pansu et al. 1983, Dostal and Toverud 1984, Bronner et al. 1992), the anatomical location, the vitamin D status of the organism, and the luminal calcium concentration (Ireland and Eortran 1973, Nellans 1990, Sheikh etal. 1990). 

It is well known that vitamin D stimulates intestinal calcium absorption. Throu the work of several groups has come the understanding that in response to vitamin D, calcium is transported against an electrochemical potential gradient in the small intestine The most rapid rate of calcium transport is in the duodenum followed by jejunum and ileum Harrison and Harrison have also shown clearly that vitamin D improves intestinal calcium transport even in the colon Physiologically, because of the time during which calcium is subject to absorption, it seems evident that the distal portions of the small intestine are primarily responsible for the bulk of intestinal calcium absorption. 

Vitamin B12 is synthesized in large quantities by the intestinal flora, particularly in ruminants. The exact amount of vitamin B12 required by the normal human is not known. The absorption of vitamin B12 from the gastrointestinal tract is dependent on the presence of a gastric mucoprotein called intrinsic factor. Calcium ions seem to be necessary for the interaction of vitamin B12 with this intrinsic factor. Vitamin B12, which is absorbed only in the ileum, is stored in the liver. There are two transport proteins for vitamin Bj2 transcobalamin I and II, the latter being physiologically more important. Vitamin B12 plays an important role in the metabolism of functional groups with one carbon atom such as the methyl group... 

It is also clear that the introduction of the la-hydroxy function is an absolutely essential metabolic event for calcium absorption. Nephrec-tomized vitamin D-deficient animals show no increase in intestinal calcium transport or bone calcium mobilization in response to physiological doses of vitamin D3 or 25-hydroxyvitamin D3. On the other hand these animals respond efficiently to la,25-dihydroxyvitamin D3. 

Vitamin D. One of the most important factors affecting calcium absorption is an adequate supply of vitamin D, whether from the diet or exposure to ultraviolet radiation of the sun. Vitamin D or its derivative (metabolite), 25-hydroxyc-holecalciferol (25-HCC), increases calcium absorption by inducing synthesis of a calcium-binding protein that facilitates transport of the calcium through the intestinal walls. 

Dj). From the liver 25-OH-D3 is transported to the kidneys where it is converted to l,25-(OH)2-D3, the most active form of vitamin D in increasing calcium absorption, bone calcium mobilization, and increased intestinal phosphate absorption. The active compound 1,25-(OH)2-D3 functions as a hormone, since it is a vital substance made in the body tissues (the kidneys) and transported in the blood to cells within target tissues. This physiological active form of vitamin D3 is then either transported to its various sites of action or converted to its metabolite forms of 24,25-dihydroxycholecalciferol or 1,24,25-trihydroxycholecalciferol (see Fig. V-48). 

The amount of each element required in daily dietary intake varies with the individual bioavailabihty of the mineral nutrient. BioavailabiUty depends both on body need as deterrnined by absorption and excretion patterns of the element and by general solubiUty, and on the absence of substances that may cause formation of iasoluble products, eg, calcium phosphate, Ca2(P0 2- some cases, additional requirements exist either for transport of substances or for uptake or binding. For example, calcium-binding proteias are iavolved ia calcium transport an intrinsic factor is needed for vitamin cobalt,... 

Hydroxy vitamin D pools ia the blood and is transported on DBF to the kidney, where further hydroxylation takes place at C-1 or C-24 ia response to calcium levels. l-Hydroxylation occurs primarily ia the kidney mitochondria and is cataly2ed by a mixed-function monooxygenase with a specific cytochrome P-450 (52,179,180). 1 a- and 24-Hydroxylation of 25-hydroxycholecalciferol has also been shown to take place ia the placenta of pregnant mammals and ia bone cells, as well as ia the epidermis. Low phosphate levels also stimulate 1,25-dihydtoxycholecalciferol production, which ia turn stimulates intestinal calcium as well as phosphoms absorption. It also mobilizes these minerals from bone and decreases their kidney excretion. Together with PTH, calcitriol also stimulates renal reabsorption of the calcium and phosphoms by the proximal tubules (51,141,181—183). 

The active forms of the D vitamins are la,25-dihydroxy-vitamin Dj and 25-hydroxy-vitamin Dj. They are formed by enzymatic hydroxylation in the liver microsomes and then in the kidney mitochondria by a ferredoxin flavoprotein and cytochrome P-450. The 1,25-dihydroxy vitamin is then transported to the bone, intestine, and other target organs (kidneys, parathyroid gland). Consequently, it can be considered a hormone since it is produced in one organ but used elsewhere. It mobilizes calcium and phosphate and also influences the absorption of these ions in the intestine, thus promoting bone mineralization. The hormone is also active in relieving hypoparathyroidism and postmenopausal osteoporosis, which, for example, results in the brittle bones of elderly women. 

Vitamin B12 can be absorbed when present in physiological amounts only if it is first bound to a specific protein—the so-called intrinsic factor—that tightly binds to the vitamin. The complex then passes through the jejunum to the ileum, which contains receptor sites for the vitamin B12/intrinsic factor complex. Calcium ions are required for the reaction between ileal receptors and the intrinsic factor/vitamin B12 complex. The reaction is inhibited by EDTA and reduced by a pH below 5.4. The vitamin appears to be separated from intrinsic factor at the ileal receptor sites and is then bound to another protein carrier, transcobalamin II, which transports the vitamin and permits its uptake by a number of tissues. The subject has been well reviewed by Jacob and her colleagues (Jl). Removal of 60 cm of ileum may impair vitamin B12 absorption and with the loss of 180 cm absorption is almost always affected. 

Tissues contain two types of receptors for 1,25-dihydroxyvitamin D a classic steroid hormone nuclear receptor and a putative membrane receptor. 1,25-Dihydroxyvitamin D interacts with the nuclear receptor to form a receptor-ligand complex (Fig. 30-4). This complex then interacts with other nuclear proteins, such as the retinoic acid receptor (RXR) to form a functional transcription complex. The main effect of this transcription complex is to alter the amount of mRNAs coding for selected proteins such as cal-bindin, the calcium transport protein in the intestine, and the vitamin D receptor. In concert with PTH, 1,25-dihydroxyvitamin D acts to mobilize calcium from bone.As a consequence, serum calcium and phosphate homeostasis is maintained by a combination of 1,25-dihydroxyvitamin D stimulation of intestinal absorption and bone turnover. 

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