Intestines calcium uptake

CalcitrioTs effects on bone are predominantly mediated by its actions to stimulate intestinal calcium uptake, although large doses can directly stimulate bone resorption. Similarly, there are direct effects of calcitriol to stimulate CcP reahsorption in the distal tubule. The physiological impact of these effects is unknown. 

Larsson D., Bjomsson B.T. and Sundell K. 1995. Physiological concentrations of 24,25-dihy-droxyvitamin D3 rapidly decrease the in vitro intestinal calcium uptake in the Atlantic cod, Gadus morhua. Gen. Comp. Endocrinol. 100(2) 211-5. 

INTESTINE (Duodemjm) increase calcium uptake from intestine... 

Vitamin D3, also called cholecalciferol, is normally formed in the skin from 7-dehydrocholesterol in a photochemical reaction driven by the UV component of sunlight (Fig. 10-20). Vitamin D3 is not itself biologically active, but it is converted by enzymes in the liver and kidney to 1,25-dihydroxycholecalciferol, a hormone that regulates calcium uptake in the intestine and calcium levels in kidney and bone. Deficiency of vitamin D... 

Effect of vitamin D on the intestine 1,25-diOH D3 stimulates intestinal absorption of calcium and phosphate. 1,25-diOH D3 enters the intestinal cell and binds to a cytosolic receptor. The 1,25-diOH D3-receptor complex then moves to the nucleus where it selectively interacts with the cellular DNA. As a result, calcium uptake is enhanced by an increased synthesis of a specific calcium-binding protein. Thus, the mechanism of action of 1,25-diOH D3 is typical of steroid hormones (see p. 238). 

Vitamin D3 is a precursor of the hormone 1,25-dihy-droxyvitamin D3. Vitamin D3 is essential for normal calcium and phosphorus metabolism. It is formed from 7-dehydrocholesterol by ultraviolet photolysis in the skin. Insufficient exposure to sunlight and absence of vitamin D3 in the diet leads to rickets, a condition characterized by weak, malformed bones. Vitamin D3 is inactive, but it is converted into an active compound by two hydroxylation reactions that occur in different organs. The first hydroxylation occurs in the liver, which produces 25-hydroxyvita-min D3, abbreviated 25(OH)D3 the second hydroxylation occurs in the kidney and gives rise to the active product 1,25-dihydroxy vitamin D3 24,25 (OH)2D3 (fig. 24.13). The hydroxylation at position 1 that occurs in the kidney is stimulated by parathyroid hormone (PTH), which is secreted from the parathyroid gland in response to low circulating levels of calcium. In the presence of adequate calcium, 25(OH)D3 is converted into an inactive metabolite, 24,25 (OH)2D3. The active derivative of vitamin D3 is considered a hormone because it is transported from the kidneys to target cells, where it binds to nuclear receptors that are analogous to those of typical steroid hormones. l,25(OH)2D3 stimulates calcium transport by intestinal cells and increases calcium uptake by osteoblasts (precursors of bone cells). 

Although bone is not considered a major calcium sensing organ in humans, the cells of bone tissue control over 99% of the human body s calcium content. The principal calcium sensors that regulate bone calcium uptake and release are in the parathyroid glands. Bone function is also modified by vitamin D and by calcium transport in the kidney and intestine. These indirect mechanisms of controlling bone calcium metabolism are beyond the scope of our considerations here. In spite of processing... 

Cholecalciferol is hydroxylated at three positions in the carbon skeleton, 1, 24, and 25. In the liver, cholecalciferol is hydroxylated to 25-hydroxycholecalciferol. Further hydroxylation reactions occur in the kidney, resulting in the formation of three new metabolites. These are 1,25-dihydroxycholecalciferol 24,25-dihydroxycholecalciferol and 1,24,25-trihydroxycholecalciferol. 1,25-Dihydroxy- and 1,24,25-trihydroxycholecalciferol are active hormones involved in calcium uptake from the intestine. 

Q13 Osteomalacia and osteoporosis are complications of celiac disease. The mineral in bone is mainly calcium phosphate a supply of calcium is therefore needed for bone growth and replacement. Calcium is absorbed by active mechanisms in the duodenum and jejunum, facilitated by a metabolite of vitamin D. It is also passively absorbed in the ileum and specific calcium binding proteins are present in the intestinal epithelial cells. Loss of absorptive cells and calcium binding proteins markedly decreases calcium uptake and limits its availability for bone growth and repair. 

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. 

Early studies showed that, after the administration of [ H]cholecalciferol or ergocalciferol to vitamin D-deficient animals, there is marked accumulation of [ H] calcitriol in the nuclei of intestinal mucosal cells. Physiological doses of vitamin D cause an increase in the intestinal absorption of calcium in deficient animals the response is faster after the administration of calcidiol and faster stUl after calcitriol. There are two separate responses of intestinal mucosal cells to calcitriol a rapid increase in calcium uptake that is due to recruitment of calcium transporters to the cell surface (Section 3.3.2) and a later response from the induction of a calcium binding protein, calbindin-D. 

When there is adequate sunlight, no dietary source of the vitamin is required. Indeed, an argument can be made that the calciferols are not normal components of the diet. In the United States, it is added to milk, other dairy products, and dairy substitutes. Fish is about the only natural food source. Cholecal-ciferol is produced in the body from endogenously synthesized 7-dehydrocholecalciferol (Fig. 8.10). Consistent with a hormone model, excess amounts of cholecalcdferol can result in excess calcium uptake from the intestinal tract, leading to calcification of soft tissues. 

Intestinal calcium absorption is influenced by dietary factors. Lactose and other sugars increase water absorption, thereby enhancing passive calcium uptake. The effect of lactose is especially valuable because of its presence in milk, a major source of calcium. Lactose also increases absorption of other metal ions. This effect may contribute to the incidence of lead poisoning (plumbism) among young inner-city children exposed to high dietary levels of both lead and lactose. 

H)2D increases reabsorption of phosphate in the kidney and intestinal absorption of phosphate. In the intestine, phosphate is absorbed as a counterion with Ca + and also by a calcium-independent route. Phosphate flux through both pathways is increased by l,25-(OH)2D but more slowly than calcium transport. The calcium-independent pathway may involve alkaline phosphatase, the activity of which is increased by l,25-(OH)2D. In rat intestine in vitro, phosphate transport is greatest in the jejunum and least in the ileum, whereas calcium uptake is highest in the duodenum. 

PTH also acts to increase absorption of calcium ion by the small intestine. It does this indirectly by promoting the formation of active vitamin D in the kidney. PTH acts on the final, rate-limiting step in vitamin D synthesis, the formation of 1,25-dihydroxycholecalciferol in the kidney. If PTH is low, formation of the inactive derivative, 24,25-dihydroxycholecalciferol, is stimulated instead. Vitamin D acts on intracellular receptors in the small intestine to increase transcription of genes encoding calcium uptake systems, to up-regulate their expression. 

B. Hyperparathyroidism is the likely cause of all of the patient s symptoms. Increased parathyroid hormone leads to bone demineralization, increased calcium uptake from the intestine, increased blood levels of calcium, decreased calcium ion excretion by the kidney, and increased phosphate excretion in the urine. Increased blood calcium levels caused renal stones, while bone demineralization progressed to osteopenia. The patient s intake of calcium and vitamin D are not excessive. Calcitonin acts to decrease bone demineralization. Muscle weakness and depression reflect the widespread role of calcium ion in many physiologic processes. 

The calcium-transport system is another potential source of binding proteins. Transport into mitochondria, across plasma membranes and through the intestinal mucosa and the renal tubule may be the function of distinct transport systems, each of which may be the source of binding proteins. The possibility of isolating bacterial mutants deficient both in calcium uptake and in calcium-binding proteins offers an interesting approach to the role of binding proteins in calcium transport. 

Some drugs, for example anticonvulsants phenytoin, phenobarbital and corticosteroids can lead to osteomalacia and rickets by depressing vitamin D dependent calcium uptake in the intestine. 

The activities of la,25(OH)2D4 on a calcium transport and bone mobilization in vitamin D deficient SD rats were less than (about 1/2) those of la,25(OH)2D3. This is well understood by stronger affinity of la,25(OH)2D4 for DBP than that of la,25(OH)2D3 because of the decreased availability for target cells (decreased uptakes into the cells)[43,44], The hypercalcemic activities of 24-epi-la,25(OH)2D2 and la,25(OH)2D7 were negligible as compared with that of la,25(OH)2D3. Their effects on intestinal calcium transport was significantly smaller than that of la,25(OH)2D3 and it is required 10 fold more of these compounds to produce a similar activity to la,25(OH)2D3 [35]. 

The several forms of vitamin D play a major role in the regulation of calcium and phosphorus metabolism. One of the most important of these compounds, vitamin D3 (cholecalciferol), is formed from cholesterol by the action of ultraviolet radiation from the Sun. Vitamin Dg is further processed in the body to form hydroxylated derivatives, which are the metabolically active form of this vitamin (Figure 8.30). The presence of vitamin Dg leads to increased synthesis of a Ga -binding protein, which increases the absorption of dietary calcium in the intestines. This process results in calcium uptake by the bones. 

Intracellular calcitriol receptors are widespread in the body. They are found, for example, in the small intestine, the kidneys, the bones, and the parathyroid gland. Calcitriol binds to these receptors and induces at the DNA level the transcription of hormone-sensitive genes. It influences cell differentiation and proliferation, stimulates an increased uptake of calcium ions from the intestine through enhanced formation of calcium-binding proteins, and also controls the release of calcium from the bones. [91] Since the counter-ion of the calcium is mostly phosphate, calcitriol raises consequently the phosphate level in blood as well. While the release of calcium from the bones appears counterproductive, this effect is however over-compensated by the increased intestinal calcium resorption, resulting in an elevated serum concentration. 

The K. is the site of synthesis of Erythropoietin (see) and Renin (see). Renin is synthesized in the juxtaglomerular cells it releases Angiotensin (see), which in turn stimulates the release of aldosterone by the adrenal cortex. 25-Hydroxycholecalciferol (produced in the liver from vitamin D3 or cholecalci-ferol) is converted by the kidney into 1,25-dihydroxy-cholecalciferol, which promotes calcium uptake by the intestine and calcium mobilization in bone. 

S. Freund, T., and F. Bronner Stimulation in vitro by 1,25-Dihydroxyvitamin D3 of Intestinal Cell Calcium Uptake and Calcium Binding Protein. Science 190, 1300 (1975). 

Little is known of the chain of molecular events that brings the calcium from the luminal to the serosal side of the intestinal cells. Certainly calcium must enter the luminal and be excreted at the serosal side. Studies in which metabolic inhibitors were used have suggested that calcium uptake may involve an energy dependent accumulation of calcium in mitochondria and that calcium efflux at the serosal site against the chemical and electrical potential gradients is an active transport process. 

A number of factors have been suspected in calcium transport ionic exchange, a calcium sensitive ATPase, a calcium binding protein, vitamin D, parathormone, cortisone. Calcium uptake is depressed by sodium and enhanced if one-third of the sodium is replaced by mannitol. It appears that sodium is not required for calcium uptake or transepithelial transfer. The intestinal brush border contains a calcium-sensitive magnesium dependent ATPase. In contrast to the K, Na" ATPase, the enzyme is not inhibited by ouabain. Vitamin D induces its appearance. The exact role of the ATPase remains unresolved. 

The claimed health-promoting activities exerted by bifidobacteria are numerous, and include establishment of a healthy microbiota in preterm infants, cholesterol reduction, lactose intolerance, prevention of infectious diarrhea, prevention of cancer, protection against infectious diseases, modulation of mucosal barrier function, amino acid and vitamin production, inhibition of nitrate reduction, stimulation of calcium uptake by enterocytes, short-chain fatty acid production, stimulation of intestinal epithelia through induction of anti-inflammatory c5dokine interleukin (IL)-IO and junctional adhesion molecules. ... 

Khanal, R.C., Peters, T.M., Smith, N.M., Nemere, I. 2008. Membrane receptor-initiated signaling in l,25(OH)2D3-stimulated calcium uptake in intestinal epithelial cells. J. Cell. Biochem. 105 1109-1116. 

Nemere, I., Garbi, N., Hammerling, G.J., and Khanal, R.C. 2010. Intestinal cell calcium uptake and the targeted knockout of the 1,25D3-MARRS (membrane-associated, rapid response steroid-binding) receptor/PDIA3/Erp55./. Biol. Chem. 285(41) 31859-66. 

Nemere, I. and Szego, C.M. 1981a. Early actions of parathyroid hormone and 1,25-dihy-droxycholecalciferol on isolated epithelial cells from rat intestine I. Limited lysosomal enzyme release and calcium uptake. Endocrinology 108(4) 1450-62. 

Sterling T.M., and Nemere 1. 2007. Calcium uptake and membrane trafficking in response to PTH or 25(0H)D3 in polarized intestinal epithehal cells. Steroids 72 151-5. 

Figure 15.13 The roles of different tissues in production of the active form of vitamin D. Two major effects of vitamin D are presented release of calcium from bone and uptake of calcium from the intestine.

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