Healthy Beauty · Health & Balance · Sex & Relationships · Oral Care; View All Both calcium and phosphorus are found naturally in dairy products, but most can bind up to mg of phosphorus -- making it unavailable to the body. calcium carbonate, may block most of the absorption of phosphorus. Read our resource on Calcium & Phosphorus Metabolism. The importance of both Ca2+ and phosphorus in the body is reflected in the exquisite .. The relationships between VitD, PTH, and FGF are complex and perhaps not intuitive. Body Distribution of Calcium and Phosphate. There are Calcium in blood and extracellular fluid: Roughly half of the calcium in blood is bound to proteins.
This induces internalization with apparent complex dissociation.
Calcium and Phosphate Homeostasis
It does so by up-regulating the activity of hydroxylase, an enzyme that replaces the hydroxide at the 1 position with a hydroxide at position 24, inactivating the vitamin. It does play a role in immunity, reproduction, and phosphate metabolism, and it does have a complex relationship with other crucial hormones associated with bone metabolism. But, in summary, its target is intestinal. During winter, or under sunless conditions, either nutritional supplements, fatty fish, or also fortified milk are required to supply needed vitamin D3.
Dietary vitamin D3 is absorbed by the gut, transported to the liver by chylomicrons, and either stored in fat or converted to 25 OH vitamin D3.
Nutritional supplements may contain either vitamin D2 or vitamin D3. Both are convertible into active 1,25 OH 2 vitamin D.
It must also be successfully incorporated into bone mineral, a process strongly impacted by vitamin K. PTH is produced by the dark Chief cells of the parathyroid. PTH production may also be regulated by Pi. When released, PTH would seem to exist in a bewildering number of isoforms. It is initially synthesized as a amino acid aa prepropeptide that contains a 25 aa signal sequence and a six aa N-terminal pro-segment. The C-terminal 84 aa make up the mature, circulating form of PTH.
There are fragments that start at aa position 4, 7, 8, 10, 15, 34 35, 37, 41, and 43, and perhaps more differing at the C-terminus. It has yet to be characterized. PTH, by definition, is a normo-calcemic hormone. It has an indirect, but important effect on phosphorus. As with other members, FGF shows a typical beta-trefoil structure. This places it in the small FGF subfamily. This mature form, however, is bio-inactive; it appears that the C-terminal pro-segment is essential for bioactivity.
It also induces 1 alpha-hydroxylase activity in kidney to create active VitD. VitD does two important things. With increased VitD activity, however, phosphorus is now in excess.
PTH, in the short term, can influence Pi excretion in a manner identical to that of FGF; that is, promote excretion rather than reabsorption. What is needed longer-term is an additional phosphatonin that will bring phosphorus levels back to normal. It would appear that VitD induces its expression. High phosphorus diets in renally uncompromised individuals does lead to increased excretion, but without a change in FGF In mice, dietary phosphorus is also reported to affect FGF synthesis.
Thus, the system may show some species specificity. Calcitonin has a potent inhibitory action on osteoclasts mediated by its GPCR, termed the calcitonin R. The molecule seems to have an ontogenic component to it, as it is highly active in the young of species and loses its potency with age. In adult humans, it may act as a stress-related molecule. Soluble Frizzled-related Protein-4 sFRP-4 sFRP-4 is a member of a small family of secreted proteins that structurally resemble the extracellular domain of the frizzled family of receptors.
In rat, the molecule is highly spliced, with variants occurring at the C-terminus. Although highly conjectural, there are at least three possible mechanisms of action. First, FGF, when present as a full-length molecule, shows phosphatonin activity.
When cleaved into mature N- and C-termini, it loses its activity.
The Balance of Calcium & Phosphorus
It should be noted that furin-type convertases have also been reported to cleave FGF Since osteoblasts initiate bone formation, a reduction in osteoblast number would translate into a reduction in mineralization rate that would be accompanied by a reduced need for phosphate.
This would translate into a reduction in kidney Pi resorption due to reduced demand. MEPE is synthesized by osteoblasts and osteocytes, particularly during mineralization. The regulation of mineralization may be the principal function for MEPE or its cleavage product. The phosphatonin effect, while material, may be complementary except under unregulated conditions. In particular, both paracellular and transcellular processes are found to exist.
Transcellular hormone-sensitive resorption occurs in the distal segments. Passive uptake in the proximal and straight tubules presumably involves paracellin-1 and the same ion transport mechanisms that exist in enterocytes.
Calcium & Phosphorus Metabolism: R&D Systems
This receptor is found on the basolateral membrane. More study needs to be done on this point. Each day, approximately mg of Pi enter the glomerular filtrate, while mg of Pi are recaptured. View Larger Image Figure 5. In the proximal tubule, Pi must be actively transported from the urine into the cell against a very strong electrochemical gradient.
Type 1 family members are NPT1, 3, and 4. The type 3 family has two members, Pit1 and 2. Part of their function is to maintain needed intracellular phosphate. It is an 8 transmembrane domain protein that exhibits complex regulation. The identity of the basolateral transporter is unknown. With respect to molecules that promote NPT2a activity, VitD is known to upregulate its expression, likely through a transcriptional mechanism.
VitD response elements exist in the NPT2a promoter. It is a secreted phosphoprotein that is made by collecting duct epithelium. This has yet to be demonstrated. This reduces phosphate uptake and generates phosphaturia high urinary phosphate.
The effects of sFRP-4 are not well characterized, but have been suggested to involve NPT2a removal from the luminal membrane. MEPE is perhaps the least well understood phosphatonin. It occurs during development, disease, and normal bone homeostasis. Three types of bone formation are described: It is suggested that they are either pre-existing or migrate to sites of osteogenesis, or they form from resident precursors under the influence of various osteoblast inducers. It is suggested by many to be the only collagen in bone.
BSP-1 is an 85 kDa, sulfated glycoprotein that shows an affinity for hydroxyapatite. It is one of the many vitamin-dependent proteins associated with bone.
Vitamin C is necessary for hydroxylation at Pro9, VitD initiates gene expression, and vitamin K is a cofactor for vitamin K-dependent carboxylase. The latter enzyme adds a gamma-carboxyl residue to the molecule. Osteocalcin has been described as both a promoter and inhibitor of mineralization. Stimulating net resorption of bone mineral releases calcium and phosphate into blood, and suppressing this effect allows calcium to be deposited in bone.
The kidney is critcally important in calcium homeostasis. Under normal blood calcium concentrations, almost all of the calcium that enters glomerular filtrate is reabsorbed from the tubular system back into blood, which preserves blood calcium levels.
If tubular reabsorption of calcium decreases, calcium is lost by excretion into urine. Hormonal Control Systems Maintaining normal blood calcium and phosphorus concentrations is managed through the concerted action of three hormones that control fluxes of calcium in and out of blood and extracellular fluid: Parathyroid hormone serves to increase blood concentrations of calcium.
Mechanistically, parathyroid hormone preserves blood calcium by several major effects: Stimulates production of the biologically-active form of vitamin D within the kidney. Facilitates mobilization of calcium and phosphate from bone. To prevent detrimental increases in phosphate, parathyroid hormone also has a potent effect on the kidney to eliminate phosphate phosphaturic effect.
Maximizes tubular reabsorption of calcium within the kidney. This activity results in minimal losses of calcium in urine. Vitamin D acts also to increase blood concentrations of calcium. It is generated through the activity of parathyroid hormone within the kidney.
Far and away the most important effect of vitamin D is to facilitate absorption of calcium from the small intestine.
In concert with parathyroid hormone, vitamin D also enhances fluxes of calcium out of bone. Calcitonin is a hormone that functions to reduce blood calcium levels. It is secreted in response to hypercalcemia and has at least two effects: Suppression of renal tubular reabsorption of calcium. In other words, calcitonin enhances excretion of calcium into urine. Inhibition of bone resorption, which would minimize fluxes of calcium from bone into blood.
Although calcitonin has significant calcium-lowing effects in some species, it appears to have a minimal influence on blood calcium levels in humans. A useful way of looking at how hormones affect tissues to preserve calcium homeostasis is to examine the effects of calcium deprivation and calcium loading.