Regulation of calcium and phosphorus metabolism.

the balance of calcium and phosphorus metabolism in the body is mainly regulated by thyroxine, 1,25-(OH) 2D3 and calcitonin.

(i) parathormone (PTH)

1. Synthesis and secretion

A single-stranded < a href> >peptide hormone, mature PTH contains 84amino acids residues, molecular weight of about 9500. It is the main hormone that maintains a constant level of calcium in the blood.

PTH synthesis follows a typical in-cell < a href""" > of polypeptide synthesispathways. The first synthesis is the pre-thyroid hormone pro PTH, which contains 115 amino acids.

the signal peptides of 25 amino acids at the N end are removed from the coarse end of the internal network, degraded to pro PTH, containing 90 amino acid residues, with no physiological activity. Pro PTH further cut out 6 amino acid residues at the N end in the Golki body and assembled them into mature, biologically active PTH secretion particles.

exactly the same biological activity. The main subject binding point is 1-6, and its removal will result in the loss of all biological activity. C-unending pieces are not biologically active, but determine the immunogenicity of PTH, which should be noted when PTH radiation immunometric determination.

PTH in the blood for only a few minutes, and the storage of PTH in thyroid cells is limited. As a result, secretion cells continue to synthesize and secrete PTH. Blood calcium is the main factor that regulates PTH levels, and blood calcium not only regulates the secretion of PTH, but also affects the degradation of PTH.

effect of low blood calcium (within a few seconds) is to stimulate the release of stored PTH, while the continuous effect is mainly to inhibit the degradation rate of PTH. The latter is the main mechanism for regulating the PTH level of exostemia. When the level of blood Ca2 plus decreases, the rate of PTH degradation in the body slows down and the level of PTH in blood increases.

addition, 1,25-(OH)2D3 is also associated with PTH secretion, and when blood 1,25-(OH)2D3 increases, PTH secretion decreases and calcitonin promotes PTH secretion. On the one hand, by reducing the indirect effect of calcium in the blood, on the other hand, it can directly stimulate the secretion of PTH in the thyroid gland.

(ii) physiological effect of PTH is the target organ is the kidneys, bones and small intestine. PTH is used in the target cell membrane

adenosine cyclase system to increase the levels of cAMP and PPi in the plasma. The former promotes the transmission of Ca2 plus to cytotherapils in mitochondrial bodies, while the latter acts on the outer side of the cell membrane, increasing the inlet of Ca2 plus into the cell, so that the concentration of cell pulp Ca2 plus increases, so that the "calcium pump" on the cell membrane is activated, the Ca2 plus is transported to the extracellular fluid in large quantities. The overall effect of PTH is to increase blood calcium.

1. The effect on

PTH has the dual effect of promoting bone and bone dissolution. Experimental studies have shown that small doses of PTH can promote bone-forming effects, while large doses can promote bone-soluble effects. PTH stimulates bone cells to secrete insulin samplesgrowth factor I (IGF), thereby promoting the synthesis of bone collagen and substrings, which is good for bone-forming.

clinical use of this role, osteoporosis patients with continuous use of small doses of PTH treatment, achieved good results. On the other hand, PTH can increase the number and activity of bone >-breaking cells in bone , bone-breaking cells secrete various hydrolyzed enzymes, and produce a large number of acidic substances such as lactic acid and citric acid, so that bone substrates and bone salts dissolve, releasing calcium and phosphorus to extracellular fluids. But PTH only causes an increase in blood calcium, while blood phosphorus decreases because of the effect of PTH on the kidneys.

2. Effect on the kidneys

The effect of PTH on the kidneys was the earliest, mainly to increase the re-absorption of Ca2 plus by the renal near-curvature tube, to reduce the renal phosphorus excretion threshold and to inhibit the re-absorption of phosphorus by the renal tube. Its conception is through the cell membrane acceptor and camp system, change the cell membrane to Ca2 plus permeability, so that Ca2 plus internal flow increased, intracellular plasma Ca2 plus concentration increased, reduce the cavity face Na plus permeability, Na plus exchange decreased, Na plus, HCO3-discharge increased, phosphorus discharge also increased accordingly.

same time, through the "calcium pump" of the plasma membrane surface so that Ca2 plus into the blood, the result of which makes the urine calcium reduction, urine phosphorus increase, and ultimately make the blood calcium rise, blood phosphorus decreased.

3. Effect on the small intestine

The effect of PTH on calcium and phosphorus absorption in the small intestine is generally believed to play an indirect role by activating the kidney 1 alpha-hydroxylase to promote the synthesis of 1,25-(OH) 2D3, which occurs more slowly.

(ii) 1,25-(OH)2D3

1. Synthesis and regulation

1,25-(OH)2D3 is a hormone produced byvitaminD3 in the body, which is the main physiological activity form of vitamin D3 in the body. Vitamin D3 and its presumors produce 1,25-(OH)2D3 in the skin, liver, kidneys, etc. after a series of enzyme-promoting reactions, and then transported by blood to the small intestine, bone and kidneys and other target organs to play a physiological role.

: Cholesterol metabolite intermediates are more distributed in the skin. Under ultraviolet radiation, it is first converted to previtamin D3, which is automatically isomerized to vitamin D3 after 36 hours at body temperature.

(2) Liver: Subsultural conversion of vitamin D3 produced and absorbed by the intestines, combined with vitamin D binding protein (DBP) transported to the liver, vitamin D-25 hydroxylase catalysis in the hepatocellular particles catalyzed, into 25-(OH)D3. Vitamin D-25 hydroxylase is inhibited by feedback from product 25-(OH)D3. Synthetic 25-(OH)D3 is then transported in combination with DBP, the main form of vitamin D3 in plasma.

(3) Kidneys: 25-OH D3 produced by the liver is transported by blood to the kidneys and transformed into 1,25-(OH)2D3 under the action of the 1 alpha-hydroxygenase system (including jaundase, ferrothione protein, and cytochrome P450) in the telomeres of the epithelial cells of the renal epithelial tube. In addition, there are metabolites such as 24, 25-(OH) 2D3 and 1,24,25-(OH)2D3 in the kidneys. Its activity is weak.

(4) regulation: 1,25-(OH)2D3 synthesis is affected and regulated by a variety of factors. Mainly regulated by 1 alpha-hydroxylase, the main factors are PTH, blood and extracellular liquid phosphate concentration, 1,25-(OH) 2D3 and blood calcium.

PTH is the primary regulator of 1 alpha-hydroxyase. PTH promotes the synthesis of 1 alpha-hydroxyase and inhibits 24 alpha-hydroxyase, which increases the transformation of 25-(OH) D3 into 1,25-(OH)2D3 and into a decrease of 24,25-(OH)2D3. Low blood calcium stimulates the production of 1,25-(OH)2D3 by raising PTH. Low blood phosphorus stimulates the activity of 1 alpha-hydroxyase, and low blood phosphorus stimulates 1,25-(OH)2D3 synthesis without relying on PTH. In addition, vitamin D3 is not only immune to 1 alpha-hydroxylase, but also inhibits 1 alpha-hydroxyase.

2.1, 25-OH) 2D3 physiological effect

1,25-(OH) 2D3 action of the target organ is the small intestine, bone, but the effect on the kidneys is weak.

(1) on the small intestine: 1,25-(OH)2D3 can promote the absorption of calcium and phosphorus in the small intestine, which is its most important physiological work. 1,25-(OH)2D3 binds to specific cytosupal plasma subjects in small intestine mucous membrane cells and enters the nucleus, promoting DNA transcription to generate mRNA, which increases the synthesis of calcium binding proteins (Calcium binding, CaBp) and Ca2-Mg2-ATP enzymes.

so that into the absorption of Ca2 plus transshipment. At the same time, 1,25-(OH)2D3 can affect the synthesis of small intestine mucous membrane membrane phospholipids and the amount of fatty acids, increase the permeability of Ca2 plus, and benefit the absorption of Ca2 plus in the intestinal cavity. 1,25-OH)2D3 promotes Ca2 plus absorption along with the enhancement of phosphorus absorption, but the mechanism of phosphorus absorption is not yet clear.

(2) on the bone, 1,25-(OH)2D3 on the bone also has a double role in bone dissolution and bone forming. In-body experiments have shown that 1,25-(OH)2D3 stimulates bone-breaking cell activity and accelerates bone-breaking cell production, thus promoting bone-soluble action. In the body, it is in synergy with PTH to promote bone-breaking cell growth and enhance its bone-breaking effect.

other hand, because 1,25-(OH)2D3 increases the absorption of calcium and phosphorus in the small intestine, improves blood calcium, blood phosphorus, and promotes calcification. At the same time, 1,25-(OH)2D3 also stimulates bone cell secretion collagen, etc., to promote bone production. Therefore, when calcium and phosphorus supply is sufficient, 1,25-(OH)2D3 mainly promotes bone. When the blood calcium is reduced and the intestinal calcium is not absorbed enough, it mainly promotes the dissolved bone and makes the blood calcium rise.

(3) on the kidneys 1,25-(OH)2D3 can promote the renal tube to calcium, phosphorus re-absorption. However, this role is weak and secondary. Only in the bone growth and repair period, calcium, phosphorus supply shortage is more obvious.

1,25-(OH)2D3 total regulatory effect is to increase blood calcium, blood phosphorus.

(iii) calcitonin

1. Chemical essence

calcitonin is a single-stranded polypeptide hormone secreted by cells next to thyroid filth (also known as C cells), consisting of 32 amino acids with a molecular weight of 3500. N-end 1,7 amino acids are cysteine, connected by a sulfuric bond, forming a closed ring, C-end is proline. The order of amino acids inside the molecules changed greatly, and only 9 of the 32 amino acids were the same in different types of CT. But from the body structure, the structure of these CT is very similar, all of its hydrophobic and dredging.

the location of the amino acid residues in water is relatively fixed. Such as hydrophobic tyrosine, phenylalanine, lilacine in the molecule in a regular interval (4, 9, 12, 16, 19, 22 bits), charged acid amino acids are in 15 and 30 bits. Such as winterline, glutamate, glycine. So each CT has biological activity for a variety of mammals.

that CT bioactive activity is generally believed to depend on the integrity of the structure of 32 amino acids in molecules, there are some new insights and some new developments. For example, the synthetic synthesis of a single missing or missing piece of salmon CT from 19 22 amino acid residues, its calcium-reducing effect is twice that of natural salmon CT.

2.CT Synthesis and Secretion

The original translation product of CT mRNA as a template in human thyroid C cells was a protein with a molecular weight of about 15,000, which was modified to be first transformed into a product of a molecular weight of 12,000 and finally into a mature CT of 3500.

is the main factor affecting CT secretion. Increased blood calcium stimulates the secretion of CT. Lower blood calcium inhibits the secretion of CT, but the speed of CT synthesis is not affected, so the in-cell CT content increases. In patients with hypothyroidism, the CT content in their C cells also increased.

3.CT physiological function

CT action of the target organs are mainly bone and kidney, its role is the opposite of PTH, its role is to inhibit bone breaking, inhibit the re-absorption of calcium, phosphorus, reduce blood calcium and blood phosphorus.

has been found in the bone, kidney, intestinal mucous membrane, sperm and other cells have CT, CT and the subject in combination to activate adenosine cyclase, through cAMP to play a biological effect. Recently, it has been found that CT functional effects occur with the increase of ca2 plus in cells, and it has been suggested that Ca2 plus is the second messenger of CT acting on bone-breaking cells.

(1) CT on bone: CT directly inhibits the production of bone-breaking cells, but also accelerates the transformation of bone-breaking cells into bone-forming cells, thus enhancing bone-forming effects, inhibit bone salt dissolution, reduce blood calcium, blood phosphorus concentration.

(2) CT on the kidney effect: CT directly inhibits the renal tube to calcium, phosphorus ion re-absorption, so that urine phosphorus, urine calcium discharge increased, but also by inhibiting the kidney 1 alpha-hydroxylase and reduce the generation of 1,25-(OH) 2D3 and indirectly inhibit the absorption rate of calcium, phosphorus in the intestine, resulting in a decrease in plasma calcium, phosphorus levels.

(3) on the small intestine: indirectly inhibits calcium absorption by inhibiting 1,25-(OH)2D3 production, which is generally considered to have no direct effect.

can be seen, PTH, 1,25-(OH) 2D3, and CT can regulate calcium, phosphorus metabolism, the three coordinate with each other, mutual restriction, in order to maintain the dynamic balance of calcium and phosphorus in the blood. The metabolism of calcium and phosphorus is summarized in Table 12-2.

table 12-2 Three hormones regulate calcium and phosphorus metabolism