Histidine is an α - amino acid with chemical formula CsixHnineNthreeOtwoHistidine was first separated by German physicist Ebrecht Kossel in 1896.In the field of nutrition, histidine is considered as an essential amino acid for human beings, mainly for children.In adulthood, humans began to synthesize histidine by themselves.When a small amount of histidine is added to the diet of chronic uremic patients, the speed of amino acid binding into hemoglobin increases, and nephrogenic anemia decreases, so histidine is also an essential amino acid for uremic patients.Under the action of histidine decarboxylase, histidine decarboxylates to form histamine.Histamine has a strong vasodilator effect and is related to a variety of allergic reactions and inflammation.[2]In addition, histamine stimulates pepsin and gastric acid.
α - amino β - imidazolyl propionic acid belongs to basic amino acid or heterocyclic amino acid.The red color is produced by the Paouli reaction, that is, the reaction with diazobenzene sulfonic acid.D, D, L - and mixers (L means left in Latin, D means DEXTRO in Latin, right means right, and D and L refer to the chirality of amino acid molecular structure) exist in globin.It is also a carnosine component in muscle.L-histidine is colorless flake or needle shaped crystal, odorless, slightly bitter.Soften at 227 ℃ and decompose at 277 ℃.Soluble in water.Polarity - 39.4 ° (c=1.13 in water).It is made from dry flour, pig and cow blood powder, pig hair or hoof nail, or from glucose fermentation.Compared with other amino acids, histidine, in addition to some common chemical reactions, can form a brownish red compound, namely the Pauly reaction, due to its right side chain imidazolyl group and diazobenzenesulfonic acid.Since the dissociation constant of imidazolyl group is 6.0, that is, the concentration of dissociated protons is similar to that of water, histidine can be used as both proton donor and proton acceptor.[1]
purpose
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It is an important component of amino acid infusion and comprehensive amino acid preparation. It is used in medicine to treat gastric ulcer, anemia, allergy, etc.
On the other hand, the imidazolyl group gives and receives protons at a very fast speed, with a half-life of less than 10-10s, and the speed of giving and receiving protons is almost the same.Histidine residues are often active centers in active proteins.Histidine is a semi essential amino acid, which can be used as medicine or biochemical reagent.For human body, histidine can be synthesized by ordinary intermediate metabolites, so it has been considered as a nonessential amino acid. However, with the deepening of research, it has been found that the amount of histidine synthesis in young animals and infants cannot meet the growth needs of the body, even in adult animals, if it is not supplemented from food, it cannot meet the needs of the body,Therefore, it is also called semi essential amino acid.
Histidine is also one of the necessary raw materials for the synthesis of some pharmaceutical intermediates, such as the blue copper peptide ghk cu
It has been known that the main metabolic pathways in organisms are deamination through histidine deaminase, formation of histamine through decarboxylase and amino transfer reaction.Biosynthesis is the formation of imidazole glycerophosphate from the adenine part of ATP and phosphoribosyl filament phosphate to carry out the amino conversion reaction.
L-histidine is a semi essential amino acid, which is particularly important for the growth of infants and animals.It can be used as biochemical reagent and medicament, and also can be used to treat heart disease, anemia, rheumatoid arthritis, etc.[1]Histidine is found in bananas, grapes, meat, livestock, milk and dairy products.In addition, histidine also exists in green vegetables, but the content is less.
pharmacological action
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Imidazolyl energy of histidine and Fe2+Or other metal ions form coordination compounds to promote the absorption of iron, which can be used to prevent anemia.Histidine can reduce the acidity of gastric juice, ease the pain of gastrointestinal surgery, relieve vomiting and heartburn during pregnancy, inhibit the ulceration of digestive tract caused by autonomic nervous tension, and also have effects on allergic diseases, such as asthma.In addition, histidine can dilate blood vessels, reduce blood pressure, and is clinically used for the treatment of angina pectoris, cardiac insufficiency and other diseases.The content of histidine in the blood of patients with rheumatoid arthritis was significantly reduced. After the use of histidine, it was found that the grip strength, walking and erythrocyte sedimentation rate were improved.
Pharmacopoeia information
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This product is L-2-amino-3 - (1H-Imidazole-4) propionic acid, calculated as dry product, containing CsixHnineNthreeOtwoNot less than 99.0%.
character
This product is white or almost white crystal or crystalline powder, odorless.
This product is dissolved in water, very slightly soluble in ethanol, and insoluble in ether.
Specific curl
Take this product, weigh it precisely, add 6mol/L hydrochloric acid solution to dissolve it and dilute it quantitatively to make a solution containing about 0.11g per 1mL. Determine according to the law (general rule 0621), and the specific rotation is+12.0 ° to+12.8 °.
identify
1. Take an appropriate amount of this product and histidine control, add water to dissolve and dilute them respectively to prepare a solution containing about 0.4mg per 1mL as the test solution and control solution.According to the method under other amino acids, the position and color of the main spot of the test solution should be the same as that of the control solution.
2. The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 981 figure).
inspect
PH
Take 1.0g of this product, add 50mL of water to dissolve it, and then measure it according to the law (general rule 0631). The pH value should be 7.0~8.5.
Transmittance of solution
Take 0.60g of this product, add 20mL of water to dissolve it, and then measure the transmittance at the wavelength of 430nm according to the ultraviolet visible spectrophotometry (general rule 0401), which shall not be less than 98.0%.
chloride
Take 0.25g of this product and check it according to the law (general rule 0801). Compared with the control solution made of 5.0mL of standard sodium chloride solution, it should not be more concentrated (0.02%).
sulfate
Take 1.0g of this product and check it according to the law (general rule 0802). Compared with the control solution made of 2.0mL of standard potassium sulfate solution, it should not be more concentrated (0.02%).
ammonium salt
Take 0.10g of this product and check it according to the law (general rule 0808). Compared with the control solution made of 2.0mL of standard ammonium chloride solution, it should not be deeper (0.02%).
Other amino acids
Test according to thin layer chromatography (general rule 0502).
Test solution: Take a proper amount of this product, add water to dissolve and dilute it to make a solution containing about 10mg per 1mL.
Reference solution: precisely measure 1mL of the test solution, place it in a 200mL volumetric flask, dilute it with water to the scale, and shake it up.
System suitability solution: Take an appropriate amount of histidine control and proline control, place them in the same measuring flask, add water to dissolve and dilute them to make a solution with about 0.4 mg per 1mL.
Chromatographic conditions: silica gel G thin layer plate is used, and n-propanol concentrated ammonia solution (67:33) is used as developing agent.
Determination method: take 5 µ L of each of the above three solutions, dab them on the same thin-layer plate, develop them, dry them, spray ninhydrin acetone solution (1 → 50), heat them at 80 ℃ until spots appear, and inspect them immediately.
System suitability requirements: the reference solution should show a clear spot, and the system suitability solution should show two completely separated spots.
Limit: If the test solution shows impurity spots, its color shall not be deeper (0.5%) than the main spot of the control solution.
Loss on drying
Take this product and dry it at 105 ℃ for 3 hours. The weight loss shall not exceed 0.2% (general rule 0831).
Ignition residue
Not more than 0.1% (general rule 0841).
ferric salt
Take 1.0g of this product and check it according to the law (general rule 0807). Compared with the control solution made of 1.0mL of standard iron solution, it should not be deeper (0.001%).
heavy metal
Take 1.0g of this product and check it according to the law (General Rule 0821, Method 1). The content of heavy metals should not exceed 10% per million.
Arsenite
Take 2.0g of this product, add 23mL of water to dissolve it, add 5mL of hydrochloric acid, and check according to the law (the first method of general rule 0822), which should meet the requirements (0.0001%).
Bacterial endotoxin
Take this product and check it according to the law (general rule 1143). The endotoxin content in every 1g of histidine should be less than 6.0EU at most.(for injection)
Assay
Take about 0.15g of this product, precisely weigh it, add 2mL of anhydrous formic acid to dissolve it, add 50mL of glacial acetic acid, titrate it with perchloric acid titrant (0.1mol/L) according to the potentiometric titration method (General Rule 0701), and correct the titration result with a blank test.Every 1mL perchloric acid titrant (0.1mol/L) is equivalent to 15.52mg CsixHnineNthreeOtwo。
