What Is the Connection between Phenylalanine and Tyrosine?

The chemical name of tyrosine (tyrosine; Tyr) is 2-amino-3-p-hydroxyphenylpropionic acid, which is an aromatic polar alpha-amino acid containing a phenolic hydroxyl group [1]. Tyrosine is an essential amino acid and ketogenic and glucogenic amino acid in the human body ^[1] .

Tyrosine was discovered by Li Biqi from casein in 1846. It is a white crystalline powder, crystallized from water into needles or flakes. The relative density is 1.456 (20 ° C), the isoelectric point is 5.66, it has the ability to absorb ultraviolet rays, has the maximum light absorption at a wavelength of 274nm, and can reduce phosphomolybdic acid-phosphotungstic acid reagent (Fulin reagent). Melting point: Decomposition at 290-295 ° C (slow heating), decomposition at 314-318 ° C (rapid heating), decomposition (slow heating) at 290-295 ° C, and decomposition (rapid heating) at 340 ° C. Soluble in water, ethanol, acid and alkali, insoluble in ether. The aqueous solution of dextrose reacts with tyrosinase and appears red. Levo-rotor can emit light by friction, and it can be converted into racemate by heating with barium hydroxide aqueous solution at 170 . The phenolic hydroxyl group in the tyrosine molecule is prone to chemical reaction. It is coupled with diazobenzenesulfonic acid to obtain an orange-red substance. The effect of dilute acetic acid and sodium nitrite is purple or red, yellow with warm nitric acid, and dark orange with titanium dioxide in sulfuric acid. Natural tyrosine is L-body, which can be obtained by hydrolyzing and refining protein ^[2] .

Chinese name: Tyrosine
Foreign name: tyrosine
CAS number: 60-18-4

Molecular formula: C9H11NO3
Molecular weight: 181.18900
PSA: 83.55000

Introduction to tyrosine compounds

Basic properties of tyrosine

Chinese name: Tyrosine

Chinese alias: (S) -2-amino-3-p-hydroxyl; (2S, 3R) -2-amino-3-p-hydroxyphenylpropionic acid; L-(-)-tyrosine; L--p Hydroxyphenyl--alanine; L--p-hydroxyphenyl--aminopropionic acid ^[3] ;

English name: tyrosine

English alias: msd803; Rovacor; LOVASTIN; Paschol; LOVALIP; Sivlor; MEVACOR; mevlor; L-Tyrosine; MEVINOLIN ^[3]

CAS number: 60-18-4 ^[3]

Molecular formula: C ₉ H ₁₁ NO _{3 ^[3]}

Molecular weight: 181.18900 ^[3]

Exact mass: 181.007400

PSA: 83.55000

LogP: 1.04690

Tyrosine physicochemical properties

Appearance and properties: white to off-white powder ^[3]

Density: 1.34 ^[3]

Melting point:> 300 ° C (dec.) (Lit.) ^[3]

Boiling point: 385.2ºC at 760 mmHg ^[3]

Flash point: 176 ° C ^[3]

Refractive index: -12 ° (C = 5, 1mol / L HCl) ^[3]

Water solubility: 0.45 g / L (25 ºC) ^[3]

Stability: stable, incompatible with strong oxidants and strong reducing agents ^[3]

Storage conditions: normal temperature and pressure ^[3]

Tyrosine Safety Information

Symbol: GHS07 ^[3]

Signal Word: Warning

Hazard statement: H315; H319; H335 ^[3]

Cautionary statement: P261; P305 + P351 + P338 ^[3]

Customs code: 29225000 ^[3]

WGK Germany: 3

Danger category code: R36 / 37/38 ^[3]

Safety instructions: S26-S36 ^[3]

RTECS number: YP2275600 ^[3]

Dangerous goods sign: Xi ^[3]

Tyrosine production method

1. Separated from acid hydrolysates of casein, silk and other proteins, the precipitate is separated, dissolved in dilute ammonia, neutralized with acetic acid to pH = 5, and obtained by recrystallization. The second crude crystalline pure solution of cystine was extracted from pig hair hydrolysate, and stored at 20 ° C or lower for two days to precipitate tyrosine and filtered to obtain crude tyrosine. L-tyrosine can also be obtained after purification. . The yield on pig hair was 1%.

2. Casein is used as raw material, refluxed in hydrochloric acid for several hours, filtered, concentrated, alkali neutralized, activated carbon treated, and crystallized to obtain the product.

3. After the acid hydrolysate of casein, silk, and other proteins are neutralized and separated by precipitation, it is dissolved in dilute aqueous ammonia and recrystallized when neutralized to pH 5 with acetic acid.

4. The preparation of L-tyrosine mainly adopts proteolytic extraction method. Pig blood powder, horn hoof, silk and other raw materials can be used, after acid hydrolysis, and then separated and purified.

Pig blood meal [HCl (hydrolysis)] [110 , 24h] Hydrolysis solution [Acid] [Evaporation and concentration] Acid removal solution [Activated carbon] Decolorization solution [Decolorization, cooling crystallization] L-tyrosine crude [Activated carbon] (Refined)] [90 ° C, 30min] filtrate [crystallization] L-tyrosine.

Hydrolysis and acid removal Put the pig blood meal, water, and industrial hydrochloric acid into the hydrolysis tank at a weight ratio of 1: 1.3: 1, heat them to 112-114 ° C, stir and reflux for 24 hours, and stop. Cool and filter to remove. The filtrate is the hydrolysis solution. . The hydrolysate was evaporated and concentrated to a syrupy state, and then water was added to dissolve and evaporate the concentrate. This was repeated three times to drive the acid. Decolorize and crystallize the concentrated solution, add distilled water to dilute to full solution, then add immersion ammonia to adjust the solution pH to 3.5, add 1% activated carbon, stir and boil for 10min, stir and hold in a 90 water bath for 30min, filter while hot, and wash the activated carbon layer with distilled water 3 The filtrate and washings were combined. According to this method, decolorization with activated carbon was continued until the solution became pale yellow. The filtrate was left at below 10 ° C for 24 hours, and crystals were precipitated. The crude L-tyrosine was obtained by filtration. Recrystallization Refining Add crude tyrosine to distilled water at 1:20, let it dissolve completely, then add 1% activated carbon, stir at 90 ° C for 30 minutes, filter while hot, and cool the filtrate to refine and precipitate crystals. The crystals were collected by filtration, washed twice with absolute ethanol, and dried at 60 ° C to obtain a finished product of L-tyrosine ^[2] .

Tyrosine use

APIs, food additives

Specific optical rotation: l-body: -10.6 ° (c = 4.1mol / LHCl, 25 ° C); d-body: + 10.3 ° C (c = 4.1mol / LHCl). Co-heating with sugars can produce a reaction between aminocarbonyl groups, resulting in a special flavor.

Tyrosine is a catalytic substrate for tyrosinase monophenolase function and is the main raw material for the formation of melanin and melanin. In the research and development of whitening cosmetics, it is possible to effectively inhibit the production of melanin by studying the synthesis of tyrosinase structural analogs that compete with tyrosine.

Patients with vitiligo eat foods containing tyrosine to promote the formation of melanin and reduce the symptoms of vitiligo.

The raw materials of amino acid infusion and amino acid compound preparation are used as nutritional supplements. Treatment of polio, nuclear encephalitis and hyperthyroidism. It is also used as a raw material for the production of diiodotyrosine, dibromotyrosine and L-dopa ^[4] .

other:

Amino acid drugs The raw materials of amino acid infusion and amino acid compound preparation are used as nutritional supplements. For the treatment of polio and tuberculous encephalitis / hyperthyroidism.

2. Nutritional supplements. It is used in medicine to treat myelitis, tuberculous encephalitis, hyperthyroidism and other symptoms. It is also used to make L-dopa diiodotyrosine. After co-heating with carbohydrates, an aminocarbonyl reaction can generate special flavor substances.

3. Used in biochemical research, used as amino acid nutrition medicine in medicine, to treat diseases such as polio, encephalitis, and hyperthyroidism.

4. Biochemical reagents and APIs. Non-essential amino acids.

5. Available for tissue culture (L-tyrosine · 2Na · H2O), biochemical reagents, and treatment of hyperthyroidism. It can also be used as a nutrient for the elderly, children's food and plant foliage ^[2] .

Tyrosine Pharmacopoeia Standard

Tyrosine source (name), content (potency)

This product is L-2-amino-3- (4-hydroxyphenyl) propionic acid. Calculated on dry basis, the content of C ₉ H ₁₁ NO ₃ should not be less than 99.0% ^[5] .

Tyrosine traits

This product is white crystal or crystalline powder; odorless and tasteless.

This product is very slightly soluble in water, insoluble in anhydrous ethanol, methanol or acetone; it is soluble in dilute hydrochloric acid or dilute nitric acid ^[5] .

Tyrosine specific rotation

Take this product, weigh it accurately, add 1mol / L hydrochloric acid solution to dissolve and quantitatively dilute it to make a solution containing about 50mg per 1ml, and measure it according to the law (Appendix VIE of the second edition of the Pharmacopoeia, 2010 edition). The specific rotation is -11.3 ° to- 12.1 ° ^[5] .

Tyrosine identification

(1) Take appropriate amounts of this product and tyrosine reference substance, respectively add dilute ammonia solution (concentrated ammonia solution 14 100) to dissolve and dilute to make a solution containing about 0.4mg per 1ml, as the test solution and control Product solution. According to the chromatographic conditions test under other amino acids, the position and color of the main spots displayed by the test solution should be the same as the main spots of the reference solution.

(2) The infrared light absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Drugs" 1072).

Tyrosine test

1.Acidity

Take 0.02g of this product, add 100ml of water to make a saturated aqueous solution, and determine it according to law (Appendix VI H of the second edition of the Pharmacopoeia 2010), the pH value should be 5.0 ~ 6.5.

2.Transmittance of solution

Take 1.0g of this product, add 20ml of 1mol / L hydrochloric acid solution to dissolve, and measure the light transmittance at 430nm according to UV-Vis spectrophotometry (2010 edition Pharmacopoeia Part II Appendix IV), and the light transmittance shall not be lower than 95.0%.

3.Chloride

Take 0.25g of this product and check it according to law (Appendix A of Part Two of the 2010 Pharmacopoeia). It must not be more concentrated (0.02%) than the control solution made from 5.0ml of standard sodium chloride solution.

4.Sulfate

Take 1.0g of this product, add 40ml of water to warm to dissolve, let cool, check according to law (Appendix B of the second edition of the Pharmacopoeia 2010), compared with the standard potassium sulfate solution 2.0ml control solution made in the same method, it must not be more concentrated (0.02% ).

5.Ammonium salt

Take 0.10g of this product and check it according to law (Appendix K of the second edition of the Pharmacopoeia 2010), compared with the control solution made of 2.0ml of standard ammonium chloride solution.

6.Other amino acids

Take an appropriate amount of this product, add dilute ammonia solution (concentrated ammonia solution 14 100) to dissolve and dilute to make a solution containing about 10mg per 1ml as the test solution; take 1ml precisely, place it in a 250ml measuring bottle, use the above Dilute the dilute ammonia solution to the mark, shake well, and use it as the control solution. Take another appropriate amount of the tyrosine reference substance and the phenylalanine reference substance, put them in the same volume bottle, add the above dilute ammonia solution to dissolve and dilute to make 1ml Each solution contained about 0.4 mg as a system suitability test solution. According to the thin-layer chromatography (2010 Appendix B Pharmacopoeia Part II) test, draw 2 l of each of the above three solutions, point them on the same silica gel G thin-layer plate, and use n-propanol concentrated ammonia solution (7: 3) as the developing agent. , Unfolded, air-dried, sprayed with ninhydrin acetone solution (1 50), heated at 80 ° C until spots appeared, and inspected immediately. The control solution should show a clear spot, and the system suitability test solution should show two completely separated spots. If the test solution has obvious spots of impurities, its color must not be darker than the main spots of the control solution (0.4%) ^[5] .

7.Dry weight loss

Take this product and dry it at 105 ° C for 3 hours, and the weight loss shall not exceed 0.2% (Appendix L of Pharmacopoeia Part II of 2010 Edition) ^[5] .

8, burning residue

Take 2.0g of this product and check it according to law (Appendix N of Part II of the Pharmacopoeia of 2010 Edition). The residual residue shall not exceed 0.1% ^[5] .

9.Iron salt

Take 1.0g of this product, after burning and ashing, add 2ml of hydrochloric acid to the residue, evaporate it in a water bath, add 4ml of dilute hydrochloric acid, and dissolve it with slight heat, add 30ml of water and 50mg of ammonium persulfate, and check according to law (Appendix G), compared with the standard iron 1.0ml standard iron solution, it must not be deeper (0.001%).

10.Heavy metals

Take the residue left under the item of burning residue and check it according to law (Appendix H, the second method of the Pharmacopoeia of the 2010 edition, the second method). The content of heavy metals must not exceed 10 parts per million.

11.Arsenic salts

Take 2.0g of this product, add 5ml of hydrochloric acid and 23ml of water to dissolve it, and check it according to law (Appendix J of the second edition of the Pharmacopoeia of 2010 Edition J first method), which should meet the requirements (0.0001%).

12.Bacterial endotoxin

Take 1g of this product, add 100ml of endotoxin test water to make a saturated solution, and take the supernatant to check according to law (Appendix E of the second edition of the Pharmacopoeia of 2010 Edition). The amount of endotoxin in 1ml of tyrosine saturated solution should be less than 0.25EU ( (For injection) ^[5] .

Determination of tyrosine

Take about 0.15g of this product, accurately weigh, add 6ml of anhydrous formic acid to dissolve, add 50ml of glacial acetic acid, according to the potentiometric titration method (Appendix A of the second edition of the Pharmacopoeia, 2010 edition), and use perchloric acid titration solution (0.1mol / L) Titrate and correct the results of the titration with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 18.12mg of C ₉ H ₁₁ NO _{3 ^[5]} .

Tyrosine involves food

Cheese, chocolate and citrous fruit, pickled sardines, tomatoes, milk, lactic acid drinks, cheese, animal liver, beef, yogurt, condensed milk, sausage, ham, fermented food, broad beans, lentils, pineapple , Banana, fig, tea (various beverages and foods containing caffeine), white wine, fruit wine, beer, vinegar, miso, bean curd, stinky tofu, pine eggs, pickled products (such as sauerkraut, kimchi, etc.), Fish, blue ginseng, horse mackerel, tuna, band fish, sea bass, catfish, yellow croaker, mackerel, carp, oysters, crab, abalone and more.

Tyrosine intake

The typical dose of tyrosine is about 1 to 2 grams per day. As an antidepressant, take 500 to 1000 mg two to three times a day.

Because tyrosine has a stimulating and antidepressant effect, taking 1000 to 1500 mg of tryptophan in the morning and before lunch (tryptophan calms people), then at night it will have a good therapeutic effect on reducing depression. Researchers have found that for some people, the use of tryptophan and tyrosine together is better than tyrosine or tryptophan alone in reducing depression.

Tyrosine metabolism in vivo

Tyrosine is an amino acid that constitutes a protein. It has an ionized aromatic ring side chain and is hydrophilic. Tyrosine is produced by the hydroxylation of phenylalanine in humans and animals. Essential amino acids.

The catabolism of tyrosine is first converted into p-hydroxyphenylpyruvate under the catalysis of tyrosine aminotransferase in the liver. This enzyme requires pyridoxal phosphate as a coenzyme. P-hydroxyphenylpyruvate causes the oxidative decarboxylation and transfer of side-chain pyruvate and the hydroxylation of the ortho position of the phenyl ring through the action of p-hydroxyphenylpyruvate hydroxylase to form urinic acid (dihydroxyphenylacetic acid). This enzyme is a copper-containing metal protein that requires ascorbic acid to act as a coenzyme and consume molecular oxygen. Uric acid is catalyzed by uric acid dioxygenase (uric acid oxidase), which splits the benzene ring to produce maleic acetoacetate. This enzyme is a metal protein containing iron, and the reaction requires a molecule of oxygen to participate . Maleic acetoacetate is converted to fumarate acetoacetate by the action of the corresponding isomerase, which requires glutathione as a coenzyme. Finally, it is hydrolyzed to fumaric acid and acetoacetic acid by the corresponding hydrolase, so tyrosine is both a raw sugar and a ketogenic amino acid.