TsISTEYN — - (a 3-merkaptoa lanin, or-a-amino-(3-merkaptopropiono-vaya acid; neutral aliphatic replaceable sulfur-containing amino acid, HS—СН2—CH(NH2) — — SOON, is a part of proteins and natural peptides. With at ljfgidr ilny groups (see) the remains of cysteine participate in formation of the catalytic center of many enzymes (see), napr, papain (see). Cysteine is an important link of the mechanism of inclusion of inorganic sulfur (see) in composition of organic matters. At oxidation of two molecules of cysteine between their sulphhydryl groups the disulfide bridge connecting these molecules in a molecule of a disulfide of C is formed. — cystine (see):
This reaction is reversible in this connection the system cysteine — cystine represents an important redox system of a cell (see Redoxreactions). Property to form disulfide bridges also connections have, to-rye it is possible to consider derivative C., napr, glutathione (see), oxytocin (see), etc. From C. as a result of oxidation of its SH group and the subsequent decarboxylation (see) taurine is formed (see). At many carnivores and at the person the reflecting layer behind a retina of an eye (see the Retina) contains crystals zinc - cis-teinovogo a complex. The inherited disorder of exchange of cysteine — cystine in a human body leads to development of a serious hereditary illness — a cystinosis (see), In medicine crystal C. and its derivatives apply as pharmaceuticals.
C. is present at cells of all auto-and heterotrophic organisms, in many proteins (see) its abundance it is very considerable (e.g., in hemoglobin of the person it makes 1%). Blood serum of the person contains on average 1,18 mg! 100 ml of cysteine (together with cystine).
In a human body and animal C. it is synthesized as a result of a number of metabolic transformations from the activated form of methionine (see) — S-adenozilmetio-nina through gomotsistein,
Nin forming as a result of condensation with serine (see) tsistatio-(see), to-ry is split on C. and a-oxobutyric to - that
(see the scheme).
Scheme of biosynthesis of cysteine.
The recovered glutathione can recover not enzymatically cystine in cysteine. At plants of C. it is formed of sulfides and serine, and at microorganisms — of the atsetilse-rin interacting with hydrogen sulfide (see).
Pier. the weight (weight) of L-cysteine is equal to 121,16. The isoelectric point (see) this amino acid is at pH 5,02. The dissociation constant of SOON-, NH2-and SH-group is equal 1,71, 8,33 and 10,3 respectively; L - cis-the theine emitted from biol. objects, has a crystal structure, specific rotation of the plane of the polarized light at 20 ° — [a]2^ — is equal +6,3 ° (concentration of cysteine of 8 g in 100 ml 1 N salt to - you). C. let's well dissolve in water, ammonia, acetic to - those, ethanol and it is insoluble on air, benzene, acetone. C. it is chemically unstable, easily is oxidized on air, especially in alkaline condition in the presence of metals, turning into hydrogen sulfide, ammonia and pyroracemic to - that.
For qualitative test of C. the studied test is processed phosphatotungstic to - that (Folin's reactant) or Sodium nitroprussidum in the alkalescent environment, in the presence in test of cysteine there is a red coloring, and at interaction with 1,2-naf-tokhinon-4-sodium sulphonate —
red-brown (Sallie vein reaction). For quantitative determination of C. the studied protein of an obr
batyvat surplus peroxyformic to - you, at the same time the remains of C. and cystine are oxidized to cysteic to - you: H03S - СН2 — CH(NH2) —
— SOON. After full hydrolysis of the studied protein cysteic to - that is defined hromatografichesk (see the Chromatography). Other quantitative method of determination of C. consists in recovery of C. excess of mercaptoethanol in 6M a gua-nidingidrokhlorida, at the same time forms the remains of C., to-rye in reaction with iodacetate quantitatively turn into the S-carboxymethyl-cysteine defined also hromatografichesk. For determination of content of C. in the studied protein establish the number of free SH-group by means of Ellman's reactant — 5,5 '-a dithiobis (2-nitroben-zoynoy to - you). The quantity formed by the thionitrobenzoic to - you, the defined spektrofotometricheska at pH 8,0 and the wavelength of 412 nanometers (see the Range about photometry), corresponds to the number of C. in the studied test.
At animals and the person Ts. it cannot be synthesized by direct inclusion of sulfide in composition of organic matters therefore it shall or arrive with food, or be synthesized from the methionine arriving with food. However transformation of methionine into C. in a human body has ogra-
nichenny character therefore children shall receive C surely. with food. Approximately average need of the adult for cysteine makes 4 — 6 g a day.
In a human body and animal C. can be exposed to a catabolism or join in various biosynthetic processes. At nek-ry bacteria splitting of C. leads to formation of hydrogen sulfide, pyroracemic to - you (pyruvate) and ammonia. At interamination of C. it is formed R-merkaptopiruvat, to-ry it is recovered to pyruvate and sulfide. Enzymatic reaction of r-substitution leads to transformation of cysteine in | 3-tsianalanin — the factor which is present at nek-ry plants (especially in bean, e.g. Lathyris adoratus) and the lathyrism causing in animals and the person (see). The development of defect in structure of collagen conducting to patol. to changes of connecting fabric at a lathyrism, can become the reason of deformation of a backbone, and in hard cases — a rupture of a wall of an aorta.
Cysteine as drug. In medicine as medicine use crystal cysteine, the combined drug Viceinum containing cysteine, and its nek-ry derivatives (Acetylcysteinum, Penicillaminum).
There are data that C. actively participates in a metabolism of lens (see) and that the biochemical changes happening in a crystalline lens at a cataract (see), especially at a senile cataract are connected with disturbance of exchange and content of this amino acid in a crystalline lens. Therefore for an arrest of development of a cataract and an enlightenment of a crystalline lens at initial stages senile, traumatic, complicated (at a myopia, uveites) and a beam cataract began to apply cysteine.
Cysteinum represents white crystal powder with a peculiar smell, easily water soluble; water solutions of cysteine are unstable since. C. in them easily is oxidized oxygen of air with formation of an insoluble residue — cystine. At sterilization of water solutions heating drug decays. C. apply in Ophthalmolum. to practice in the form of 2% of water solution, to-ry enter into tissues of an eye by means of an electrophoresis (see) or eye trays. Water solution of cysteine of the same concentration can be applied to instillations in a conjunctival sac. Treatment of traumatic cataracts of C. it is allowed in 2 — 3 months after their education.
A contraindication to use of C. increase in intraocular pressure, a back polar (bowl-shaped) cataract serves, the current a cut can become complicated as a result of Ts.
Form's use of release: powder in densely corked bottles of dark glass on 10 g. Solutions prepare ex tempore. Storage: in the dry, cool, protected from light place.
Since water solutions of cysteine are unstable and shall prepare just before use, for the eye drops containing C., prefer to use special drug Viceinum (viceinum). It is the combined drug containing cysteine of 0,2 g to - you glutaminic and glycine (glycine) on 0,1 g, 1% of solution of sodium salt adenosine triphosphoric to - you are 0,5 ml, Thiamini bromidum of 0,02 g, to - you nicotinic 0,03 g, potassium of iodide of 1,5 g, Calcii chloridum and magnesium of chloride on 0,3 g, isotonic solution of sodium of chloride to 100 ml. Viceinum represents a transparent colorless liquid with a light smell of cysteine.
Indications to use: the same forms of a cataract, as at treatment of C., at moderate decrease in visual acuity (not lower than 0,5). Appoint about 2 drops in a sore eye 3 — 4 times a day are long.
Form of release: on 10 ml in bottles of dark glass; storage: in the cool place protected from light. During the breaking of cystine of a drop become unsuitable to the use. At the correct storage of a drop there are transparent 8 — 10 days.
On action foreign drugs Vitaiodurolum (Vita-jodurol), Vitaphakolum and katakhry are close to Viceinum.
Acetyl cysteine [Acetylcys-teinum; synonym: Mucosolvinum (G), Broncholysinum (Ch), Acetein, Airbron, Bron-cholysin, Fluimucetin, Mucisol, Mu-cosolvin, etc.], N - acetyl - - cis-theine.
Acetyl derivative C., treats expectorants (see) direct actions, i.e. the mucolytic (sekretolitichesky) means liquefying a phlegm thanks to a depolymerization of the glikozaminoglikan which are its part (see Mucopolysaccharides); drug liquefies also pus.
Acetylcysteinum represents yellow-white crystal powder with a slight specific smell, well water soluble and alcohol; pH of 20% of water solution 7,0 — 7,5.
Acetylcysteinum is applied at acute and hron. bronchitis, infectious and allergic bronchial asthma, pneumonia, a bronchoectatic disease, a mucoviscidosis, etc., and also preventively appoint at operations on a respiratory organs and after an intratracheal anesthesia. At bronchial asthma recommend to appoint at the same time broncholitic means for the purpose of prevention of strengthening of a bronchospasm.
Acetylcysteinum apply in the form of inhalations on 2 — 5 ml 20% of solution
3 — 4 times a day (duration of inhalation of an aerosol of 15 — 30 min.), vnutritrakhealno enter on 1 ml 10% of solution each hour (in the form of slow instillation), solutions apply 5 — 10% to a bronchial lavage. At impossibility of inhalation introduction Acetylcysteinum is entered intramusculary, the adult — on 1 — 2 ml of 10% of solution 2 — 3 times a day, to children of chest age — 10 — 15 mg on 1 kg of the weight (weight) of a body
2 times a day, to children 1 years — on 0,5 — 1 ml of 10% of solution 2 times a day are more senior. Usually the course of treatment proceeds 1 — 2 week, at a tracheobronchitis —
3 — 4 days, at a mucoviscidosis —
7 — 10 days.
Acetylcysteinum is most often transferred well, nausea because of a specific smell of drug is sometimes possible. With care it is necessary to apply Acetylcysteinum at tendency of patients to a bronchospasm, pulmonary bleedings, at diseases of a liver, kidneys, dysfunction of adrenal glands.
Do not recommend to mix Acetylcysteinum with solutions of antibiotics and proteolytic enzymes because of a possible inactivation of drug. During the work it is necessary to avoid contact of drug with metals and rubber since in these cases formation of sulfides with an unpleasant characteristic smell is possible.
Form of release: 20% solution for inhalations in ampoules on 5 and 10 ml and 10% solution for injections in ampoules on
2 ml. Storage: in the place protected from light at a temperature of 0 — 5 °; joint venture.
B. Penitsillamin [Penicilla-minum; synonym: cuprenil (II), Arta-min, Beracilline, Guprenil, Depami-ne, Distamine, Mercaptyl, Metalcap-tase, Sulredox, Troloval, etc.], D-2-amino-Z-merkapto-Z-metilmaslya-naya to - that. Thanks to high ability to a complex formation (see. Complex connections) apply Penicillaminum as an antidote at acute and chronic poisonings with copper, mercury, lead, iron, calcium (see Poisonings, Antidotes). The formed non-toxic complexes are removed by kidneys. Penicillaminum is applied also at treatment of hepatocerebral dystrophy since drug strengthens removal of the copper which is contained much in tissues of such patients. According to the available data, Penicillaminum is in this respect more effective, than Unithiolum (see). Penicillaminum is effective also at treatment of a pseudorheumatism though the mechanism its anti-roar-matoidnogo of action is insufficiently clear. Believe that breaking off disulfide bridges in molecules of immunoglobulins (see), it destroys circulating patol. cell-bound immune complexes, the autoan-tigennost of immunoglobulin G reduces and slows down thus development of a rhematoid factor in an organism (see the Pseudorheumatism). Besides, it promotes accumulation of soluble and slows down formation of insoluble collagen. Penicillaminum is applied sometimes at a nephrolithiasis (to acceleration of removal of calcium), a scleroderma and a hemosiderosis.
Appoint Penicillaminum inside. Always use D-isomer since L-isomer and a racemate (see. Racemic connections) are more toxic. At hepatocerebral dystrophy apply up to 2 g of Penicillaminum in the first days of treatment, constantly controlling the general condition of the patient and a copper content in blood serum.
To children 6 years are more senior appoint 0,25 g of Penicillaminum once a day. In order to avoid side effect sometimes Penicillaminum is applied in smaller doses: since 0,15 g a day during 6 — 8 weeks and bringing later a dose to 0,9 g (but no more than 1,5 g) in days. High doses of Penicillaminum can cause hemolitic crisis as a result of the increased elimination of copper from a liver in blood. At improvement of a state the dose is reduced to 0,6 — 0,45 g a day. At the same time appoint a pyridoxine (see) on 60 — 100 mg a day. Treatment is carried out it is long, before permanent improvement of a condition of the patient. At a pseudorheumatism therapy is begun with 150 — 300 mg of drug a day. In each 2 — 4 weeks a dose increase on 150 mg to the general daily dose 600 — 750 mg (at most 900 mg). First signs of improvement of a state (reduction of a joint pain, morning constraint, etc.) appear usually in 2 — 3 months.
At use of Penicillaminum it is necessary to conduct weekly researches of urine and blood, to control the body temperature, concentration in blood of copper (at hepatocerebral dystrophy) or an ion of the metal which caused intoxication.
As by-effects at treatment by Penicillaminum leukopenias, thrombocytopenia, an agranulocytosis can develop, in urine there can be a protein and blood, note went. - kish. frustration, mialgiya, arthralgia, itch, urticaria.
As a contraindication to use of Penicillaminum serves the intolerance of penicillin or hypersensitivity to it.
Form of release: capsules and tablets on 0,15 and 0,25 g. Storage: at the room temperature in the dry place; joint venture. B.
See also Antidotes of OV, Amino acid, Complexons.
Bibliography: Mashkov M. D cue. Pharmaceuticals, p. 2, page 9 7, M.,
1 984; Metsler D. Biochemistry, the lane with English, t. 1 — 3, M., 1980; At and y t And. and d river. Fundamentals of biochemistry, the lane with English, t. 1 — 3, M., 1981.
A. M. Shaposhnikov (biochemical), N. G. Budko vsky (pharm.).