METHIONINE — alpha amino - gamma methylthiobutyric acid, CH 3 SCH 2 CH 2 • CH(NH 2 ) COOH, the sulfur-containing monoamino monocarboxylic acid, irreplaceable for the person and animals, which is a part of many proteins. Thanks to existence of labile methyl group M. it is necessary for implementation of reactions of transmethylation (see. Transmethylation ), leading to biosynthesis creatine (see), sincaline (see), adrenaline (see) and other biologically active agents, and also for neutralization of various toxic metabolites. M.'s lack is followed by serious violations of a metabolism, first of all exchange lipids (see), is also the reason of severe damages of a liver, in particular its fatty infiltration. Hereditarily the caused disturbances of exchange of M. are the reason of a serious illness. In M.'s medicine it is applied as medicine. Mechenny 75 Se M. is used for diagnosis of diseases of gepatobiliarny system and other diseases.
M.'s maintenance is much higher in proteins of animal origin, than in phytalbumins. Especially there is a lot of it in ovalbumin (5%) and casein of milk (3,5%).
Cottage cheese, cheeses, lactic products, eggs, meat of various animals, bean are the main source of arrival of M. for the person.
The blood plasma of the person contains 0,4 — 0,45 mg of % of M. The adult needs to receive M. with food at the rate of 31 mg on 1 kg of weight a day, to children — 85 mg on 1 kg of weight.
For the first time M. was found by Müller (J. N of Mueller) in casein in 1922 it is also synthesized in 1928. G. Barger and Koyn (F. Rubles of Coyne), to-rye also called new amino acid methionine.
The m represents white crystal powder, its pier. weight (weight) 149,21; t ° pl 283 ° (with decomposition), solubility of 3,35 g in 100 g of water at 25 °, the Isoelectric point is at pH 5,74.
Natural proteins contain L-methionine though in the nature also D-isomer meets. D-methionine is utilized by a human body completely though its intracellular transport in comparison with L - izome-rum is complicated.
Quantitative and qualitative test of M. is carried usually out by methods chromatography (see). There is also colorimetric method of quantitative definition of M. on staining reaction with Sodium nitroprussidum in strongly alkaline condition (see. Nitroprussiate reaction ).
M.'s biosynthesis from asparaginic to - you are established only in plants and at nek-ry microorganisms. Cysteine is a source of sulfur for M. A direct predecessor M. is gomotsistein, methylation to-rogo with the participation of coenzymatical forms folic acid (see) and B12 vitamin (see. Cyanocobalamine ) it is carried out in an organism of mammals. However gomotsistein does not contain in proteins of food of the person and mammals therefore M.'s arrival with food is for them absolutely necessary.
The m is soaked up in a small bowel and comes to a liver where is exposed to the main transformations. Its oxidizing deamination (see) in a liver under the influence of an oxidase of L-amino acids (KF 18.104.22.168) or that is more probable, it transamination (see) with alpha and keto-glutaric to - that leads to education alpha keto - gamma methylthiooil to - you.
The main pathway of Methionine passes through formation of cysteine in three stages:
Earlier believed that tsistationin (see) it is split under the influence of specific enzyme of a tsistationaza (homoserine-dehydratase; KF 22.214.171.124) to cysteine and homoserine, however such way, probably, is not characteristic of M.'s transformation in tissues of animals.
Education cysteine (see) from M. has important biol, value as the needs of an organism for cysteine can be realized almost completely at the expense of M.
M.'s transformation in gomotsistein is carried out through a mode of formation of an active form M. — S-hell-nozilmetionina, about the Crimea M.'s participation in reactions of transmethylation is connected. In experiences with M., marked on CH carbon 3 - groups, it is shown what in M.'s organism is a universal donor of CH 3 - groups. This main and, perhaps, unique biol, function M. is implemented through S-adenozilmetionin. Synthesis of S-adenozilmetionina is carried out in the enzymatic way with the participation of ATP:
Communication of sulfur atom M. with the rest of adenosine and emergence of positive charge lead to a labilization of CH 3 - groups, edges are easily transferred to the corresponding acceptors, napr, to glycocyamine in synthesis of creatine, to noradrenaline at formation of adrenaline, etc. S-Adenozilmetionin participates also in reactions of methylation ribonucleic to - t, and carbon his skeleton later decarboxylations (see) it is used at biosynthesis of polyamines, in particular spermine and spermidine. Along with coenzymatical forms folic to - you, vitamin B 12 and M.'s betaines forms a complex system of reactions of transmethylation in an organism. The fact that at insufficient receipt the fatty infiltration of a liver caused by insufficient synthesis develops in M.'s organism is explained by it, e.g. sincaline (see), CH 3 - groups to-rogo come from M. Inclusion in a diet of products, rich M. (e.g., cottage cheese), normalizes biosynthesis of sincaline and lipid metabolism in a liver.
M.'s desulphonation with eliminating of methyl mercaptan (CH 3 SH) has no big specific weight in M.'s exchange in tissues of animals and it is normal of the person, however at severe damages of a liver at the person methyl mercaptan appears in urine. Also characteristic off-flavor from a mouth of patients at nek-ry diseases of a liver is explained by its education.
M.'s rest in molecules of proteins, apparently, does not play an essential functional role; contents it in fermental proteins is, as a rule, small, and there are no direct data on participation of the remains of M. as functional groups during the formation of active centers of enzymes or in regulation of enzymatic activity. However M. holds key position at the initial stages of biosynthesis of protein in ribosomes, forming specific complexes about TRNK (formylmethionine-TRNK) and being an initiator of synthesis of a polypeptide chain. It is established for E. coli and for mitochondrions of zooblasts.
Disturbances of exchange
Disturbances of exchange of M. in a human body are connected generally with hereditary enzymopathies (see), the characterized total absence or insufficiency of the enzymes participating in its transformations.
The hereditary disease is known homocystinuria (see), M. caused by disturbance of exchange and connected with lack of L - serines-dehydratases in a liver. At such patients owing to blocking of synthesis of a tsistationin collects in fabrics gomotsistein, to-ry, being oxidized to homocystine, it is removed with urine in number from 50 to 200 mg and more in days. At this disease M.'s maintenance in blood can reach 29 mg of % (norm of 0,45 mg of %).
Other disease connected with disturbance of exchange of M. — tsistationinuriya (see) — it is characterized by the metabolic block on the way of splitting of a tsistationin, to-ry collects in tissue of a brain and it is allocated with urine in number from 0,5 to 1 and in days. It is revealed what tsistationin appears in urine at neuroblastomas, and also is present at fabrics of these tumors; S. Ya. Kaplansky pointed to a possibility of existence in fabrics of a neuroblastoma of specific inhibitor of the enzyme catalyzing splitting of a tsistationin.
For a wedge, the purposes M., marked 75Se is used. It has relative value for diagnosis of diseases of a pancreas and epithelial bodies and soft tissues because of absence to them specific tropism. Methionine-75Se is of great value at the research in vivo of gepatobiliarny system. With its help early and effective diagnosis patol, changes in a parenchyma of a liver is possible: dystrophies, necroses, cirrhoses, tumors; definition of an intra hepatic cholestasia, including at anicteric forms; differential diagnosis of jaundices.
Researches with methionine - 75 Se are carried out in tracer diagnostic laboratory. Usually methionine-75Se 250 — 300 mkkyur is entered by activity intravenously, and in 20 — 30 min. (pancreas) and 24 — 72 hours (tumors of epithelial bodies, soft tissues) the research on the scanning installation or the gamma camera is conducted. For a research of gepatobiliarny system methionine-75Se is entered orally on an empty stomach in a dose by 100 — 150 mkkyur. Further the research is conducted as in the functional plan (radiometry of all body with local shielding of a liver in 2 hours, on the 1st and then for the 7th days), and in functional and morphological (scanning of a liver in the same terms). This way is atraumatic, considerably reduces the size of beam load of the patient and medical staff and simplifies the procedure of a research.
Methionine as drug
Metionin as drug (Methioninum; synonym: Acimetion, Ametionol, Athinon, Meonine, Metione, Thiomedon). The m represents white crystal, low solubility powder in water, with the smell characteristic of mercaptoconnections (a smell of hydrogen sulfide), slightly sweetish on taste. Products of formylation or M.'s acetylation — N-formil-and N-acetyl methionine — well rastvorima in water.
The m possesses the action expressed lipotropic caused by its ability to transfer mobile CH 3 - group on phosphatidylethanolamine at formation of sincaline in an organism. As medical drug M. is used first of all for treatment and the prevention of diseases and toxic damages of a liver: cirrhosis, damages of a liver arsenous drugs, chloroform, benzene, perchloromethane and other substances, toxic concerning a liver, at a diabetes mellitus, hron, alcoholism. The effect of drugs M. is most expressed when there is a fatty infiltration of a liver. The m is applied also to treatment of the dystrophy resulting from proteinaceous insufficiency after dysentery and other infectious diseases and in these cases M.'s use together with lipocainum is shown.
M.'s treatment atherosclerosis gives unstable and not always the expressed effect. Only at a part of patients, apparently with the insufficient content of phospholipids in a liver, M.'s reception can lead to decrease in concentration of cholesterol and strengthening of phospholipids in blood.
M appoint inside 3 — 4 times a day. The single dose for adult 0,5 — 1,5 g for children till 1 year — 0,1 g, up to 2 years — 0,2 g, from 3 to 4 years — 0,25 g, from 5 to years — 0,3 g, of 7 years is also more senior — on 0,5 g. Accept M. in 0,5 — 1 hour prior to food. Course of treatment of 10 — 30 days.
Forms of release: powder, tablets on 0,5 g and tablets, coated, on 0,25 g.
Storage: in well corked banks from dark glass in the place protected from light. Abroad M. is made also for intravenous injections (e.g., in the form of water soluble formiate M.). See also Lipotropic substances .
Bibliography: Braunstein A. E. On the ways to knowledge of reactions and enzymes of transfer of amino groups, Prepint, M., 1974; Lenindzher A. Biochemistry, the lane with English, page 24, etc., M., 1976; Mashkovsky M. D. Pharmaceuticals, p. 2, page 54, M., 1977; P and l and N to and sh and D. G. Use of methionine - Se75 for a research of exchange processes in a liver, Medical radio-gramophones., t. 17, No. 12, page 42, 1972; it, Radiometry of all body by means of me-thionine-Se75 for definition of an intra hepatic cholestasia, in the same place, t. 23, No. 11, page 32,1978; Purpose E. And. ifadeevn. P. Stsintigrafiya of tumors of soft tissues by means of 758e-methionine, in the same place, t. 21, No. 12, page 56, 1976; I am N of of L. and M about at J. Metabolism of compounds of sulfur, the lane with English. M, 1961.
T. T. Berezov, H. N. Chernov; D. G. Palinkasha (I am glad.), A. N. Klimov (pharm).