DEAMINATION — one of the main stages of exchange of nitrogenous compounds; represents process of eliminating of an amino group (NH 2 - groups) from organic compounds — amino acids, amines, aminopurines, aminopyrimidines, their nucleosides and nucleotides etc., NH which is followed by substitution 2 - any other group. In a metabolism of the person and animal D. plays a large role. In animal and vegetable organisms and at D.'s microorganisms results from effect of specific enzymes. The ammonia which is formed at D. turns further into end products of a nitrogen metabolism (urea, uric to - that, etc.) or is used for synthesis of the new amino acids and other nitrogenous compounds necessary for life activity of an organism (see. Nitrogen metabolism ). A part of ammonia is used for neutralization formed in an organism to - t and is removed with urine in the form of salts of ammonium (see. Acid-base equilibrium ).
In Nibiolum. systems D. it is carried out by action of chemical agents, such as, e.g., nitrogenous to - that or other nitrozilny connections. Of amino acids by their oxidation with formation of CO 2 and the corresponding aldehydes occurs under the influence of O 2 or H 2 O 2 in the presence of salts of the heavy metals playing a role of catalysts. Similar products are formed as a result of D. of amino acids at their interaction with quinones, mesoxalyl urea, isatin, ninhydrin (see). At interaction nitrogenous to - you with NH 2 - the group of amino acids and primary (aliphatic) amines releases molecular nitrogen:
There are several types of biochemical processes of D.
Oxidizing deamination of amino acids
One of the main types of D. at the person, mammal and other classes of animals oxidizing D. is:
Oxidizing D. can be carried out in two ways: direct and indirect (transdeamination). In an organism of hematothermal animals direct oxidizing D. of amino acids was for the first time revealed and studied by Neybauer (O. Neubauer) and F. Knoop in 1909 — 1911. It was later is reproduced in experiences with the isolated bodies, fabric cuts and cell-free preparations. In establishment of an oxidizing way of D. in tissues of animals the big role was played by G. Krebs's researches. It showed existence in a liver and kidneys of the fermental system catalyzing D. of amino acids. Action of this system was shown in aerobic conditions with oxygen consumption and formation of ammonia and ketonic acids on the overall equation 1. Of natural (L-) and not natural (D-) amino acids proceeded with various speed and under the influence of different enzymes which were called L-and D-dezaminazami (oxidases). For oxidizing D.'s enzymes of amino acids the International commission on enzymes offered the following names: an oxidase of L - Amino-acids (KF 188.8.131.52) and an oxidase of D-amino acids (KF 184.108.40.206). The oxidase of D-amino acids is found in kidneys and a liver of animals, and also in bacteria and pleseny. For the first time enzyme was emitted from kidneys of a pig; later its crystal drugs from different sources are received. These enzymes, as a rule, contain in quality of a coenzyme of FAD (see. Yellow enzymes ). Fiziol, a role of an oxidase of D-amino acids is up to the end not found out; consider that it consists in D. of the D-amino acids which are formed in intestines of L - Amino-acids of proteins of food under the influence of bacterial enzymes — racemases.
In 1944 D. Green and sotr. found in a liver of a number of animals enzyme the glitsinoksidaza which is selectively catalyzing. glycine (see) with education glyoxylic acid (see) and ammonia. This oxidase represents the yellow enzyme containing Riboflavinum-phosphate (FMN). The same year Green and sotr. allocated an oxidase of L-amino acids from kidneys of a rat. Unlike an oxidase of D-amino acids, it was in fiziol, conditions low-active and less widespread in the nature. The oxidase of L-amino acids (renal) oxidized usual monocarboxylic L - alpha amino acids (except glycine, threonine and serine) and is more active — corresponding to L - alpha oxyacids; diamino-and dicarbonic amino acids were not deaminized by this enzyme. A coenzyme of the oxidase of L-amino acids allocated from kidneys is FMN. Active oxidases of L-amino acids are received in the cleared and crystal view from poisons and tissues of snakes and from microorganisms. The oxidase of L-amino acids from poison of snakes contains in quality of a coenzyme two molecules FAD on one molecule of enzyme. In experiences with the purified drugs of oxidases D-and L-amino acids reaction proceeds on the equation:
As in vivo, and in experiences with the crude drugs of oxidases of L D-amino acids containing usually as impurity enzyme a catalase (KF 220.127.116.11) splitting hydrogen peroxide, oxidizing D.'s process of amino acids proceeds according to the overall equation 1. The mechanism of process can be schematically presented by the following reactions:
In the first, enzymatic, a phase of reaction amino acid gives two hydrogen atoms to an acceptor (FAD or FMN) and turns into alpha imino-acid. Hydrogen is transmitted further through system respiratory enzymes (see) to a final acceptor — oxygen, forming H 2 O (see. biological oxidation ). In the second, spontaneous, a phase of reaction unstable imino-acid is hydrolyzed with formation of ketonic acid and ammonia. The special specific flavinsoderzhashchy oxidases which are actively deaminizing aromatic L - ami-nokisloty, L-diamino acids and glycine, are found in tissues of a liver and kidneys of birds. In 1937 X. Euler-Helygin and sotr. for the first time emitted enzyme the glutamatdegidrogenaza which is specifically deaminizing L-glutaminic to - that to alpha and keto-glutaric to - you and ammonia. This enzyme is found at the person, animals, plants and microorganisms. It is found almost in all tissues of mammals, is most active in tissues of a liver, kidneys and hearts. Its action is reversible: in an organism at fiziol, conditions in the presence of alpha and keto-glutaric to - you and ammonia reaction is directed preferential towards synthesis glutamic acid (see). Enzyme is received from different sources in a crystal look. NAD or NADF takes part in its action (see. Coenzymes ).
Are also deaminized by an oxidizing way amines (see), formed in an organism at decarboxylation (see) amino acids. Many amines are toxic therefore their D. has big fiziol, value for an organism. Of amines proceeds with the participation of the corresponding aminoxidases on the equation:
The aldehydes which are formed in this reaction turn with the participation of oxidizing enzymes in corresponding to - you. Two main types of aminoxidases are known: monoamine oxidase (MAO; KF 18.104.22.168), acting on primary, secondary and basic nitriles (e.g., isoamylamine, tyramine, adrenaline, 5-oksitriptamin, etc.) and the diaminoxidases (KF 22.214.171.124) operating on a histamine, putrestsin, pentamethylenediamine, etc. These enzymes are found in a liver, kidneys, a mucous membrane of intestines, a blood plasma and other tissues of animals and the person, and also at plants and at many bacteria (see. Aminoxidases , Diaminoksidaza , Monoamine oxidase ). Some aminoxidases are received in the cleared look; one of them treat yellow enzymes, and others (a histaminase, a spermine oxydase from a blood plasma) — cupriferous proteids in which catalytic action probably pyridoxal phosphate or a cofactor, similar to it, participates.
Indirect oxidizing D. (trans-deamination) and synthesis of amino acids were for the first time theoretically predicted by the Soviet
biochemist A. E. Braunstein in 1937 — 1939; afterwards these representations were confirmed experimentally by A. E. Braunstein and it sotr., and then and researches of other authors. The mechanism a trance of deamination consists of two consecutive enzymatic reactions. In the first occurs interamination (see) amino acids with alpha and keto-glutaric to - that under the influence of enzymes of aminotransferases, or transaminases (see. Aminotransferases ), with education L-glutaminic to - you and an a-ketoanalogue of initial amino acid. At interamination of NH 2 - the group is had from amino acid on alpha and keto-glutaric to - that without intermediate release of ammonia. A coenzyme of transaminases is derivative vitamin B 6 — pyridoxal phosphate (see. Coenzymes ). The last carries out a role of a carrier of NH 2 - group and hydrogen atom. In the second reaction of trans-deamination L-glutaminic to - that is deaminized in alpha and keto-glutaric by means of a glutamatdegidrogenaza. The greatest activity of a glutamatdegidrogenaza, the most important enzyme of amino-acid exchange, at the person is concentrated in a liver. Transaminases are present at all living cells of the person, animals, plants, microorganisms.
For the proof of process of the trans-deamination proceeding in tissues of animals researches on the model fermental systems including the purified drugs of transaminases and a glutamatdegidrogenaza and necessary cofactors were conducted. Also the researches conducted with B6 - avitamonous animals, and experiences with use of inhibitors of reactions of interamination and education keto-glutaric to - you in cells were of great importance. These researches confirmed that transdeamination plays a preferential role in an oxidative breakdown of amino acids at mammals.
leads This type of D. of amino acids to formation of alpha oxyacids according to the overall equation 4:
Hydrolytic D. is revealed at mold mushrooms and some bacteria. Formation of oxyacids at animals was observed at massive loadings amino acids. The enzymes catalyzing this process are not known. Most of authors considers that alpha oxyacids represent products of secondary enzymatic recovery of ketonic acids or hydration unsaturated to - t. formed of amino acids as a result of their oxidizing or intramolecular. By direct enzymic hydrolysis there is D. of the purine and pirimidinovy bases (see. Pirimidinovy bases , Purine bases ), nucleosides and nucleotides with the participation of hydrolases purine - and pirimidindezaminaz. The last are rather specific and unevenly widespread in the nature. Some of them are received in the cleared and crystal look and well studied. Of adenine (see. Purine exchange) proceeds with education hypoxanthine (see) with the participation of an adeninedeaminase (KF 126.96.36.199). This enzyme is not found in the highest animals and the person; it is found at insects, Crustacea, at plants and bacteria. Of guanine in xanthine (see) occurs at action of a guanindezaminaza (KF 3. 5.4.3). High activity of this enzyme is found in a brain and in erythrocytes of rats. In the similar way D. of nucleosides of adenine and guanine with the participation of an adenosinedeaminase proceeds (KF 188.8.131.52.), eurysynusic enzyme in the nature, and a guanazindezaminaza, the enzyme found at microorganisms (pseudo-monads), but not found in animals. Adenylic to - you (see. Adenozinfosforny acids ) it is most well studied; enzyme the AMF-deaminase (KF 184.108.40.206) is present at large numbers in skeletal muscles of the person and animals and is practically absent in unstriated muscles; it is found at plants and bacteria. Enzyme is received in a crystal look, contains SH groups and ions of Zn 2+ . Irreversible reaction of D. adenylic to - you proceeds with formation of inosinic acid (see. Inosinic acids ). In tissues of animals, the enzyme of a tsitozindezaminaz (KF 220.127.116.11) turning tsitozin is found in yeast and bacteria (see. Pirimidinovy bases ) in uridine (see). D. of cytidine and cytidylic to - you, and also dezoksitsitidilovy to - you is described by the corresponding dezaminaza.
This type of D. is widespread among some sporiferous anaerobic bacteria from the Clostridium family and is known under the name of «Stiklend's reaction». Process proceeds according to the overall equation 5:
Recovery D.'s mechanism consists in the interfaced anaerobic redoxreaction between two amino acids from which one acts as hydrogen donator, and another — as his acceptor. As a result both amino acids are deaminized. E.g., reaction between alanine (donor) and glycine (acceptor) consists schematically of the following transformations:
Similar reactions observed between other vapors of amino acids. As reaction products of proline it is formed delta and aminovalerian to - that, of an isoleucine, a leucine, valine — alpha-methylbutyric, isovalerianic and isobutyric respectively. The enzymes participating in this type of D. are a little studied; the mechanism of this process needs specification.
Process proceeds with education unsaturated to - you according to the overall equation 6:
Plants and some bacteria have in such way D. L-asparaginic to - you by means of eurysynusic aspartate-ammiakliazy (KF 18.104.22.168; former name «aspartaz»); as a result from L-asparaginic to - you are formed fumaric to - that and ammonia. Reaction is reversible. Enzyme was cleared and studied; it contains ions of Mg 2+ and SH groups. In a liver of the person and animals in the similar way there is D. of a L-histidine enzyme histidine-ammonia-lyase (KF 22.214.171.124). Gistidin (see) it is irreversible it is deaminized in a beta imidazolilakrilovuyu (urocanic) to - that. Some bacteria have similar D. of other amino acids (e.g., aromatic).
Some beta and gamma hydroxy-amino acids (serine, threonine) and mercaptoamino acids (cysteine, methionine) are deaminized in the special ways with the participation of specific enzymes.
Definition of activity of the enzymes catalyzing different types of deamination
Definition of activity of the enzymes catalyzing different types of deamination is additional diagnostic test at a number of diseases. Disturbance of processes of D. in a liver and other bodies and tissues of the person and animals is connected with change of activity of the enzymes catalyzing D.'s processes and interaminations. At the diseases connected with proteinaceous insufficiency reduction of activity of the enzymes catalyzing oxidizing D. and interamination is observed. The most popular and widely applicable method of an enzimodiagnostika in laboratories and clinics is definition of activity aspartate - (KF 126.96.36.199) and alanine - (KF 188.8.131.52) of aminotransferases (ASAT and ALAT) respectively. The largest content of ASAT is revealed in a cardiac muscle, then (in the decreasing order) in a liver, skeletal muscles, a brain, kidneys, seed plants. The greatest activity of ALAT is revealed in a liver, a pancreas, heart and skeletal muscles.
Activity of both enzymes in blood serum increases at the diseases proceeding with a necrosis and damage of fabrics, hl. obr. cardiac muscle and liver. Activity of ASAT most sharply increases at a myocardial infarction, usually in proportion to the size of the site of a necrosis.
At diseases of a liver first of all and considerably activity of ALAT increases. Especially sharply it increases at a viral hepatitis (at most on 6 — the 11th day of a disease), and activity of ALAT increases already in an incubation interval that has great diagnostic value. Activity of ASAT and ALAT increases and at metastasises of cancer in a liver; at mechanical jaundices of increase in activity of aminotransferases in blood serum did not note. In laboratory diagnosis use the size of the relation of activity of ASAT to ALAT. At healthy people the size of this coefficient is equal to 1,33±0,42; at patients with an acute viral hepatitis — 0,65, at a myocardial infarction the size of coefficient sharply exceeds normal. Hyper aminotransferasemias are noted also at hemolitic anemias, pancreatitis, poisonings and so forth.
Normal activity of ASAT and ALAT fluctuates from 0,005 to 0,0182 and from 0,0028 to 0,0186 mkmoly substrates, the split 1 ml of blood serum in 1 min.
See also Nitrogen metabolism .
Bibliography: Berezov T. T. Exchange of amino acids of normal fabrics and malignant tumors, M., 1969, bibliogr.; Braunstein A. E. Biochemistry of amino-acid exchange, M., 1949, bibliogr.; it, Highways of assimilation and dissimilation of nitrogen at animals, M., 1957, bibliogr.; M e i s t e of A. Biochemistry of the amino acids, v. 1—2, N. Y. — L., 1965, bibliogr.; Sallach H. J. a. F a-hien L. A. Nitrogen metabolism of amino acids, in book: Metabolic pathways, ed. by D. M» Greenberg, v. 3, p. 1, N. Y. — L., 1969, bibliogr.; Tabor C. W. a. T a b about of H. 1,4-diaminobutane (putrescine), spermidine, and spermine, Ann. Rev. Biochem., v. 45, p. 285, 1976, bibliogr.
E. F. Efimochkina.