TRANSAMINYROVANIE (a synonym interamination) — reversible intermolecular transfer of an amino group (GSh2-group) together with a proton and couple of electrons from amino acids or amines to oxoacids or other carbonyl compounds (aldehydes, ketones).
T. occurs according to the following schematic diagram:
T. is the process having extremely big obshchebiol. value. Definition of activity, studying of properties of the enzymes catalyzing reactions of T., a research of patterns of these reactions play an essential role in interpretation of a pathogeny, and also in klini-to-biochemical diagnosis and forecasting of a course of nek-ry diseases. Genetically determined defect of the nek-ry enzymes participating in T., is the reason of a number of hereditary diseases (see Enzymopathies).
Enzymatic T. it was opened in 1937 by the Soviet biochemists A. E. Braunstein and M. G. Krits-man. Investigating transformations of L - glu-taminovoy to - you in skeletal muscles and a myocardium, they established bystry movement of its NH2 rpynnbi on pyroracemic (and - oxopropionic) to - that with education and - oksogluta-rovoy to - you and L-alanine; reaction so easily went in the opposite direction (to a certain equilibrium point). In this system the NH2 group of a glutamate was accepted also by nek-ry others and - oxoacids.
At biological, enzymatic, T. the most often initial substrates are and - amino-KI to * lots (see Amino acids) and and - oxoacids (see Ketonic acids). Position of balance in enzymatic reactions of T. Pervonachalno depends on a structure of their molecules assumed that in biol. T. dicarbonic amino acid and oxo-acid (preferential couple a glutamate — oxoglutarate) shall be one of substrate couples. Further existence in cells of any organisms of reactions of T was established. between monocarboxylic donors and acceptors of NH2 rpynn without participation aminodicarbonic to - t. Later existence of the fermental systems operating on substrates from NH2-and respectively WITH - groups not in and - polozhe-npi was revealed, an in r-, at - or 6 situation. In reactions of T. and-aminokiyelot at the person, animals and plants only L-isomers participate, and in cells of these eukaryotic organisms donor-acceptor couple a L-glutamate — and - oxoglutarate is the most actively turned usually.
By Thorne (S. V. of Thorne) the transamnnnrovaniye of D-isomers of amino acids at microorganisms, in particular at bacilli was opened; by this way D-aminoknslotnye the remains which are contained in a cell wall of microorganisms are formed.
The enzymes catalyzing reactions Transaminum and a ditch and N and I Reactions of T. catalyze enzymes of an aminotraneferaza, or transaminase (see Aminotraneferaza). It is known apprx. 60 individual, differing on substrate specificity aminotransferases combined in the Nomenclature of enzymes under the code code of KF 2.6.1..., apart from multiple forms of these enzymes specific in the specific relation and various on intracellular localization (e.g., mitochondrial and cytoplasmatic) and separate physical. and to chemical signs (see Isoenzymes). One aminotraneferaza have strict substrate specificity to certain donor-acceptor couples, substrate specificity of others is relative and directed to group of related substrate couples containing, e.g., aromatic cycles in (3 situation; at the same time this or that substrate can have especially high affinity to enzyme. So, the aminotraneferaza catalyzing transfer of wasps - 5sh2 - groups of a glutamine or asparagine, have to the corresponding amide bigger affinity, than to other NH2 donor is considerable (wasps-amino-monocarboxylic to - there).
Aminotraneferaza are among enzymes, the molecule to-rykh consists of protein (apoenzyme) defining substrate specificity and type of the catalyzed reaction, and a cofactor, or prosthetic group (see Coenzymes) — in this case pyridoxal phosphate (see) — derivative rat anti-acrodynia factor (see the Pyridoxine). In the 40th 20 century were shown that at insufficiency of polyneuramin 6 at animal and nek-ry bacteria activity of aminotransferases in cells decreases, and it can be recovered addition to acellular extracts of phosphoric ether piridoksalya. For the first time in the late fifties in the form of almost pure, individual protein from a cardiac muscle of pigs emitted 20 century aspartate aminotransferase (glutamate-aspartate-transaminase; KF 22.214.171.124). It was succeeded to separate a cofactor from an apoenzyme and accession to the last synthetic piridoksal-5' - phosphate to regenerate active aminotransferase; similar results were received for all studied specific aminotransferases later. Physical are studied most in detail. and chemical properties, and also catalytic effect of aspartate aminotransferase of a myocardium and aspartate aminotransferases from other biol. sources. In laboratories A. E. Brown matte, Yu. A. Ovchinnikova, Snella (E. E. Snell) and in nek-ry others are established primary and tertiary structures of a molecule of this enzyme, its optical and others physical. properties and the main chemical stages of the reaction catalyzed by it.
The mechanism enzymatic to trances and niro-in and N and I. In reaction of T. pyridoxal phosphate plays a role of a carrier of NH2 rpynn. The nature of intermediate reactions, from to-rykh develops process of transfer, is found out by A. E. Braunstein and Snell. Process proceeds according to the following scheme presented in a little simplified form (the symbol 0 = Sn*rug designated a proteid of pyridoxal phosphate, R1 and R2 is the corresponding radicals):
In the offered scheme the condition of ionization of carboxyl groups (SOON-group) and nitrogen atoms is not considered, and also the fact that in a molecule of enzyme pyridoxal phosphate is not in a free form, and in the form of an imine of £ - 1\tn2-group of the rest of a lysine of fermental protein.
In the first semi-reaction (la) the NH2 group of amino acid is transferred
to aldehydic group of aminotransferase by education and a regrouping of imines (the shiffovy bases) with formation of ketonic acid and a proteid piridoksaminfosfa-that. The last in the second polureak-tion (16) reacts on the same type with other oxoacid, forming new amino acid and an initial proteid of pyridoxal phosphate.
A role Transaminum and a ditch and N and I in an energy and nitrogen metabolism. In vegetable and animal fabrics reactions of T are most active., at to-rykh 1\tn2-group are transferred on three formed in processes of glycolysis (see) and tissue respiration (see biological oxidation) and - oxoacids: pyroracemic, shcha
velevo-acetum and and - oksogluta-rovuyu (and in the opposite direction — from three corresponding and)))))))))))))). One of important fiziol. functions T. consists in interconversions of these six metabolites and regulation of glycolysis and tissue respiration by elimination or formation of intermediate oxoacids, and thereby — in regulation of formation of carbon skeletons of amino acids and their uses in processes of full oxidation, a gluconeogenesis (see Glucose, Carbohydrate metabolism) or a ketogenesis (see. Ketone bodies) without the accompanying loss of amine nitrogen, valuable to an organism. Of the same name, but differently localized in a cell (e.g., in cytosol and in mitochondrions) aminotransferases play unequal roles in fabric exchange. It is established that any states demanding urgent mobilization of components of protein for a covering of a metabolic cost of an organism (such as insufficient or unbalanced food, all types of a stress), are connected with adaptive, hormonal and stimulated biosynthesis of the certain aminotransferases in particular participating in a gluconeogenesis (alanine - and aspartate aminotransferases, aminotransferases of aromatic amino acids).
In tissues of the person and other mammal NH2 rpynnbi of natural amino acids, except L - glutamino-howl, are unavailable or difficult give in to direct dissimilation by oxidizing deamination (see), as well as to synthesis by means of direct amination of oxoacids. Opening of T. on the first time led to emergence of a hypothesis, later comprehensively reasonable, about dominance indirect, mediated through T. with oksoglu-taraty — a glutamate ways of deamination and according to synthesis of the majority of amino acids (except a glutamate). It was shown that these processes are suppressed in rie-rezhivayushchy fabrics and in vivo with all influences, to-rye break reactions of T. (a hypovitaminosis of B6, inhibitors of aminotransferases) or separate modes of formation and - oxoacids in a cycle tricarboxylic to - t (see. Tricarboxylic acids a cycle), are also recovered at compensation of the blocked reaction. The glutamate which is formed during indirect deamination or is oxidized glutamatdegidrogenazy to ammonia, or his NHo-grugsha passes by T. and other enzymatic turning into the list of L - ac-partata, glycine, a glutamine and various nitrogenous compounds representing the closest sources of nitrogen in processes of mochevino-education (see Urea), synthesis of purines (see. Purine bases), pyrimidines (see the Pirimidinovy bases), uric acid (see) and other important nitrogen-containing metabolites (see. Nitrogen metabolism).
Value of a research of t r and N with and m and N and r about in An and I for to l and N and h e with to about y m e d and c and and z. Receipt in blood of certain aminotransferases from fabrics (a myocardium and skeletal muscles, a liver, etc.) allows to distinguish patol. the states which are followed by necrobiotic changes and to estimate extent of such changes. So, at the acute coronary insufficiency which is followed by a myocardial infarction (see) unlike an attack of stenocardia (see) activity of aspartate aminotransferase in blood serum of the patient sharply increases (by 5 — 10 times in the first
2 days after developing of a heart attack), and then gradually decreases, reaching usually norm for the 5th day. Repeated rise in activity of enzyme indicates expansion of the site of a necrobiosis of a myocardium (or emergence of new) that predictively is adverse. Activity of alaninaminotranspherase in blood serum at a myocardial infarction increases only slightly (obviously, owing to rather small content of this enzyme in a myocardium). Destructive defeats of skeletal muscles (at injuries, a thrombembolia, a caisson disease and ischemia, etc.) are followed by receipt in blood both aspartate - and alaninaminotranspherases.
Substantial increase of activity of these two and nek-ry other aminotransferases in blood of the patient matters at the differential diagnosis of the defeats of a parenchyma of a liver which are followed by jaundice: aminotransferases come to a blood plasma from tissue of a liver at infectious hepatitis (see a viral hepatitis), but not in case of mechanical jaundice, e.g., at cholelithiasis (see).
A number of rather rare hereditary diseases is known, to-rykh genetically caused defect of biosynthesis of these or those proteins-enzymes, in particular is the cornerstone of nek-ry aminotransferases. The pathogeny of a peculiar form of the progressing ring-shaped dystrophy of a choroid and a retina of an eye (horioretinopatiya) which is usually bringing in youthful age to almost total blindness is deciphered. The group of the Finnish clinical physicians found sharply expressed ornitinemiya in these patients. Inborn defect of biosynthesis ornithine-oxo-acid — aminotransferases (KF 126.96.36.199) was the reason of accumulation in blood and fabrics of ornithine. Further it was established that ornithine, in turn, suppresses important enzymatic reaction, the cut is one of products this amino acid; namely transfer of guanidinovy group of arginine on glycine with education guanidineacetic to - you. This connection — the immediate biosynthetic precursor of creatine (see) and, further, creatine phosphate. The described cascade of biochemical disturbances leads to essential suppression of synthesis of creatine phosphate; cells of the visual analyzer were especially sensitive to such insufficiency of power providing their trophicity. Suppression of activity of aminobutyrate-amino-transferase (transaminase at-amino-oil to - you; KF 188.8.131.52) at a hypovitaminosis of B6 or owing to genetic defect is one of the most important reasons of overweight of processes of braking in a brain over processes of the excitement observed at these states.
Bibliography: Braunstein A. E.
Highways of assimilation and dissimilation of nitrogen at animals, M., 1957; Braunstein A. E. and Shemyakin M. M. The theory of the processes of amino-acid exchange catalyzed by piridok-salevy enzymes, Biochemistry, t. 18, century 4, page 393, 1953; The Nomenclature of enzymes, the lane with English, under the editorship of A. E. Braun matte, M., 1979; About in the h and N of N and to about in Yu. And., etc. Full primary structure of aspartate aminotransferase, Dokl. Academy of Sciences of the USSR, t. 207, No. 3, page 728, 1972; Braun-stein A. E. Amino group transfer, in book: The enzymes, ed. by P. D. Boyer, v. 9, p. 379, N. Y. — L., 1973;
Mei-ster A. Biochemistry of the amino acids, v. 1—2, N. Y. — L., 1965; Thorne C.B. Transamination of D-amino acids, in book: A symposium on amino acid metabolism, ed. by W. D. McElroy a. H. B. Glass, p. 41, Baltimore, 1955. A. B. Braunstein.