COENZYMES

From Big Medical Encyclopedia

COENZYMES (synonym coenzymes) — the low-molecular organic compounds of a biological origin necessary as additional specific components (cofactors) for implementation of catalytic action of a number of enzymes. Many To. represent derivatives of vitamins. Biol, effect of considerable group of vitamins (group B) is defined by their turning into To. and enzymes in cells of an organism. Attempts (and not unsuccessful) direct use of some were made To. with to lay down. purposes. Difficulties which at the same time arise consist that quantitative determination of content is not always made To. in blood and bodies and even less often activity of the enzymes synthesizing or destroying investigated To is defined., also pathologies are normal. The lack of this or that found at any disease To. usually try to eliminate, entering the corresponding vitamin into an organism. But if systems of the synthesis lacking To are broken., what quite often takes place, that administration of such vitamin loses meaning: the therapeutic effect can be gained only introduction of a missing coenzyme. With to lay down. the purposes apply cocarboxylase (see. Thiamine ), FAD, coenzymatical forms of polyneuramin 12 (see. Cyanocobalamine ) and some other K. V to lay down. purposes K. enter parenterally, but also provided that there is not always a confidence that they can get without splitting to the place of the action (on intracellular Wednesday).

Possessing small a pier. it is powerful, To., unlike biocatalysts of the proteinaceous nature (enzymes), are characterized by heat stability and availability to dialysis. Respiratory chromogens of plants (polyphenols), glutaminic to - that, ornithine, bisfosfat (diphosphates) of glucose and glyceric to - you and other metabolites operating under certain circumstances as cofactors of enzymatic processes of transfer, quite often designate as To. corresponding processes. It is more correct to apply the term «coenzyme» only to connections, biol which function comes down entirely or preferential to their specific participation in operation enzymes (see).

The term «coenzyme» was offered by G. Bertrán in 1897 for designation of function of salts of manganese which he considered a specific cofactor phenol elements (laccases); however now inorganic components of fermental systems cannot be carried to number K. Existence true (organic) To. for the first time English biochemists A. Harden and W. Young in 1904 who showed that from fermental extracts of yeast cells at dialysis the thermostable organic matter necessary for action of the fermental complex catalyzing spirit is removed established fermentation (see). Harden and Young called this auxiliary catalyst of fermentation cozymase; its structure was established in 1936 in laboratories X. Euler - Helpina and O. Warburg almost at the same time.

The mechanism of action To. it is not identical. In many cases they act as intermediate acceptors (carriers) of certain chemical groups (phosphatic, acylic, amine, etc.), hydrogen atoms or electrons. In other cases To. participate in activation of molecules of substrates of enzymatic reactions, forming reactive intermediate compounds with these molecules. In the form of such connections substrates are exposed to certain enzymatic transformations; functions are that glutathione (see) as coenzyme of glyoxalase and dehydrogenase of formaldehyde, KOA — at a row transformation fatty acids (see) and others organic to - t etc.

Typical To. form the fragile strongly dissociated connections with specific proteins (apoenzymes) of soluble enzymes from which they can be easily separated in the way dialysis (see) or gel filtering (see). At many reactions of transfer of the groups proceeding at the interfaced effect of two fermental proteins there is a serial reversible accession to molecules of these proteins of particles To. in two forms — acceptor and donorny (e.g., oxidized and recovered, fosforilirovanny and nefosforilirovanny). The mechanism of reversible hydrogen transfer between a molecule of hydrogen donator (AH2) and a molecule of an acceptor (B) at action of two dehydrogenases (Fa and Fb) is shown in the scheme given below (in a little simplified form) and a coenzyme (To):

Overall reaction:

In a complete cycle of oxidation-reduction process (reaction 1 — 6) the coenzyme of a kodegidrogenaz does not change and does not enter balance of reaction products, i.e. serves as the catalyst. If the consecutive phases of a cycle proceeding everyone with participation of one enzyme are considered (reactions 1 — 3 and 4 — 6), then To and Kon2 act on an equal basis with the molecules AH2, A, B, BN2 as the second substrate. In the same sense distinction between substrates and dissociating To is relative., participating in coupled reactions of transfer of phosphatic, acyl, glikozilny and other groups.

At many two-component enzymes constructed as proteids, the apoenzyme forms the strong, hardly dissociating connection with a nonprotein thermostable component. The nonprotein components of enzymes proteids which are usually called by prosthetic groups (e.g., flavin nucleotides, pyridoxal phosphate, metalloporphyrins), interact with substrate, remaining throughout enzymatic reaction as a part of not split molecule of one proteid. The term «coenzyme» is usually distributed also to chemically interacting with molecules of substrates, strongly connected organic prosthetic groups of enzymes which are difficult for delimiting from easily dissociating To., since between both types of cofactors there are gradations.

In the same way the sharp side cannot carry out between To. and nek-ry intermediate products of a metabolism (metabolites) which in enzymatic processes act as the usual substrates which are exposed in this process to generally irreversible change as necessary auxiliary catalysts at the interfaced enzymatic transformations which these metabolites leave not changed. Metabolites such can serve as intermediate acceptors of these or those groups in the processes of enzymatic transfer proceeding similar to the process which is schematically represented above (e.g., a role of polyphenols as hydrogen carriers in breath of plant cells, a role glutaminic to - you in transfer of amine groups by reactions of transamination, etc.), or in more difficult cyclic transformations with participation of several enzymes (function of ornithine in a cycle of an ureapoiesis can be an example). Kofermentopodobny action of a 1,6-bisfosfoglyukoza has a bit different character, edges serves as a necessary cofactor and at the same time a transtage in the course of intermolecular transfer of the phosphatic remains at interconversion 1 phosphoglucose and 6 phosphoglucose under the influence of phosphoglucomutase when the molecule of a cofactor passes into a molecule of an end product, giving one phosphatic rest to an initial product, from to-rogo at the same time the new molecule of a cofactor is formed. Performs just the same function 2,3-bisfosfoglitserinovy to - that at the interconversion catalyzed by other phosphomutase 2-phosphoglyceric and 3-phosphoglyceric to -

since are very various on a chemical structure. However most often connections of two types occur among them: a) nucleotides and some other organic derivatives phosphoric to - you; b) peptides and their derivatives (e.g., folic to - that, KOA, glutathione). At animals and at many microorganisms for creation of molecules of a row K. connections which are not synthesized by these organisms are necessary and shall be delivered with food, i.e. vitamins (see). Water-soluble vitamins of group B in the majority are a part To., a structure and which functions are known (it belongs to thiamin, Riboflavinum, piridoksalyu, to niacinamide, pantothenic to - those), or can work as active molecules K. (polyneuramin 12 , folic to - that). The same probably concerns also others water - and to fat-soluble vitamins which role in processes biol, a catalysis still is completely not found out.

The major are listed below To. with the instruction like their structure and main types of enzymatic transformations in which they participate. In articles about separate To. more detailed information about their structure and the mechanism of action is given.

Coenzymes of the nucleotide nature. Adenylic ribonucleotides (adenosine-5 '-mono-, di - and trifosforny to - you) participate in numerous reactions of activation and transfer orto-and the pyrophosphatic remains, the remains of amino acids (aminoacyls), coal and sulfuric to - t, and also in some other enzymatic transformations. Similar functions in certain cases are performed by derivatives inosine-5 '-phosphorus and guanine riboside-5' - phosphorus to - t.

Guanylic riboiukleotida (-mono-guanine riboside-5, di - and trifosforny to - you) play a role To. at reactions of transfer of the rest amber to - you (succinyl), biosynthesis of ribonucleoproteins in microsomes, biosynthesis adenylic to - you from inosinic and, perhaps, at transfer of the remains of mannose.

Cytidylic ribonucleotides (cytidine-5 '-phosphorus to - you) at biosynthesis of phosphatides play a role To. transfer of remains O-fosfoetanol of sincaline, O-fosfoetanolamina etc.

Uridilovy ribonucleotides (uridine-5' - phosphorus to - you) perform functions K. in processes of a transglycosylation, i.e. transfer of the remains of monoses (glucose, a galactose, etc.) and their derivatives (the remains of geksozamin, glucuronic to - you, etc.) at biosynthesis of di - and polysaccharides, glyukuronozid, geksozaminid (mucopolysaccharides), and also at activation of the remains of sugars and their derivatives in some other enzymatic processes (e.g., interconversion of glucose and a galactose, etc.).

Nicotinamide adenine dinucleotide (NAD) participates in the reactions of hydrogen transfer, major for cellular exchange, as specific To. numerous dehydrogenases (see).

Nikotinamidadenindinukleotidfosfat (NADF) participates in the reactions of hydrogen transfer, major for cellular exchange, as specific To. some dehydrogenases.

Flavinmononukleotid (FMN) participates in biol, hydrogen transfer as To. (prosthetic group) of some flavin («yellow») oxidizing enzymes.

Flavinadenindinukleotid (FAD) participates in biol, hydrogen transfer as To. (prosthetic group) of the majority of flavin («yellow») oxidizing enzymes.

Coenzyme And (KOA which is got into condition — KoA-SH, a coenzyme of acylation; connection adenozin-Z', 5 '-bisfosfornoy to - you with pantotenil-aminothioethyl alcohol or pantheteine) forms from the remains acetic and others organic to - t monothioesters of the R-SO type — S-KOA where R — the rest organic to - you, and play a role To. in transfer and activation of acid residues as at reactions of acylation (synthesis of acetylcholine, benzaminoacetic to - you, steam rooms bilious to - t, etc.), and at many other enzymatic transformations of acid residues (condensation, oxidoreduction or reversible hydration unsaturated to - t). With the participation of KOA a number of intermediate reactions of cellular respiration, biosynthesis and oxidation fat to - t, synthesis of steroids, terpenes, rubber, etc. proceeds.

Coenzyme of B 12 [KoB 12  ; the synonym cobalamine, the DBK coenzyme, alpha (5,6-dimetilbenzimidazolit) - kobamidtsianid]. It is possible that various biol, functions of polyneuramin 12 , which chemical mechanism is not clear yet, napr, in the course of a hemopoiesis, at biosynthesis of methyl groups, transformations of sulphhydryl groups (SH-group) etc., are caused by its role as To. in the course of biosynthesis of proteins-enzymes.

Other coenzymes containing the phosphatic remains. Diphosphothiaminum serves To. at decarboxylation (simple and oxidizing) pyroracemic, alpha and keto-glutaric and other alpha ketonic acids, and also at reactions of splitting of a carbon chain of fosforilirovanny ketosugars under the influence of special group of enzymes (ketomanholes, transketomanholes, phosphoketomanholes).

Pyridoxal phosphate is condensed with amino acids (and amines) in active intermediate compounds like Schiff bases (see. Schiff of the basis ); is To. (prosthetic group) of enzymes, catalyzing reactions of transamination and decarboxylation, and also many other enzymes which carry out various transformations of amino acids (reaction of splitting, substitution, condensation) playing an important role in cellular exchange.

Coenzymes of the peptide nature. Coenzyme of formylation. Recovered folic to - that and its derivatives containing three or seven remains glutaminic to - you, connected by gamma peptide bonds, play a role To. in an intermediate metabolism so-called one-carbon, or «C1», the remains (formyl, oxymethyl and methyl), participating both in reactions of transfer of these remains, and in their oxidation-reduction interconversions. Formylation and oxymethyl derivatives of H4-folic to - you are «active forms» ant to - you and formaldehyde in processes of biosynthesis and oxidation of methyl groups, in exchange of serine, glycine, a histidine, methionine, purine bases etc.

Glutathione. The recovered glutathione (G-SH) works on type K. at transformation of methyl glyoxal in milk to - that under the influence of glyoxalase, at enzymatic dehydrogenation of formaldehyde, in certain stages biol, oxidations of tyrosine etc. Besides, glutathione (see) plays a large role in protection of various thiol (sulphhydryl) enzymes against an inactivation as a result of oxidation of SH-group or binding by their heavy metals and other SH poisons.

Other coenzymes. Lipoic acid is the second To. dehydrogenases pyroracemic and alpha and keto-glutaric to - t (along with Diphosphothiaminum); at effect of these enzymes the rest lipoic to - you connected by an amide link (WITH — NH) with specific fermental proteins, perform functions of an intermediate acceptor (carrier) of hydrogen and the acylic remains (acetyl, succinyl). Other alleged functions of it To. are insufficiently studied.

Vitamin E (tocopherol), phthiocol (phylloquinone) and products their oxidizing vosstanovitelyiykh transformations or closely related derivatives of n-quinone (ubikhinon, a coenzyme of Q) are considered as To. (hydrogen carriers), participating in certain intermediate reactions of a respiratory oxidizing chain and in interfaced to them respiratory phosphorylation (see). It is established that phylloquinone (phthiocol) plays a role To. in biosynthesis of the remains alpha and carboxyglutaminic to - you, the proteinaceous components of system of a blood coagulation which are molecular composition.

Biotin — the water-soluble vitamin which is carrying out a role To. or prosthetic group as a part of a number of the enzymes catalyzing reactions of a carboxylation — decarboxylation of some organic to - t (pyroracemic, propionic, etc.). These enzymes have a structure of biotinil-proteids in which the acylic rest corresponding to biotin (biotinit) is attached by an amide link to N6 amino group of one of the remains of a lysine of a molecule of protein.

Ascorbic acid serves as the activator of fermental system of oxidation of tyrosine in animal fabrics and some other fermental systems (hydroxylases) at which action in a kernel aromatic and heterocyclic compounds, including the peptide and connected remains of proline at biosynthesis collagen (see) and related proteins, hydroxylic groups are entered. In these systems ascorbic to - that plays a role of the second substrate — the hydrogen donator oxidized by molecular oxygen in parallel with cyclic substrate, but not a role true To. (specific biocatalyst).

See also Adenozinfosforny acids , Ascorbic acid , Lipoic acid , Nicotinamide adenine dinucleotide , Pyridoxal phosphate , Tokoferola , Fillokhinona , Yellow enzymes .



Bibliography: Baldwin E. Fundamentals of dynamic biochemistry, the lane with English, page 55, etc., M., 1949; Vitamins, under the editorship of M. I. Smirnov, M., 1974; D and to with about M.'s N and At e E. Enzymes, the lane with English, M., 1966; Coenzymes, under the editorship of V. A. Yakovlev, M., 1973; Kochetov G. A. to the Tiamino-Vyya enzymes, M., 1978, bibliogr.; Enzymes, under the editorship of A. E. Braunstein, page 147, M., 1964, bibliogr.

A. E. Braunstein.

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