INHIBITORS (Latin inhibere to stop, hold) — the substances of the various chemical nature which are braking or completely oppressing the speed of chemical, physical and chemical and biological processes; find application in medicine as pharmaceuticals, activity of some inhibitors in blood serum is additional diagnostic test at a number of diseases; in the national economy are used in fight against agricultural wreckers; many inhibitors are toxic agents.
And. chemical processes slow down oxidation reactions of lubricating oils, metallic corrosion, oxidation of different types of fuel, stop or completely prevent polymerization process other. And. processes various chemical connections which sharply reduce the speed of chain reactions since at collision with the free radical I who is formed in such reaction are biophysical. in turn the low-active radicals which are not promoting development of chain process form. And. growth of plants the substances which are braking or completely oppressing germinations of seeds, growth of a stalk, blooming of kidneys, etc. are.
In biochemical, literature the term «inhibitor» most often is called the substance in whole or in part oppressing enzymatic process. Sometimes these substances are called still fermental or protoplasmatic poisons, to the Crimea cyanides, carbon monoxide, salts of heavy metals, etc. belong, e.g. Enzymatic processes are the cornerstone of life activity micro and macroorganisms therefore various substances, overwhelming defined fiziol, functions or biol, processes, carry also to the category I. Are that, e.g., And. growth of some microorganisms (number of amino acids and their derivatives), And. reproductions of viruses (aminopterines, thiouracil, etc.), And. mitotic division of cells (beta galoidalkilaminy), And. blood coagulations (anticoagulants), toxic agents and so forth.
Cases, when And. enzymatic process selectively oppresses only enzyme is uniform, are very rare. Most often And. affect certain centers of enzyme, and in them — specific functional groups — SH groups (so-called sulphhydryl poisons), NH 2 - groups, etc. N-hlormerkuribenzoat, iodacetamide, N-etilmaleimid, yodozobenzoat, arsenite, ferricyanide belong to selective sulphhydryl poisons.
And. specifically contact the activated, coenzymatical or substrate centers on a molecule of enzyme, depriving enzyme of an opportunity to show the activity. Row I. specifically contacts imidazolny group or the rest of serine in an active center of enzyme (e.g., diizopropilftorfosfat). The substances which are nonspecific adsorbed on the surfaces of fermental protein denaturing it or hydrolytic it splitting can have an inhibiting effect on enzyme. Some And., possessing ability to form inner-complex (chelate) compounds, take from a molecule of a choloenzyme (actually enzyme — the apoenzyme connected with a coenzyme) the ion of metal, without to-rogo enzyme cannot show the activity. To it And. belong EDTA (ethylene diamine tetraacetate), etc.
And. phosphorylases (KF 126.96.36.199.) are acetylcholine, karbakhol which action is in turn inhibited by atropine.
Hexokinase (see) it is inhibited by adrenaline and, perhaps, glucocorticoids.
Monoiodacetate, inhibiting a glitseraldegidfosfatdegidrogenaza (KF 188.8.131.52; 184.108.40.206 and 220.127.116.11) glycolysis at a stage of reaction of oxidoreduction oppresses (see. Glycolysis ), and sodium fluoride, And. phosphopyruvate-hydratase (KF 18.104.22.168), inhibits glycolysis after a stage of phosphorylation.
Enzyme of a cycle Tricarboxylic to - t (see. Tricarboxylic acids cycle ) — the succinatedehydrogenase (KF 22.214.171.124) is inhibited by malonate, and the introduction atsetil-KOA in a cycle is blocked ftoratsetaty.
Tsitokhroma (see) are inhibited by cyanide; antimitsin And yes amytal are And., blocking a respiratory chain: the first — between tsitokhroma of b and c1 second — between NAD-N 2 and yellow enzymes. Dinitrophenol separates oxidation and phosphorylation, inhibiting the last.
Enzymes of a pentozny cycle are inhibited by salts of heavy metals which, as well as uabain, are And. and ATP-ases (KF 126.96.36.199. and 188.8.131.52).
In a human body and animals are available And. an endogenous origin which action is opposite to operation of numerous activators i.e. has regulatory character. Treats such regulators acetylcholine (see), regulating activity of cholineacetyltransferase (KF 2. 3. 1. 6), the enzyme participating in synthesis of acetylcholine providing rhythmic reductions of heart. At irritation of a vagus nerve it is released ekstraatsetilkholin which inhibits cholineacetyltransferase as a feed-back, i.e. enzyme is inhibited by reaction product. A phenomenon of a cardiac standstill at irritation and. vagus is explained, thus, by action And. Thanking And. trypsin and pepsin ferruterous cells of a stomach are protected from effect of the proteolytic enzymes produced by them.
More and more widely And. various enzymes are used as pharmaceuticals.
At treatment of acute pancreatitis apply inhibitor of trypsin and chymotrypsin — Trasylolum (see). KOA inhibitors alpha and phenyl-butyric to - that and its amide (Hiposterolum, artosklerol) have ability to reduce the content of cholesterol in blood of the person. At traumatic shock, acute blood loss, surgical interventions on heart, lungs, a uterus, a prostate gland and other bodies there is an activation of fibrinolitic system. Emission at damage of cells of a fabric plasminogen activator can be one of the main reasons of this phenomenon. Treatment of a fibrinolysis is successful only in that case when the specific therapy directed to blockade of formation of plasmin and inhibition of the existing plasmin is used. Treat such drugs synthetic And. a fibrinolysis ε-aminocaproic to - that to - that to - that (((AKK), the n-aminomethylbenzoic to - that (PAMBK) and trance-4-aminomethylcyclohexanecarboxylic to - that (AMTsGKK). Except these connections, for inhibition of a fibrinolysis use Trasylolum and Contrykal (the polypeptide received from lungs of cattle) which is also applied as medicine to treatment of acute pancreatitis.
In rather large number are present at blood serum of the person And. trypsin, connecting this enzyme at the increased receipt it in blood. Normal values of activity of the general And. in blood serum of the person make from 300 to 600 milliyedinitsa (activity And. express in milliyedinitsa of the inhibited trypsin). At various inflammatory processes activity And. trypsin in blood serum increases up to 1500 — 2000 milliyedinitsa; at severe forms hron, pancreatitis it can decrease to 100 — 150 milliyedinitsa.
And. widely physiology, pharmacology, cytology, genetics, etc. uses in pilot studies in the field of biochemistry.
In practice find broad application And. cholinesterases (see) which are used in the national economy as herbicides, fungicides, pesticides, etc. And. cholinesterases are quaternary ammonium compounds, esters carbamic to - you — carbamates (see. Carbamic connections ) and organophosphorous connections (see). Reaktivatora of cholinesterases found practical application as antidotes at poisoning with organophosphorous connections of animals and the person (see. Antidotes of OV ).
Bibliography: Ashmarin I. P. and L. A Klyucharev. Inhibitors of synthesis of protein, L., 1975, bibliogr.; Biophysics, under the editorship of B. N. Tarusov and O. R. Necklace, M., 1968, bibliogr.; Wolkenstein M. W. Molecular biophysics, page 365, etc., M., 1975, bibliogr.
E. F. Romantsev, N. G. Budkovekaya.