[Physiological significance of amine oxidases and technique for determination of their activity].

The paper describes the physiological effects of various biogenic amines, their occurrence in the body, and degradation. It outlines the present views of diversity of flavin adenine dinucleotide-dependent and semicarbazide-sensitive amine oxidases. Methods for preparation of various tissue extracts and spectrophotometric and radiation techniques for determination of the activity of these enzymes, by using various substrates, are described.

[Furin as proprotein convertase and its role in normaland pathological biological processes]. / Furin kak proproteinkonvertaza i ego rol' v normal'nykh i patologicheskikh biologicheskikh protsessakh.

Furin belongs to serine intracellular Ca2+-dependent endopeptidases of the subtilisin family, also known as proprotein convertase (PC). Human furin is synthesized as zymogen with a molecular weight of 104 kDà, which is then activated by autocatalytic in two stages. This process can occur when zymogen migrates from the endoplasmic reticulum to the Golgi apparatus, where a large part of furin is accumulated. The molecular weigh t of the active furin is 98 kDà. Furin relates to enzymes with a narrow substrate specificity: it hydrolyzes peptide bonds at the site of paired basic amino acids and furin activity exhibits in a wide pH range 5-8. Its main biological function is activation of the functionally important protein precursors. It is accompanied by the launch of a cascade of reactions, which lead to appearance of biologically active molecules involved in realization of specific biological functions both in normal and in some patologicheskih processes. Furin substrates are biologically important proteins such as enzymes, hormones, growth factors and differentiation, receptors, adhesion proteins, proteins of blood plasma. Furin plays an important role in the development of processes such as proliferation, invasion, cell migration, survival, maintenance of homeostasis, embryogenesis, as well as the development of a number of pathologies, including cardiovascular, oncologic and neurodegenerative diseases. Furin and furin-like proprotein convertases participate as key factors in the realization of the regulatory functions of proteolytic enzymes, the value of which is currently being evaluated as most important in comparison with the degradative function of proteases.

Main ethanol metabolizing alcohol dehydrogenases (ADH I and ADH IV): biochemical functions and the physiological manifestation.

The range of the biochemical reactions which can be catalyzed by ADH I and ADH IV is extremely wide. The most characterized functions of these enzymes are protection against excess endogenous acetaldehyde, products of lipid peroxidation, exogenous alcohols and some xenobiotics. It was found also that ADH I and ADH IV are important members of the enzyme system synthesizing retinoic acid (especially during embryogenesis). They can oxidize some steroids and participate in bioamine and prostaglandin metabolism but so far the extent of their contribution to the latter processes is under discussion. Recent data suggest a correlation between the activity of ADH I in some organs and fine physiological processes including behavior regulation and craving for alcohol in albino rats.

Monoamine oxidase inhibition by novel antidepressant tetrindole.

The novel antidepressant tetrindole (2,3,3a,4,5,6-hexahydro-8-cyclohexyl-1H[3,2,1-j,k] carbazole) was found to be a selective inhibitor of monoamine oxidase A (MAO A). In vitro it inhibited rat brain mitochondrial MAO A in a competitive manner with Ki value of 0.4 microM. A 60 min preincubation did not change the competitive mode of interaction between enzyme and tetrindole (Ki value was 0.27 microM). The inhibition of rat brain mitochondrial MAO B was of mixed type with Ki value of 110 microM. Dilution or dialysis of mitochondrial suspension did not restore MAO A activity after inhibition by tetrindole both in vitro and in vivo, whereas inhibition of MAO B in vitro was completely reversible. Oral administration of tetrindole inhibited rat brain and liver mitochondrial MAO A by 80% within 0.5-1 hr and the onset of recovery of enzyme activity became evident after 24 hr. A small inhibition of MAO B (-20-30%) was observed in isolated brain and liver mitochondria within 1-6 hr and enzyme activity had completely recovered after 16 hr. The data obtained indicate that antidepressant activity of tetrindole may be explained by selective inhibition of MAO A, however an apparent discrepancy between competitive manner of MAO A inhibition in vitro and poor recovery of enzyme activity in vivo does not allow us to decide whether tetrindole is a "tight-binding" reversible inhibitor or a selective irreversible inhibitor of MAO A.

Modulation of glutamate neurotoxicity in the transformed cell culture by monoamine oxidase inhibitors, clorgyline and deprenyl.

Addition of 30mM glutamate to the culture medium decreased growth of rat glioma C6 cells accompanied by a decrease of DNA synthesis and an increase of lactate dehydrogenase (LDH) detected in the conditioned medium. The presence of 1 microM deprenyl attenuated the glutamate effect on cell growth only during the first 24-48 h incubation and had a minor influence on the glutamate-induced decrease of DNA synthesis. Clorgyline (1 microM) potentiated glutamate-induced DNA synthesis during the first 24 h incubation without significant influence on the cell growth. Deprenyl slightly attenuated the glutamate-induced LDH increase during 24 h incubation but potentiated the glutamate effect at 96 h. Clorgyline decreased the glutamate influence at 24 h and especially 96 h. All these effects were observed in the absence of exogenous monoamines in the culture medium. These results suggest that in transformed cells monoamine oxidase (MAO) inhibitors may influence processes of cell death via MAO-independent mechanisms.

[Medico-biological aspects of biochemistry of amines and other nitrogen bases]. / Mediko-biologicheskie aspekty biokhimii aminov i drugikh azotistykh osnovanii.

The art-of-the-state and possible perspectives for studies of the properties of amine oxidases which are medically significant are briefly outlined. Due to the studies conducted at the Research Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences, the authors discuss the results of studies of the following three problems: 1) modified catalytic properties of amine oxidases in experimental intoxications and abnormalities; 2) natural modulators of amine oxidases; 3) synthetic modulators of amine oxidases.

[Correlation of chronic idiopathic headache and decreased monoamine/oxidase activity of thrombocytes]. / O sviazi khronicheskoi idiopaticheskoi golovnoi boli so snizheniem aktivnosti monoaminoksidazy trombotsitov.

A total of 19 males with chronic idiopathic headache referred to in the literature as tension headache were examined. A secondary nature of headache was completely ruled out by additional studies. The activity of platelet monoamine oxidase was depressed to 14.33 +/- 1.17 n mol/mg of protein/h as compared with 28.1 +/- 2.38 n mol/mg of protein/h in the control group. The role of diminished activity of the enzyme in the genesis of headaches is considered.

[Use of bacterial luciferase for determining monoamine oxidase activity]. / Ispol'zovanie bakterial'noi liutsiferazy dlia opredeleniia monoaminooksidaznoi aktivnosti.

A bioluminescence assay is proposed for measuring monoamine oxidase activity in different biological specimens (platelets, mitochondria). The assay is based on the bioluminescent reaction catalysed by bacterial luciferase and coupled to monoamine oxidase. Two modifications of the bioluminescence assay were used. In the first case, the bioluminescent system was added to monoamine oxidase preincubated with the substrates, while in the second case, all the components of the coupled enzymatic systems were directly mixed in a cell. The proposed bioluminescence assay is simple, highly sensitive and rapid, and could be especially useful for biomedical examinations.

[Cytosol monoamine oxidase in the rat liver]. / Issledovanie tsitozol'noi monoaminoksidazy pecheni krys.

Cytosolic and particulate monoamine oxidases have been isolated. Cytosolic preparation was free from mitochondrial and microsomal contaminations and also ribosome-bound MAO molecules. Cytosolic MAO had higher affinity for phenylethylamine and exhibited higher sensitivity to acetylenic inhibitors than the mitochondrial enzyme.

[Multiple forms of human brain monoamine oxidase]. / Mnozhestvennye formy monoaminoksidazy mozga cheloveka.

Treatment of normal human brain mitochondria with a mixture containing Triton X-100 and urea resulted in solubilization of monoamine oxidase (MAO) exhibiting tyramine-, serotonine-, phenylethylamine- and dopamine deaminase activities at ratios similar to those characteristic for the initial mitochondria. A purified preparation of the enzyme was obtained after AH-Sepharose chromatography; it was shown that in the brain there were present four isoenzymes of MAO possessing different substrate specificity. Investigation of some properties of MAO (activity, solubilization and isozyme composition) from brain regions showed absence of asymmetry and higher enzymatic activity in the subcortical brain region as compared with right and left brain cortex.

[Selective inhibition of monoamine oxidase in bovine brain by befol and moclobemide]. / Ob izbiratel'nosti tormozheniia monoaksidazy mozga byka befolom i moklobemidom.

Effects of befol and moklobemide on thyramine-, serotonin- and 2-phenyl ethylamine deaminase activities of mitochondrial monoamine oxidase from bovine truncus cerebri were studied. These drugs are reversible noncompetitive inhibitors of the enzyme not requiring preincubation. They inhibited most effectively the serotonin deaminase activity as compared with phenyl ethylamine deaminase activity, however they should not be concerned with typical inhibitors of monoamine oxidases of the A type as inhibition of thyramine deaminase activity was not found.

[Defect in the properties of brain mitochondrial monoamine oxidase in schizophrenia]. / O narusheniiakh svoistv mitokhondrial'noi monoaminoksidazy mozga pri shizofrenii.

A highly purified individual form of monoamine oxidase (MAO-11b) has been isolated by means of affinity chromatography on AH-Sepharose 4B after solubilization of biomembranes from schizophrenic or normal brain tissues. The enzyme preparations obtained catalyzed deamination (both in schizophrenia and normal state) not only of serotonin and 2-phenylethylamine but also of histamine and contained about 2 SH-groups per 10(5) dalton of protein which is characteristic for "transformed" MAO with partially oxidized SH-groups. Preincubation of MAO-11b from normal brain with 10 mM dithiothreitol caused "re-transformation" of MAO: there was a marked decrease in histamine deaminating activity with simultaneous increase in the MAO activity and in content of SH-groups. In schizophrenia the re-transformation of MAO was impaired: preincubation of MAO-11b under the same conditions led to an increase in content of SH-groups and in MAO activity but the preincubation with a reducing agent did not decrease (causing, to the contrary, a marked increase) the deamination of histamine.

[Kinetic properties of monoamine oxidase isoenzymes from the bovine brain]. / Kineticheskie svoistva mnozhestvennykh form monoaminoksidazy mozga byka.

Multiple forms of monoamine oxidase (MAO I, IIa, IIb, III) from bovine brain, separated by means of affinity chromatography on AH-Sepharose 4B, were dissimilar in kinetics of deamination of serotonin and beta-phenylethylamine used as substrates of the MAO of A and B types. MAO-I catalyzed the deamination of beta-phenyl ethylamine and serotonin. Km and Vmax values could not be calculated for MAO-IIa since the rate of enzymatic reactions was characterized by a complicated dependence on concentration of serotonin in a sample. MAO-IIb catalyzed also the deamination of both AMO substrates.

[Changes in substrate specificity of brain mitochondrial monoamine oxidase]. / Issledovanie izmenenii substratnoi spetsifichnosti monoaminoksidazy mitokhondrii mozga.

Mitochondrial monoamine oxidase isolated from bovine brain stem and purified to electrophoretic homogeneity contained 15 SH groups per mole (100000) of protein. The enzyme deaminated tyramine, p-nitro-beta-phenylethylamine, dopamine, 5-hydroxytryptamine, tryptamine but did not deaminate histamine, GABA or spermidine. Oxidation of 9-II SH groups in the MAO by air oxygen was accompanied by appearance of the properties to deaminate histamine or GABA. This qualitative alteration (transformation) in catalytic properties of the enzyme was readily reversed by treatment with reducing agents (dithiothreitol or GSH). No structural alterations detectable by electrophoresis in polyacrylamide gel were observed in course of the qualitative reversible modifications in catalytic activity of MAO. The qualitative alterations in substrate specificity were also initiated by treatment with H2O2 of the monoamine oxidases tightly bound with membrane structures of mitochondria from bovine brain stem.

[Mechanisms of suppression of alcohol motivation after immunization of albino rats against alcohol dehydrogenase I: The role of ADH epitopes and ADH activity in the adrenal glands]. / O mekhanizmakh podavleniia alkogol'noi motivatsii pri immunizatsii belykh krys k alkogol'degidrogenaze I: rol' épitopov ADG i aktivnosti ADG v nadpochechnikakh.

Experimental results have demonstrated a significant decrease in the level of alcohol consumption by albino rats immunized with heterologous horse alcohol dehydrogenase. The role of ADH epitopes 9-14, 93-115, and 265-276 in this phenomenon was examined, and it was established that the latter sequence (265-276) plays the biggest role. The inhibition of ADH activity in the adrenals of immunized rats was much higher compared to the liver. We propose a hypothesis that the effect of alcohol dehydrogenase on alcohol consumption is connected with its role in catecholamine metabolism.

[Administration of the omega-3 polyunsaturated fatty acid drug eiferol decreases alcohol motivation in albino rats by elevating the level of antibodies to alcohol dehydrogenase]. / Vvedenie preparata polinenasyshchennykh zhirnykh kislot semeistva omega-3 (éiferola) snizhaet alkogol'nuiu motivatsiiu u belykh krys, povyshaia uroven' antitel k alkogol'degidrogenaze.

The study experimentally assessed the approach proposed by the authors to lower alcohol motivation, which involves enhancement of a specific immunity at the stage of alcoholization when acetaldehydemodified ethanol exchange enzymes [alcohol dehydrogenase (ADH)] and acetaldehyde dehydrogenase may be expected to occur. Omega-3 polyunsaturated fatty acid (PUFA) drugs enhance the formation of autoantibodies to modified ADH and decrease the activity of ADH in the stomach and liver. At the same time, PUFA drugs can, under certain conditions, produce an anti-alcoholic activity and a positive effect on the psychoemotional status of animals after the ethanol deprivation period.

[Disturbance of monoaminooxidase activity and indices of endogenous intoxication in patients with the first episode of schizophrenia].

An aim of the paper was to study some biochemical parameters of drug-naïve patients with the first episode of schizophrenia. Activities of platelet monoaminooxidase (MAO) and semicarbazide, a sensitive blood serum aminooxidase (BSA), levels of middle-sized molecules (MSM) and malonic dialdehyde (MDA), parameters of functional state of serum albumin were assessed in 16 patients. Severity of symptoms in patients with the first episode of schizophrenia was assessed as moderate (PANSS scores 73.1+/-12.5) before the treatment. The increase of MAO by 107%, reduction of BSA by 29% and increase of MSM level by 140% was found in patients compared to controls (p<0.01). The study of other biochemical (MDA level) and biophysical (effective albumin concentration) parameters did not yield unequivocal results. It has been suggested that MAO and BSA are integral components of pathogenetic mechanisms in patients with the first episode of schizophrenia.