[Furin as proprotein convertase and its role in normaland pathological biological processes].

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.

Aspects of metabolic changes in first-episode drug-naïve schizophrenic patients.

Unlabelled: Aim The aim of the study was to investigate the state of parameters characterising different sites of metabolism and the degree of endogenous intoxication in first-episode drug-naïve schizophrenic [first episode of schizophrenia (FES)] patients. It is hypothesised that the FES is the initial step in the development of pathologically disturbed biochemical status that is characteristic of chronic schizophrenia.

Methods: Platelet monoamine oxidase (MAO) and serum semicarbazide-sensitive amine oxidase (SSAO) activities, serum concentrations of middle-mass endotoxic molecules (MMEM) and malondialdehyde and parameters of the serum albumin functional state were measured in 26 FES patients and 15 age-matched healthy controls.

[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.

[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.

[Synthesis of monoamine oxidase in subcellular structures in normal conditions and in alcoholism].

Seasonal variations of recovery of liver monoamine oxidase activity were studied in different subcellular fractions after administration of a large dose of pargyline in vivo. It was shown that the recovery of cytosolic MAO differs greatly from the membrane bound forms in the rate of reconstitution of its activity upon irreversible inhibition in vivo. Alcoholization leads to a decrease of the rate of recovery of only the membrane-bound but not a cytosolic MAO B forms in rat liver.

[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].

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.

[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].

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.

Different sensitivity of mitochondrial and cytosolic monoamine oxidases to in vivo but not in vitro inhibition by specific irreversible inhibitors.

The sensitivity of mitochondrial and cytosolic monoamine oxidase (MAO) activities to inhibition by specific irreversible inhibitors was investigated. There were no significant differences in the sensitivity of MAO A and MAO B activities of these fractions to selective inhibitors. However, in vivo administration of pargyline caused a much more potent inhibition of cytosolic MAO than the mitochondrial enzymes.

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).

[Cytosol monoamine oxidase in the rat liver].

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.

Inhibition of monoamine oxidase by pirlindole analogues: 3D-QSAR analysis.

A series of pirlindole analogues were tested as inhibitors of monoamine oxidase A and B. Although we did not find strict dependence between 3D-size of molecules and their inhibitory potency, rigid analogues exhibited potent and selective inhibition of MAO-A. They have 3D size limits of 13 angstroms (length) x 7 angstroms (height) x 4.

[The use of alternative sources of electrons in mono-oxygenase reactions catalyzed by cytochrome P450. Physico-chemical methods as factors acting on enzymatic activity of proteins].

Influence of physico-chemical methods on catalytic activities of enzymes, (cytochrome P450 in particular), has been reviewed. Authors discussed the properties of semisynthetic flavohemoproteins based on cytochrome P450. With emphasis on recovery of alternative electron sources for redox enzymes.

Inhibition of monoamine oxidase by pirlindole analogues: 3D-QSAR and CoMFA analysis.

A series of pyrazinocarbazoles, analogues of short acting antidepressant pirlindole (2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazole hydrochloride), were tested as inhibitors of monoamine oxidase A (MAO-A) and B (MAO-B). Rigid analogues exhibited potent and selective inhibition of MAO-A and have size limits (X:Y:Z) of 13.0 x 7.

[Peroxide-dependent oxidation of substrates of polysynthetic flavocytochrome 2B4].

Semisynthetic flavocytochromes, obtained by covalent binding of riboflavins with cytochrome P450 2B4, were able to catalyse H2O2-supported aniline p-hydroxylation, amidopyrine N-demethylation and p-nitroanisole O-dealkylation. Rates of these reactions were considerably higher than the rates of corresponding NAD(P)H-dependent reactions and comparable with H2O2-dependent reactions, catalysed by cytochrome P450. Kinetic parameters (Km and kcat) of hydrogen peroxide-supported oxidation of aniline, amidopyrine and p-nitroanisole in the presence of flavocytochrome 2B4 were determined.

Hydrogen peroxide-supported activities of semisynthetic flavocytochrome 2B4.

Semisynthetic flavocytochromes, obtained by covalent binding of riboflavin with cytochromes P450 2B4, were able to catalyze the H2O2-mediated reactions of aniline p-hydroxylation, aminopyrine N-demethylation and p-nitroanizole' O-dealkylation. The rates of the flavocytochrome-catalyzed, H2O2-supported reactions far exceeded those of the appropriate NADH-dependent reactions and were comparable with the cytochrome P450 2B4-catalyzed, peroxide-mediated reaction rates. The kinetic parameters (kcat, K(m)) for the peroxide-dependent flavocytochrome P450 2B4 reactions were obtained.

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.

[Neurotransmitter changes in amyotrophic lateral sclerosis].

The results of investigation concerning both total and cerebral catecholamine metabolism indices in 78 patients with amyotrophic lateral sclerosis (ALS) are presented. The considerable elevation of both blood and liquor norepinephrine level as well as of blood epinephrine concentration was observed together with acute decrease of platelet MAO B activity. The conclusion was made about the participation of catecholamines in exitotoxic mechanisms of motor neurons systems death which was quite characteristic for ALS development.

Interaction of indole derivatives with monoamine oxidase A and B. Studies on the structure-inhibitory activity relationship.

Indole and isatin (2,3-dioxindole) analogues were studied as inhibitors of MAO-A and B. They exhibited reversible and competitive MAO inhibition. Three dimensional structures of the compounds tested were constructed and minimized using PC-based molecular graphic software.

[Medico-biological aspects of biochemistry of amines and other nitrogen bases].

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.

New catalytic properties of monoamine oxidase immobilized in Langmuir-blodgett films with amphiphilic polyelectrolytes.

Langmuir-Blodgett (LB) films of monoamine oxidase (MAO) have been formed on the surface f a polypropylene membrane using amphiphilic polyelectrolytes. The enzyme activity of such protein-polyelectrolyte films was measured by a Clark electrodes. It was shown that in LB films thus formed the use of amphiphilc polyelectrolytes, MAO activity was higher than in polyelectrolyte-free LB films.

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.

[The action of befol and its derivatives on monoamine oxidase of different origins].

The effect on deamination of serotonine, dopamine, tiramine and 2-phenylamine of benzamide derivatives befol, moclobemide and LIS-641 was studied. Befol and moclobemide are inhibitors of serotonine deaminating activity of MAO. The different sensitivity of this activity to the effect of the benzamide derivatives in beef or rat brain and human placenta was noted.

[Selective inhibition of monoamine oxidase in bovine brain by befol and moclobemide].

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.