Influence of ethanol administration on the activity and compartmentation of rat liver monoamine oxidases.

Single-dose ethanol administration to rats caused inhibition of liver mitochondrial monoamine oxidases (MAO) A and B, and an increase in susceptibility of MAO A (but not MAO B) to limited proteolysis. Chronic ethanol feeding resulted in a less distinct alteration in catalytic activity and susceptibility to proteolysis of mitochondrial MAO, but increased the amount of soluble MAO. The sensitivity of membrane-bound MAO to inhibitors (imipramine and chlorpromazine), action of which depends on their lipophilicity and/or hydrophobicity, remained unchanged, compared with controls.

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.

[Features of the biochemical action of paraquat on oxidative deamination of biogenic amines and other nitrogen compounds].

Intoxication of rats with the herbicide paraquat (1,1-dimethyl-4,4-bipyridilium dichloride) was accompanied by accumulation in lungs, brain, heart, liver or kidney of malonic dialdehyde (MDA) (the compounds reacting with 2-thiobarbituric acid), indicating that the intoxication stimulated lipid peroxidation (LPO) in biomembranes. Treatment of the intoxicated rats with the antioxidant diludin (2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine) or with the nucleophilic reagents sodium ascorbate or thiosulphate normalized the content of MDA in lungs, brain, heart, liver or kidney demonstrating the reversibility of the LPO stimulation caused by paraquat. On incubation of mitochondrial fractions of homogenates of lungs, brain, heart, liver or kidney of the intoxicated rats (as compared with the corresponding fractions from the intact animals) a decrease was noted in deamination of the substrates of monoamine oxidases serotonin, tryptamine, benzylamine, tyramine; at the same time, deamination of glucosamine and gamma-aminobutyric acid was increased and deamination of putrescine and L-lysine appeared.

Endogenous stimulation of lipid peroxidation in brain increases proteolytic inactivation of mitochondrial monoamine oxidases.

Stimulation of lipid peroxidation in vivo (in experimental epilepsy and closed cranio-cerebral injury, as models for endogenous stimulation of lipid peroxidation) affects catalytic activity, substrate specificity of mitochondrial monoamine oxidases and increases their susceptibility to trypsinolysis. It is suggested that increased susceptibility to trypsinolysis reflects an appearance of new hydrophilic site(s) in monoamine oxidase molecules which may be responsible for an involvement of the modified enzymes in the deamination of other important nitrogenous compounds (such as gamma-aminobutyric acid) with subsequent impairment of a ratio between inhibition and excitation processes in the brain.