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Biomedical subjects

A M Zhabotinskiĭ

Publications and source records attributed to A M Zhabotinskiĭ.

At least 19 recordsLinked to original sources

[The resonance nature of the dependence of epithelial lesions of the small intestine in mice on the interval between injections of an S-phase-specific agent--hydroxyurea].

The dependence of the injury of murine small intestinal epithelium on the interval between multiple regular injections of hydroxyurea (HU) was investigated. Mice were injected 8 times with HU (5 mg per injection) in different experimental groups of animals, and the interval between injections varied from 6 to 19 hours. With the intervals between the injections close to 8 or 16.5 hours the resonance decrease of the injury was observed whereas the intervals of 6, 12 and 19 hours corresponded to maximum injury.

Animals↗

[Relation between the toxic killing of mouse small intestine enterocytes and the interval between the administration of the S-specific agent hydroxyurea].

The dependence of small intestinal lesions on the interval between repeated regular injections of hydroxyurea was studied. The doses of 1 g/kg and 0.2 g/kg were used. To activate the enterocyte proliferation the mice were pre-irradiated at 2 Gy. 3-4 hours after the last hydroxyurea injection the two distinct minimum points of epithelial lesions were observed at interinjection intervals of 9 and 16.5 hours. The result was dose-independent.

Animals↗

[Metabolic changes leading to oxidative lysis of erythrocytes maintained in a normal state in vitro].

It was shown that in vitro oxidative hemolysis of human erythrocytes occurs as a result of a great increase in membrane permeability to cations leading to osmotic damage of the cells. Infusion at a steady rate with a solution of tert-butylhydroperoxide in an erythrocyte suspension resulted in a rapid fall of the reduced glutathione level down to 0, when the rate of infusion exceeded the maximal rate of pentose phosphate pathway. Under these conditions the potassium ions liberation from the erythrocytes began with the drop of the reduced glutathione level down to zero, and the hemoglobin liberation - at the moment when more than 60% of potassium ions were liberated from the erythrocytes. The kinetics of potassium ion liberation remained unchanged in anisotonic media, but hemoglobin liberation from the erythrocytes greatly increased in hypotonic media as compared with isotonic ones. The kinetics of K+ and hemoglobin liberation were correlated only with lipid peroxidation but not with the oxidation of protein SH-groups.

Cell Membrane Permeability↗

[Resonance nature of the relation of mouse survival to the interval between administrations of the S-specific agent--hydroxyurea].

The dependence of murine survival on the intervals between periodic hydroxyurea (HU) injections was studied. The single dose of HU comprised 250 mg per kg. Intervals between injections varied from 5 to 19 hours while their number changed from 6 to 9 in different experiments. A resonant increase in the survival was observed under HU administered every 8-9 or 16 1/2 hours.

Animals↗

[The 2,3-diphosphoglycerate shunt and stabilization of the ATP level in mammalian erythrocytes].

The mechanisms of regulation of energy metabolism in erythrocytes of various mammalian species were investigated. In native erythrocytes of man, sheep, cow, dog and mouse the dependencies of the rates of glucose uptake on ATP concentration (i.e., regulatory parameters of glycolysis) were measured. These parameters plotted in normalized coordinates are not species-specific (invariant). The dependence of the rate of ATP-consuming processes on ATP concentration has been studied for the first time in intact mammalian erythrocytes. This dependence was found to be linear only in the species, in whose erythrocytes the activity of 2,3-diphosphoglycerate shunt is practically zero. In all species under study, the stabilization of ATP level is provided for mainly by the hexokinase-phosphofructokinase system. A comparison of regulatory mechanisms of energy metabolism in mammalian (sheep, cow) erythrocytes, in which the 2,3-diphosphoglycerate shunt is absent, with human and animal erythrocytes, in which this pathway is active, points to the important role of the 2,3-diphosphoglycerate shunt in regulation of energy conversion in erythrocytes. This shunt operates as an additional stabilizer protecting the cell from extremal influences.

2,3-Diphosphoglycerate↗

[Permeability of human erythrocytes to asparagine].

Asparagine is able to penetrate into human erythrocytes from the external medium. The dependence of the asparagine transport rate on its concentration can be described by the Michaelis-Menten equation with parameters: Km = 2.50 mM, V = 0.24 mmol/l cells per hour. Loading of erythrocytes with asparaginase does not influence their permeability to asparagine. Aspartate is accumulated inside these erythrocytes during incubation with asparagine, thus reflecting rapid transformation of penetrating asparagine by entrapped asparaginase.

Asparaginase↗

[Steady-state dependence of the methemoglobin reduction rate on its concentration in intact human erythrocytes].

The rate of methemoglobin reduction by the methemoglobin reductase system of intact human erythrocytes was measured as a rate of pyruvate formation in a quasi-steady state. Various methemoglobin concentrations (up to 100%) were generated by sodium nitrite additions. The steady state methemoglobin levels were maintained by infusion of a nitrite solution at a rate of 2.8 mmol/h/l cells. The rate of pyruvate formation was proportional to the steady state methemoglobin concentration in the range from the physiological value to 100%, the maximal value being as high as 500 mumol/h/l cells. It was found that the rate of CO2 output by the erythrocytes markedly increased in the presence of 8 mM sodium nitrite, reaching up to about 40% of the possible maximal value.

Carbon Dioxide↗

[Effect of glycolysis on the metabolism of adenylates in human erythrocytes].

The ATP content in human erythrocytes depleted without glucose falls down to half of the initial value within 2-3 hours and reaches practically zero within more than 10 hours. The ADP content increases 2-3-fold during the 1st hour after depletion and then slowly decreases. The AMP content increases 10-fold during several hours, but the rate of this process constantly decreases. The adenylate pool decreases at a constant rate ranging from 0.13 to 0.25 mmol/l cell. h; this is accompanied by accumulation of IMP. Addition of glucose to depleted erythrocytes results in partial recovery of the ATP level within 1-2 hours. The sooner glucose addition after the depletion, the greater the recovery. Simultaneously the ADP and AMP levels drastically decrease to new constant values. The decline of the adenylate pool ceases and the rate of IMP accumulation increases. Normally, the [ATP]/adenylate pool ratio lies within the small interval 0.85-0.94 irrespective of significant individual differences in the absolute values of [ATP]. This ratio is decreased during depletion and restored to the initial value after glucose addition. The mass-action ratio of the adenylate kinase reaction changes greatly during depletion and restoration of erythrocyte ATP.

2,3-Diphosphoglycerate↗

[Relation of the survival of mouse hematopoietic stem cells to the interval between periodic injections of hydroxyurea].

The dependence was studied between the survival of proliferating hemopoietic stem cells (CFUs) on the interval between regular multiple injections of hydroxyurea (HU). Before HU injection mice were irradiated in a dose of 200 rad to trigger the proliferation of CFUs. The dependence obtained is resonance in character, with a maximum being attained during injections made with a 12-hour interval. Comparison with the mathematical model indicates that interval corresponding with the maximal survival should correlate with the mean time of the generation of proliferating CFUs.

Animals↗

[Regulatory characteristics of glycolysis in erythrocytes of sheep].

The regulatory properties of glycolysis in sheep erythrocytes (i. e. dependence of the rate of glucose uptake on ATP concentration) were investigated. A decrease of ATP concentration in the erythrocytes by arsenate causes a sharp rise in the rate of glycolysis, the maximal rate being reached at ATP concentration of about 70% of the original one. Further decrease of ATP lowers the rate of glycolysis; no steady-state rates of energy metabolism are observed within this concentration range. The parameters of glycolysis measured in erythrocytes of various species coincide when the rates of glycolysis are normalized in terms of its maximal value and that of ATP -- in terms of its value at which the maximal rate is reached. The identities of regulatory properties of glycolysis take place even upon two-fold differences in the absolute values of rates and concentrations.

Adenosine Triphosphate↗

[Dependence of the rate of the pentose cycle reactions on the degree of glutathione reduction in erythrocytes].

The stationary dependence of the rate of pentose cycle in erythrocytes measured by CO2 production on the degree of glutathione reduction typical for the pentose cycle was established. The steady-state rate of oxidation from the physiological to maximal values was generated by the addition of tretbutylhydroperoxide, a substrate of the glutathione peroxidase reaction, to erythrocyte suspension at a constant rate. The steady-state rate of CO2 production was correlated with the rates of oxidant addition throughout the experiment. The parameters of the pentose cycle reactions under conditions when the maximal rate of the pentose cycle and glutathione pool (GSH+2 GSSG) are taken for 100%, coincided for all donors tested. The increase in the rate of pentose cycle from 0 to 60% of the maximal one had practically no effect on the concentration of GSH, which was as high as 90% of the overall glutathione pool, thus indicating a high stabilization degree of GSH (stabilization coefficient was about 15). A further increase of the rate up to maximal values resulted in a rapid fall of the GSH level down to 0. The data obtained support the previously described mathematical model for regulation of glutathione metabolism. The GSSG liberation from the erythrocytes was shown to be directly proportional to the stationary intracellular concentration of GSSG; the transport rate constant varied in different donors from 0.15 up to 0.6(-1). The increase of oxidation rates up to maximal values, when GSSG concentration was approximated to the glutathione pool leads to a reversible decrease of GSSG concentration, which destroys the steady-state equilibrium of the pentose cycle.

Carbon Dioxide↗

[Mathematical model for energy metabolism in erythrocytes. Independence of scaled glycolytic characteristics of individual features of the donors].

A mathematical model for energy metabolism of erythrocytes includes the first three enzymes of the Embden-Meyerhof pathway as well as total ATPase. It was assumed that the ATPase is strongly inhibited by AMP. The model was used to calculate the dependence of the rate of ATP production and glucose consumption on ATP concentration, i. e. characteristics of glycolysis. The scaled characteristics were plotted in relative units, the normal physiological values of the rates of glucose consumption and ATP concentration being taken for 100%. It was shown that the scaled characteristics show a coincidence, the precision being 20%, when the values of the enzyme activities and other parameters of the model vary within 100%. This agrees with the data, where the scaled characteristics of glycolysis in different donors (in all donors) coincide with experimental precision, while the values of the rates and concentrations with respect to the absolute value varied within 100%.

Adenosine Triphosphatases↗

[Interrelationship between the rate of ATP-consuming processes and ATP concentration in intact erythrocytes].

The behaviour of ATP concentrations in intact erythrocytes upon glucose addition to the erythrocyte suspension at a constant rate was studied. At different rates of glucose addition lower than the rate of glucose consumption at normalcy, the corresponding ATP concentrations are established, which are dependent on the rate of glucose influx. The 20% decrease of ATP concentration from the physiological value is observed at a 2-fold decrease of the flux. The results obtained made it possible to establish the dependence of the total rate of ATP consumption on ATP concentration in intact erythrocytes. This dependence is non-linear and shows a dramatic rise in the proximity of the physiological point.

Adenosine Triphosphate↗

[Quantitative model of human erythrocyte glycolysis. I. Relationship between the stationary rate of glycolysis and the ATP concentration].

A mathematical model is presented of the Embden--Meyerhof pathway in the human red blood cell. The rate of the system stationary flux is determined by the first part of the chain including three enzymatic reactions. The function has been calculated which describes the dependence of the stationary rate of glucose consumption and ATP production on the concentration of ATP. The curve has a bell shape with the physiological normal point situated in the descending segment. The descending segment is a result of the inhibition of the phosphofructokinase by ATP and the strong inhibition of the hexokinase by glucose-6-phosphate.

Adenosine Triphosphate↗

[Quantitative model of human erythrocyte glycolysis. Region of cell viability determined by ATP concentration].

The boundaries of the cell vitality domain in the enzyme activity space are calculated on the basis of a mathematical model of erythrocyte glycolysis. The boundaries are determined by key metabolite concentrations. The results obtained are compared with experimental data related to erythrocytic enzymopathies. It is shown that theoretical boundary enzyme activities coincide with the activities of hexokinase and in some cases phosphofruktokinase in enzyme deficient erythrocytes.

Adenosine Triphosphatases↗

[Photoinduced reduction of ferriperoxidase. I. Reaction with reduced nicotinamide-adenine dinucleotide].

Photoinduced reduction of peroxidase with reduced NAD is revealed.; its kinetics is studied. The kinetic scheme of this process is suggested and calculated. It is shown that metastable excited state appears after NAD-N irradiation. This state participated in the reaction with ferriperosidase. It is also shown that the NAD radical which appears in the course of this reaction reduces the peroxidase; the rate constant of this process is (5 +/- 0,5) -10(4) M-1 sec-1.

NAD↗

[Quantitative model of human erythrocyte glycolysis. Relationship between erythrocyte energy metabolism and Na+, K+-ATPase activity].

The influence of the changes of the transport Na+, K+-ATPase activity on the human red blood cell (RBC) glycolysis was studied. Two different types of energetic regulation were found out under the strophanthin inhibition. A decrease of ATP comsumption results in a drop of glucose consumption and lactate production in the first type regulation of RBC. In the second type regulation of RBC the glucose consumption does not change after ATPase inhibition and the excess metabolic flux is directed through the hexosemonophosphate shunt. In both cases the resulting decrease of ATP production leads to the ATP level stabilization. An increase of potassium ions concentration in the external medium does not influence the RBC glycolysis. The valinomycin added increases the glucose consumption and the lactate production. The cell volume decreases under the effect of valinomycin.

Erythrocytes↗