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B Korzeniewski

Publications and source records attributed to B Korzeniewski.

27 records · Page 2Linked to original sources
PubMed1996

Regulation of cytochrome oxidase: theoretical studies.

Using the dynamic model of oxidative phosphorylation developed previously and tested for its validity under a broad range of conditions some properties of cytochrome oxidase in the whole system considered were simulated. The regulation of this enzyme by oxygen concentration, delta p and reduction level of cytochrome c were studied. Assuming at least qualitative validity of the model, the following conclusions were drawn: (1) Regulation of cytochrome oxidase is different under the same conditions, when changes in the system (oxidative phosphorylation in isolated mitochondria) are imposed by a decrease in oxygen concentration (aerobiosis-->anaerobiosis transition) or by addition of hexokinase (state 4-->state 3 transition). In the former case, cytochrome c and delta p play a very similar role in the compensation for a decrease in the respiration rate caused by lowered oxygen concentration, while in the latter case changes in delta p activate cytochrome oxidase much stronger than changes in the reduction level of cytochrome c. (2) There is no unique thermodynamic flux-force relationship for cytochrome oxidase. This relationship depends on how the thermodynamic span of the reaction catalyzed by this enzyme is changed (aerobiosis-->anaerobiosis transition vs. state 4-->state 3 transition). (3) Under some conditions (aerobiosis-->anaerobiosis transition) the flux-force relationship can be inverse, i.e. increase in a thermodynamic force occurs simultaneously with decrease in a reaction rate.

Aerobiosis↗
PubMed1996

Simulation of oxidative phosphorylation in hepatocytes.

The dynamic mathematical model of oxidative phosphorylation proposed previously was modified, developed and further tested. The description of cytochrome oxidase kinetics was changed to involve dependence on Deltap. Simple, phenomenological descriptions of the kinetics of substrate dehydrogenation and ATP usage, able to reflect experimental data correctly, were found. The kinetic response of the oxidation subsystem (substrate dehydrogenation, respiratory chain), phosphorylation subsystem (ATP synthase, ATP/ADP carrier, phosphate carrier, ATP usage) and proton leak to the changes of Deltap in isolated hepatocytes incubated with different respiratory substrates was simulated. The simulations revealed a good agreement with the experimental results. Simple, intuitive assumptions were able, when introduced into the model, to explain differences in the properties of the oxidative phosphorylation system working with different respiratory substrates. It was proposed, therefore, that our explicit understanding of the oxidative phosphorylation system was good enough to explain many properties of this system correctly, at least in the range of physiological conditions tested.

Adenosine Diphosphate↗
PubMed1996

Theoretical studies on control of oxidative phosphorylation in muscle mitochondria at different energy demands and oxygen concentrations.

The mathematical dynamic model of oxidative phosphorylation in muscle mitochondria developed previously was used to calculate the flux control coefficients of particular steps of this process in isolated mitochondria at different amounts of hexokinase and oxygen concentrations. The pattern of control was completely different under different conditions. For normoxic concentration, the main controlling steps in state 4, state 3.5 and state 3 were proton leak, ATP usage (hexokinase) and complex III, respectively. The pattern of control in state 4 was not changed at hypoxic oxygen concentration, while in state 3.5 and state 3 much of the control was shifted from other steps to cytochrome oxidase. The implications of the theoretical results obtained for the regulation of oxidative phosphorylation in intact muscle are discussed.

Adenosine Triphosphate↗
PubMed1996

Simulation of state 4 --> state 3 transition in isolated mitochondria.

The mathematical dynamic model of oxidative phosphorylation developed previously and in the accompanying paper was modified to involve isolated mitochondria conditions; it was also used to simulate state 4 --> state 3 transition in rat liver mitochondria incubated with succinate as respiratory substrate and glucose-hexokinase as an ADP-regenerating system. Changes in the respiration rate, protonmotive force and reduction level of ubiquinone and cytochrome c as well as the internal (i) and external (e) ATP/ADP ratio between state 4 and state 3 were calculated and compared with the experimental data. Flux control coefficients with respect to oxygen consumption flux for different reactions and processes of oxidative phosphorylation were simulated for different values of the respiration rate (state 4, state 3 and intermediate states). Flux control coefficients for the oxidation, phosphorylation and proton leak subsystems with respect to the oxidation, phosphorylation and proton leak fluxes for different values of the respiration rate were also calculated. These theoretical data were compared with the experimental results obtained in the frame of metabolic control analysis and the 'top-down' approach to this analysis. A good agreement was obtained. Simulated time courses of the respiration rate, the protonmotive force (Deltap) and other parameters after addition of a small amount of ADP to mitochondria in state 4 mimicked at least semiquantitatively the experimentally measured time courses of these parameters. It was concluded, therefore, that in the present stage, the model is able to reflect different properties of the oxidative phosphorylation system in a broad range of conditions fairly well, allows deeper insight into the mechanisms responsible for control and regulation of this process, and can be used for simulation of new experiments, thus inspiring experimental verification of the theoretical predictions.

Journal Article↗
PubMed1996

What regulates respiration in mitochondria?

A (nearly) linear dependence of the respiration rate on a given parameter value was proposed as the criterion for considering this parameter to be an efficient regulator of respiration in mitochondria. A number of possible candidates was tested using the dynamic model of oxidative phosphorylation developed previously, among others ADP, the ATP/ADP ratio, external phosphorylation potential and Atkinson's adenylate energy charge. Only the external phosphorylation potential log(ATP/ADP*P(i)) was found to fulfil the above-mentioned criterion and thus it was proposed to be the parameter which 'actually' regulates oxidative phosphorylation in mitochondria.

Animals↗
PubMed1995

Proportional activation coefficients during stimulation of oxidative phosphorylation by lactate and pyruvate or by vasopressin.

A 'proportional activation' approach designed to deal with the influence of external effectors within biochemical systems is described. The proportional activation coefficient, which enables the quantitative determination of the relative stimulation of different parts of a system by a given effector, is defined. The proportional activation approach was used to calculate the relative activation of delta p-producing and delta p-consuming subsystems during stimulation of the respiration rate of cells by a variety of different effectors. Oxidative phosphorylation was stimulated by the addition of either lactate and pyruvate (10 mM and 1 mM) or vasopressin. The addition of lactate and pyruvate to suspensions of resting hepatocytes increased the respiration rate by about 50%. The delta p-consuming subsystem was stimulated about 60% as much as the delta p-producing subsystem. Quinolinic acid, commonly considered to be a specific inhibitor of gluconeogenesis, was found to block the delta p-producing oxidative subsystem as well as the delta p-consuming subsystem, indicating some nonspecific effects of this inhibitor. Addition of vasopressin to hepatocytes that were incubated in the presence of lactate and pyruvate resulted in an increase of the respiratory rate by up to 35%. The relative stimulation of the delta p-producing and delta p-consuming subsystems was essentially equal. Using the 'proportional activation approach' to analyse these and previously published data, it is shown that substrates (lactate/pyruvate and fatty acids), Ca(2+)-acting hormones (vasopressin and others) and calcium in muscles (heart muscle and skeletal muscle) activate both subsystems to a similar extent (it concerns especially Ca(2+)-dependent systems).

Animals↗
PubMed1992

Theoretical studies on the control of the oxidative phosphorylation system.

The dynamic model developed in our previous publications [1,2] was used to calculate the flux control coefficients of oxidation, phosphorylation and proton leak fluxes for isolated mitochondria and for three modes of work of intact cells (hepatocytes). The results obtained were compared with experimental data, especially those measured in the frame of the 'top-down approach' of the metabolic control theory. A good agreement for mitochondria and for intact cells was found. The control of the oxygen consumption flux is shared between the ATP utilization (main controlling factor), substrate dehydrogenation, proton leak and, in some conditions, the ATP/ADP carrier. The phosphorylation subsystem seemed to be controlled mainly by itself, while the proton leak was influenced by all three subsystems. It was also shown that the large relative change in the enzyme activity during inhibitor titration of mitochondria or cells could lead to the overestimation of some flux control coefficient values in experimental measurements. An influence of some hormones (glucagon, vasopressin, adrenaline and others) on the mitochondrial respiration was also simulated. Our results suggest that these hormones stimulate the substrate dehydrogenation as well as the phosphorylation system (ATP usage and, possibly, the ATP/ADP carrier).

Adenosine Triphosphate↗
PubMed1991

An extended dynamic model of oxidative phosphorylation.

The presented model based on an earlier one (Korzeniewski, B. and Froncisz, W. (1989) Studia Biophys. 132, 173-187) simulates concentration changes in time of chemical compounds and thermodynamic forces during respiration of cell suspension in a closed chamber. A set of differential equations solved numerically describes the utilization of oxygen up to anaerobiosis and the behaviour of the system after a sudden pulse of oxygen. Flux control coefficients for most important reactions (enzymes) of oxidative phosphorylation were calculated. A good qualitative and (when a direct comparison is possible) quantitative agreement with experimental results can be observed. The following conclusions can be drawn from the simulation: (1) Wilson's steady state model is not in contradiction with sharing of the control over the respiration between some steps and displacement of the ATP/ADP carrier from equilibrium. (2) The overshoot characteristics of the delta microH+ time-course after reoxygenation can be explained without using the lag-phase kinetics of ATP-synthetase. (3) A 'hot region' (sharp changes of many parameters) can be distinguished when the oxygen concentration approaches zero; only cytochrome oxidase is clearly sensitive on oxygen concentration in all its range. (4) Control over oxidative phosphorylation is shared mainly between inputs of the system (ATP utilization and substrate dehydrogenation) and the proton leak.

Adenine Nucleotides↗