Simulation of the glycolytic metabolites concentration profile in mammalian resting skeletal muscles

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Abstract

For the first time, a mathematical model of glycolysis in mammalian skeletal muscles is presented, in which stationary concentrations of glycolysis metabolites are in good agreement with experimental data obtained in resting muscles. The correspondence between the model and experimental values of metabolite concentrations was achieved due to enhancing the inhibitory effect of ATP on pyruvate kinase and significantly reducing the ratio of [NAD]/[NADH] concentrations in the cytoplasm of skeletal muscles. At the same time, in order for glycolysis to provide the rate of ATP production necessary for activation of muscle load, an activation of muscle pyruvate kinase by fructose-1,6-diphosphate was included in the model.

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About the authors

M. V. Martinov

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences

Email: victor_vitvitsky@yahoo.com
Russian Federation, Moscow, 109029

F. I. Ataullakhanov

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences; Moscow Institute of Physics and Technology

Email: victor_vitvitsky@yahoo.com
Russian Federation, Moscow, 109029; Dolgoprudny, Moscow oblast, 141701

V. M. Vitvitsky

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences

Author for correspondence.
Email: victor_vitvitsky@yahoo.com
Russian Federation, Moscow, 109029

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2. Fig. 1. Biochemical reactions included in the model. The following designations for enzymes and metabolites were used in the work: AK – adenylate kinase, ALD – aldolase, ATPase – the sum of ATP-consuming processes, excluding hexokinase and phosphofructokinase reactions, ENO – enolase, GAPDH – glyceraldehyde phosphate dehydrogenase, GPI – glucose phosphate isomerase, HK – hexokinase, PK – pyruvate kinase, PFK – phosphofructokinase, PGK – phosphoglycerate kinase, PGM – phosphoglycerate mutase, TPI – triosephosphate isomerase, 1,3-DPG – 1,3-diphosphoglycerate, 2-PG – 2-phosphoglycerate, 3-PG – 3-phosphoglycerate, DAP – dihydroxyacetone phosphate, F6P – fructose-6-phosphate, FDP – fructose-1,6-diphosphate, G6P – glucose-6-phosphate, GAP – glyceraldehyde phosphate, GLU – glucose, PEP – phosphoenolpyruvate. The dotted arrow shows the production of G6P from glycogen at a rate of VGLY.

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3. Fig. 2. Effect of pyruvate kinase activation by fructose-1,6-diphosphate on the rate of ATP production in the model during stimulation of muscle work. a, b – Relationship between the rate of G6P production from glycogen (VGLY) and the steady-state rate of ATP production during stimulation of muscle work in the model with PK independent of FDP (a) and with PK activated by FDP (b). c, d – Dependence of steady-state concentrations of glycolytic metabolites on the rate of ATP production in the model with PK independent of FDP (c) and with PK activated by FDP (d). Stimulation of muscle work is considered as an increase in the rate of ATP consumption. The graphs show steady-state values ​​of rates and concentrations. Therefore, in all cases, the rates of ATP production and consumption are equal.

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