PhD Scientific Days 2018

Oral presentations: Molecular medicine

Modeling the citric acid cycle, malate-aspartate and citrate-pyruvate shuttles

Előadó neve

Sváb, Gergely

Előadó munkahelye

Department of Medical Biochemistry

Előadó telefonszáma

+36306538006

Előadó e-mail címe

gsvab92@gmail.com

Az előadás címe

Modeling the citric acid cycle, malate-aspartate and citrate-pyruvate shuttles

Szerző(k) neve és munkahelye

Gergely Sváb, Gábor Szederkényi, Gergő Horváth, László Tretter
1 Department of Medical Biochemistry, Semmelweis Unversity
2 Faculty of Information Technology and Bionics, Pázmány Péter Catholic University
3 Department of Medical Biochemistry, Semmelweis Unversity
4 Department of Medical Biochemistry, Semmelweis Unversity

Bemutatás módja

Szóbeli

Szekció

Oral presentations: Molecular medicine

Language of the presentation

Hungarian

Témacsoport

other

Összefoglaló szövege

Introduction: In the Neurobiochemistry working group, we have taken enzyme kinetic measurements of several mitochondrial enzymes. We have determined oxygen consumption and analyzed interactions between enzymes and various respiratory substrates, but further analysis of the processes is important.

Aims: A suitable qualitative model is constructed which describes the temporal changes in the quantities of citric acid cycle's (CAC) molecules. The modeling goal is to at least qualitatively describe the increased/decreased operation of the catalyzing enzymes as well as the modified operation of the intermediate molecules. We would like to predict whether mitochondria have the ability to adapt to this new metabolic state by activating/inhibiting metabolic pathways.

Method: We modeled the reactions of CAC, malate-aspartate and citrate-pyruvate shuttles. Initially, we constructed 3 individual modules for each process, and later we combined them. The overall model is given in the form of kinetic ordinary differential equations assuming Michaelis-Menten kinetics with 39 state variables, which was implemented in MATLAB environment. The initial values of the state variables can be provided by the user, depending on the simulated metabolic status.

Results: A dynamical model was constructed and evaluated for describing the quantities in the CAC and its two transport systems. Simulation results are discussed from a biological point of view. Initially, the sub-models of the three subsystems were developed and tested, later these modules were integrated into a unified dynamical model. It is theoretically possible to study the dynamical interplay between all described species.

Conclusion: We introduced a model for describing the dynamics of key quantities in mitochondrial metabolism. Simulations show that the obtained results are qualitatively correct for our expectations. Additional laboratory measurements are in progress to determine kinetic parameters which we have incomplete knowledge about. An important planned application of the model is the dynamical description of pathological processes.

Data of the presenter

Doctoral School: János Szentágothai Doctoral School of Neurosciences
Program: Functional Neurosciences
Supervisor: László Tretter
E-mail address: gsvab92@gmail.com

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2905

Authors (legacy)

Gergely Sváb, Gábor Szederkényi, Gergő Horváth, László Tretter
1 Department of Medical Biochemistry, Semmelweis Unversity
2 Faculty of Information Technology and Bionics, Pázmány Péter Catholic University
3 Department of Medical Biochemistry, Semmelweis Unversity
4 Department of Medical Biochemistry, Semmelweis Unversity