Naslov
Global sensitivity analysis of tryptophan metabolism model kinetic parameters

Autori
Karatović, Anja ; Remenar, Sandra ; Herout, Brigita ; Jurina, Tamara ; Valinger, Davor ; Benković, Maja ; Gajdoš Kljusurić, Jasenka ; Jurinjak Tušek, Ana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts XIII Meeting of Young Chemical Engineers / Dejanović, Igor ; Vrsaljko, Domagoj ; Žižek, Krunoslav - Zagreb : Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2020, 71-71

ISBN
978-953-6894-71-0

Skup
XIII. susret mladih kemijskih inženjera (SMLKI 2020)

Mjesto i datum
Zagreb, Hrvatska, 20.02.2020. - 21.02.2020

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
tryptophan metabolism ; kinetic parameters ; global sensitivity analysis

Sažetak
The biggest challenge when working with mathematical models describing biological processes is to choose the appropriate values of the kinetic parameters. This applies especially to the models of the metabolically processes. Parameter values are obtained from various sources and under specific experimental conditions and constitute sources of uncertainties. Useful tool for dealing with model parameter uncertainties is sensitivity analysis. Sensitivity analysis is the study how uncertainty in the model output can be apportioned to different sources of uncertainty in the model input factor, for example model parameters. In this work global sensitivity analysis method (Fourier Amplitude Sensitivity Test, FAST) was applied for analysis of the kinetic parameters of the tryptophan metabolism model. The aim of this study was to determinate the first order sensitivities of model metabolites at three time points in order to identify the possible shift in metabolism control. Model of tryptophan metabolism proposed by Rios-Avila et al., 2013 includes mammalian data on enzyme kinetics and tryptophan transport form intestinal lumen to liver, muscle and brain. Regulatory mechanism and inhibitions of relevant enzymes were included. The analysed model is expressed in the form of 16 ordinary differential equations and includes 44 kinetic parameters. Using FAST method, the system analysis is based on evaluation of the first moments form the multidimensional joint probability distribution. Effect of each individual process variable on each of the system outputs is evaluated by ratio of the ensemble variance of the conditional expected value relative to the total ensemble dispersion. Results showed that the most important parameters for the tryptophan state concentration were (1) KmPRO-saturation constant in protein synthesise reaction, (2) vmaxTRPGS-maximum reaction rate for the reaction of tryptophan transport from gut to portal circulation and (3) k14- reaction rate of the reaction of tryptophan transport from muscles to peripheral circulation. Results also show the slight increase of the sensitivity coefficients of the listed parameters over the time.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija

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