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Your search keyword '"Šterk, Marko"' showing total 3 results
Start Over Author "Šterk, Marko" Publisher elsevier b.v.
3 results on '"Šterk, Marko"'

2. Flexibility of enzymatic transitions as a hallmark of optimized enzyme steady-state kinetics and thermodynamics.

Author

Šterk, Marko, Markovič, Rene, Marhl, Marko, Fajmut, Aleš, and Dobovišek, Andrej

Subjects
*ENZYME kinetics, *TRIOSE-phosphate isomerase, *THERMODYNAMICS, *ENTROPY (Information theory), *MAGNITUDE (Mathematics), *MOLECULAR conformation, *BIOCATALYSIS, *ISOMERASES
Abstract

[Display omitted] • Optimization of enzyme kinetic flexibility is performed for the four-state enzyme reaction. • Maximal kinetic flexibility results in the global optimal enzyme state. • Kinetic flexibility is linked to entropy production and Shannon information entropy. • Maximal kinetic flexibility results in maxima of entropy production and of Shannon information entropy. • Kinetic flexibility of the enzymatic structure plays a crucial role in the natural enzyme design. We investigate the relations between the enzyme kinetic flexibility, the rate of entropy production, and the Shannon information entropy in a steady-state enzyme reaction. All these quantities are maximized with respect to enzyme rate constants. We show that the steady-state, which is characterized by the most flexible enzymatic transitions between the enzyme conformational states, coincides with the global maxima of the Shannon information entropy and the rate of entropy production. This steady-state of an enzyme is referred to as globally optimal. This theoretical approach is then used for the analysis of the kinetic and the thermodynamic performance of the enzyme triose-phosphate isomerase. The analysis reveals that there exist well-defined maxima of the kinetic flexibility, the rate of entropy production, and the Shannon information entropy with respect to any arbitrarily chosen rate constant of the enzyme and that these maxima, calculated from the measured kinetic rate constants for the triose-phosphate isomerase are lower, however of the same order of magnitude, as the maxima of the globally optimal state of the enzyme. This suggests that the triose-phosphate isomerase could be a well, but not fully evolved enzyme, as it was previously claimed. Herein presented theoretical investigations also provide clear evidence that the flexibility of enzymatic transitions between the enzyme conformational states is a requirement for the maximal Shannon information entropy and the maximal rate of entropy production. [ABSTRACT FROM AUTHOR]

Published
2021
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3. Assessing the origin and velocity of Ca2+ waves in three-dimensional tissue: Insights from a mathematical model and confocal imaging in mouse pancreas tissue slices.

Author

Šterk, Marko, Dolenšek, Jurij, Bombek, Lidija Križančić, Markovič, Rene, Zakelšek, Darko, Perc, Matjaž, Pohorec, Viljem, Stožer, Andraž, and Gosak, Marko

Subjects
*PANCREATIC beta cells, *ISLANDS of Langerhans, *MATHEMATICAL models, *VELOCITY, *BETA rhythm, *SPHERICAL waves
Abstract

• Intercellular Ca2+ waves coordinate the function of multicellular systems. • Determining the origin and velocity of Ca2+ waves in 3D tissue is challenging. • We combined Ca2+ imaging with models to study Ca2+ waves in beta cell networks. • The origin and velocity of Ca2+ waves in pancreatic islets are revealed. • Our theoretical and numerical results are of particular value to experimentalists. Many tissues are gap-junction-coupled syncytia that support cell-to-cell communication via propagating calcium waves. This also holds true for pancreatic islets of Langerhans, where several thousand beta cells work in synchrony to ensure proper insulin secretion. Two emerging functional parameters of islet function are the location of wave initiator regions and the velocity of spreading calcium waves. High-frequency confocal laser-scanning imaging in tissue slices is one of the best available methods to determine these markers, but it is limited to two-dimensional cross-sections of an otherwise three-dimensional islet. Here we show how mathematical modeling can significantly improve this limitation. Firstly, we analytically determine the shape of velocity profiles of spherical excitation waves in the focal plane of a homogeneous three-dimensional space. Secondly, we introduce a mathematical model consisting of coupled excitable cells that considers cellular heterogeneities to approach more realistic conditions by means of numerical simulations. We demonstrate the effectiveness of our approach on experimentally recorded waves from an islet that was stimulated with 9 mM glucose. Furthermore, we show that calcium waves were primarily triggered by a specific region located 30 µm bellow the focal plane at the periphery of the islet. Additionally, we show that the velocity of the calcium wave was around 80 µm/s. We discuss the importance of our approach for the correct determination of the origin and velocity of calcium waves from experimental data, as well as the pitfalls that are due to improper procedural simplifications. [ABSTRACT FROM AUTHOR]

Published
2021
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