Optimizing enzymatic catalysts for rapid turnover of substrates with low enzyme sequestration

DOI10.1007/S00422-020-00846-6zbMATH Open1460.92074DBLPjournals/bc/DeshpandeO20arXiv1905.00555OpenAlexW3092060013WikidataQ100522742 ScholiaQ100522742MaRDI QIDQ2659627FDOQ2659627

Authors: Abhishek Deshpande, Thomas E. Ouldridge 

Publication date: 26 March 2021

Published in: Biological Cybernetics (Search for Journal in Brave)

Abstract: We analyse the mechanism of enzyme-substrate catalysis from the perspective of minimizing the load on the enzymes through sequestration, whilst maintaining at least a minimum reaction flux. In particular, we ask: which binding free energies of the enzyme-substrate and enzyme-product reaction intermediates minimize the fraction of enzymes sequestered in complexes, while sustaining at a certain minimal flux? Under reasonable biophysical assumptions, we find that the optimal design will saturate the bound on the minimal flux, and reflects a basic trade-off in catalytic operation. If both binding free energies are too high, there is low sequestration, but the effective progress of the reaction is hampered. If both binding free energies are too low, there is high sequestration, and the reaction flux may also be suppressed in extreme cases. The optimal binding free energies are therefore neither too high nor too low, but in fact moderate. Moreover, the optimal difference in substrate and product binding free energies, which contributes to the thermodynamic driving force of the reaction, is in general strongly constrained by the intrinsic free-energy difference between products and reactants. Both the strategies of using a negative binding free-energy difference to drive the catalyst-bound reaction forward, and of using a positive binding free-energy difference to enhance detachment of the product, are limited in their efficacy.

Full work available at URL: https://arxiv.org/abs/1905.00555

Recommendations

• Single-substrate enzyme kinetics: the quasi-steady-state approximation and beyond
• Mathematical modeling to optimize the product in enzyme kinetics
• An evolutionary approach to enzyme kinetics: Optimization of ordered mechanisms
• Sensitivity analysis of a linear and unbranched chemical process with \(n\) steps
• A theoretical approach to the evolution and structural design of enzymatic networks; linear enzymatic chains, branched pathways and glycolysis of erythrocytes

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40)

Cites Work

• Markov Chains
• Landauer in the age of synthetic biology: energy consumption and information processing in biochemical networks
• Chemical biophysics. Quantitative analysis of cellular systems.
• Thermodynamic constraints for biochemical networks
• Biomolecular feedback systems
• Retroactivity Attenuation in Bio-Molecular Systems Based on Timescale Separation
• Implementing Non-Equilibrium Networks with Active Circuits of Duplex Catalysts.

This page was built for publication: Optimizing enzymatic catalysts for rapid turnover of substrates with low enzyme sequestration

Report a bug (only for logged in users!)Click here to report a bug for this page (MaRDI item Q2659627)