Is the catalytic activity of triosephosphate isomerase fully optimized? An investigation based on maximization of entropy production
| Autor: | Željana Bonačić Lošić, Tomislav Donđivić, Davor Juretić |
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| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular 0301 basic medicine Specificity constant Original Paper 030102 biochemistry & molecular biology Entropy production Chemistry Entropy Enzyme kinetic scheme Triosephosphate isomerase Maximum entropy production Kinetic constants Biophysics Thermodynamics Cell Biology Maximization Atomic and Molecular Physics and Optics Reaction rate Kinetics 03 medical and health sciences 030104 developmental biology Product (mathematics) Biocatalysis Enzyme kinetics Molecular Biology Flux (metabolism) Triose-Phosphate Isomerase |
| Zdroj: | Journal of Biological Physics. 43:69-86 |
| ISSN: | 1573-0689 0092-0606 |
| DOI: | 10.1007/s10867-016-9434-3 |
| Popis: | Triosephosphate isomerase (TIM) is often described as a fully evolved housekeeping enzyme with near-maximal possible reaction rate. The assumption that an enzyme is perfectly evolved has not been easy to confirm or refute. In this paper, we use maximization of entropy production within known constraints to examine this assumption by calculating steady-state cyclic flux, corresponding entropy production, and catalytic activity in a reversible four-state scheme of TIM functional states. The maximal entropy production (MaxEP) requirement for any of the first three transitions between TIM functional states leads to decreased total entropy production. Only the MaxEP requirement for the product (R-glyceraldehyde-3-phosphate) release step led to a 30% increase in enzyme activity, specificity constant kcat/KM, and overall entropy production. The product release step, due to the TIM molecular machine working in the physiological direction of glycolysis, has not been identified before as the rate-limiting step by using irreversible thermodynamics. Together with structural studies, our results open the possibility for finding amino acid substitutions leading to an increased frequency of loop six opening and product release. |
| Databáze: | OpenAIRE |
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