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Control theory of one enzyme
B N Kholodenko1, H V Westerhoff
1A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia.
Biochimica Et Biophysica Acta
|October 19, 1994
Summary
A new theory quantifies enzyme control, analyzing how individual steps affect reaction rates and enzyme states. It reveals that the slowest or largest free energy drop steps do not necessarily limit enzyme performance.
Area of Science:
- Biochemistry
- Enzyme kinetics
- Biophysical chemistry
Background:
- Metabolic control theory provides a framework for understanding cellular regulation.
- Enzyme catalysis is fundamental to biological processes, but its control mechanisms require detailed analysis.
- Existing theories may oversimplify the complex interplay of factors governing enzyme activity.
Purpose of the Study:
- To develop an analogue of metabolic control theory for single enzyme-catalyzed reactions.
- To quantify the control exerted by elemental transitions within enzyme catalytic cycles.
- To establish general theorems for understanding enzyme control mechanisms.
Main Methods:
- Application of the principle of detailed balance to quantify control.
- Derivation of cycle summation theorems for complex kinetic schemes.
- Expression of control coefficients in terms of free energy differences for simplified cases.
Main Results:
- Quantification of control on reaction rate and enzyme state probabilities.
- Demonstration of cycle summation theorems, with total control on flux, state probability, and branch flux ratios equaling 1, 0, and 0, respectively.
- Derivation of general connectivity theorems linking control to elemental step kinetics.
Conclusions:
- The developed theory provides a rigorous framework for analyzing enzyme-catalyzed reactions.
- It challenges the conventional understanding of rate-limiting steps in enzyme performance.
- The findings enable a more nuanced analysis of enzyme control mechanisms.