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Getting to the inside of cells using metabolic control analysis
H V Westerhoff1, J H Hofmeyr, B N Kholodenko
1E.C. Slater Institute, Biocentrum of the University of Amsterdam, The Netherlands.
Biophysical Chemistry
|June 1, 1994
Summary
Metabolic control analysis now allows deducing enzyme kinetics and pathway structure from system control properties. This method reveals in situ enzyme behavior, clarifying differences from isolated enzyme kinetics.
Area of Science:
- Biochemistry
- Systems Biology
- Metabolic Engineering
Background:
- Metabolic control analysis (MCA) links system-level control properties to enzyme kinetics.
- Current MCA methods primarily focus on relating system control to enzyme elasticity coefficients.
Purpose of the Study:
- To elaborate MCA for relating system control properties to enzyme elasticity coefficients.
- To develop a reverse method for deducing pathway structure and enzyme kinetics from system control properties.
Main Methods:
- Elaboration of MCA for the general case, founded in standard metabolic control theory.
- Development of a reverse method using matrix inversion to link control coefficients with elasticity coefficients and pathway structure.
Main Results:
- A method is presented where a matrix of elasticity coefficients and pathway information is the inverse of a matrix of flux and concentration control coefficients.
- This enables the deduction of in situ pathway structure and enzyme kinetic properties from measurable system control properties.
Conclusions:
- The developed method allows for the determination of enzyme kinetic properties under cellular conditions.
- This approach addresses the long-standing question of whether isolated enzyme kinetics reflect in vivo behavior.
