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Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

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'Slave' metabolites and enzymes. A rapid way of delineating metabolic control.

B Teusink¹, H V Westerhoff

¹E. C. Slater Institute, BioCentrum Amsterdam, University of Amsterdam, the Netherlands.

European Journal of Biochemistry

|March 23, 2000

Summary

Metabolic control is often distributed, but some enzymes lack it entirely. This study reveals "slave enzymes" controlled by single metabolites, impacting metabolic signal transduction and potentially misinforming models.

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Area of Science:

Biochemistry
Systems Biology
Metabolic Engineering

Background:

Metabolic control is typically distributed across multiple enzymes.
However, some enzymes exhibit little to no control over metabolic variables.

Purpose of the Study:

To identify the origins of enzymes lacking metabolic control.
To introduce the concept of "slave enzymes" and "slave metabolites".

Main Methods:

Theoretical analysis of metabolic control.
Examination of the glycolytic pathway in yeast.

Main Results:

Identified "slave enzymes" whose catalytic rates are affected by only one metabolite.
Demonstrated that these enzymes cannot control any variable other than their specific metabolite's concentration.
Discussed implications for downstream enzyme control and signal transduction.

Conclusions:

The existence of slave enzymes can lead to a lack of control in metabolic pathways.
This phenomenon may be crucial for metabolic signal transduction.
Metabolic models must account for slave enzymes to avoid inaccurate control calculations.