InterJournal Genetics, 151
Status: Submitted
Manuscript Number: [151]
Submission Date: 971216
Comment on manuscript revision number 26173
Comments and recommendation for acceptance
Author(s): Anonymous

Subject(s): BG, BG.14

Category: Review Article


This is a concise and well written minireview of the current kinetic treatment of intermediate metabolism, i.e. of the rate equations governing the interconversion of the various biomolecules participating in the synthetic and catabolic processes of the intact cell, known as the metabolic network. The rate constants of individual conversions, catalyzed by a single enzyme, as well as the flow through coupled enzymatic pathways are treated. Special emphasize is given to the nature of steps controlling metabolite flows. The author emphasizes, that the widely held concept of a single or few enzymatic steps as rate determining may be too simplistic, and control coefficients for all steps should be consulted. I am not so sure that this is necessarily the case - examples for pathways where a single enzymatic step is rather limiting are the pathway to cholesterol biosynthesis governed by the activity of HMG-CoA reductase or the pentose pathway which is governed by glucose -6-phosphate dehyrogenase. A major drawback of the present paper is that very few, if any, concrete examples are brought and documented. The reader is however referred to earlier publications of the author where examples are discussed. A further problem is that the synthesis and degradation of enzymes (induction and repression) are the major way to regulate flow of metabolites, especially in bacteria (see Yagil, G. in: "Biological kinetics", Lee A. Segel, Ed., Cambridge university press, 1990, Ch. 6.). Enzyme modification by modification (e.g. phosphorylation) is a third major regulatory mode. These two modes are barely mentioned, only towards the end of the paper. The question arises as to what extent the metabolic pathways should really be considered a complex system. There are certainly many participating components, and numerous factors influence the rate of almost any enzymatic step. a complete solution of all equations is certainly complicated. However, in spite of the fact that many of the elementary rate equations are nonlinear (Any bimolecular chemical reaction is nonlinear), the in vivo behavior has seldom been found to deviate significantly from quite simple smooth behavior. The tools of nonlinear dynamics have hitherto not been found to be required, and most measured flow can be conventionally, deterministically treated. The few deviating examples have been described in A. Goldbetter's presentation. This raises again the question when does a system belong to the category of "complex systems" - Is it when it has many components and parameters? Or when the components and parameters are not known? or not understood? In summary, the publication of this article minireview can be recommended, mainly for the benefit of quantitatively minded non-biochemists, who might want a concise, clear description of how intercellular chemical dynamics are being approached and treated.

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