Regulatory enzyme kinetic behavior

This section mainly builds upon classic biochemistry to define the essential building blocks of metabolic networks and to describe their interactions in terms of enzyme-kinetic rate equations. Following the rationale described in the previous section, the construction of a model is the organization of the individual rate equations into a coherent whole the dynamic system that describes the time-dependent behavior of each metabolite. We proceed according to the scheme suggested by Wiechert and Takors [97], namely, (i) to define the elementary units of the system (Section III. A) (ii) to characterize the connectivity and interactions between the units, as given by the stoichiometry and regulatory interactions (Sections in.B and II1.C) and (iii) to express each interaction quantitatively by... 

The activity of allosteric enzymes is adjusted by reversible binding of a specific modulator to a regulatory site. Modulators may be the substrate itself or some other metabolite, and the effect of the modulator may be inhibitory or stimulatory. The kinetic behavior of allosteric enzymes reflects cooperative interactions among enzyme subunits. 

Possible kinetic behavior of regulatory enzymes, (a) Plot of Vq versus [S]oi (1) sigmoidal (2) hyperbolic and (3) apparent hyperbolic (b) the same data plotted in double-reciprocal form. 

Therefore, from Prob. 5.28, Rg = (81) . Hence, if n > 1, then RgKinetic Behavior of Regulatory Enzymes, the enzyme is said to be positively cooperative. 

We have considered only one function of an enzyme, namely, catalysis. An equally important function is to regulate metabolic fluxes. The kinetic behavior of regulatory enzymes can be quite complex the initial velocities are often not hyperbolic functions of substrate concentrations, and the binding of nonsubstrate metabolites can have profound kinetic effects. This fascinating subject is beyond the scope of this book, but many comprehensive reviews are available [31-34]. 

It is interesting to note that this sigmoidal character of enzyme kinetics plays an essential role in regulation. Most of the regulatory enzymes in the metabolic pathways of amino acid biosyntheses and in carbohydrate metabolism exhibit such behavior, with the result that the kinetics can change in the presence of effectors (intermediary metabolities) from sigmoid to hyperbolic (see glycolysis oscillations. Sect. 5.2.1). 

A very distintive characteristic of the regulatory phenomenon already described is that the observed changes of the kinetic parameters require the integrity of the membrane, which means that the modification of the fatty acid composition change the behavior of the enzyme when membrane lipids are structuraly organized. This work shows that complementary information could be obtained from the studies of allosteric behavior and temperature-dependent activity... 

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