Regulation of Enzymes by Effector Molecules

The regulation of the activity of enzymes by the binding of effector molecules is a ubiquitous and general principle for the fine timing and control of metabolic activity. Effector molecules are often low molecular weight organic compounds. Proteins and metal ions can also exercise the function of effectors. The effector molecules bind specifically to the enzymes and the binding results in inhibition or stimulation of enzymatic activity. 

For the regulation of metabolic pathways metabolites are often used which are a product of that pathway. The basic strategy for the regulation is exemplified in the mechanisms employed in the biosynthetic and degradation pathways of amino acids, purines, pyrimidines, as well as in glycolysis. In most cases a metabolite (or similar molecule) of the pathway is utilized as the effector for the activation or inhibition of enzymes in that pathway. 

Enzymes that are regulated by effector molecules in an allosteric maimer possess, apart from the binding site for the substrate, a specific binding site for the effector molecule. The binding of effector molecules to the effector site leads to a shift in equilibrium between the various conformations and thus to a change in activity (see 2.3). 

The pathway from enzyme-bound substrate to the transition state involves changes in the electronic configuration and geometry of the substrate. The enzyme itself is also not static. The ability to tightly bind the transition state requires flexibility in the active site. Such flexibility has been experimentally demonstrated in many cases. A corollary to this is that the effectivity of enzyme catalysis can easily be influenced and regulated by conformational changes in the enzyme. An extensive consideration of the mechanisms of enzymes can be found in the works by J. Kraut (1988) and A. Fersht (1998). 

The ability of proteins to exist in different conformations is termed allostery (see Section2.3). Allosteric enzymes can assume various conformations, which differ in catalytic activity and/or substrate-binding capacity. 

Effector molecules bind to an enzyme of a metabolic pathway and modify its activity in a concentration-dependent manner. This regulation serves to adjust the level of production of metabolites by the pathway to the current needs in the cell. The regulatory signal of such a feedback regulation strategy is the concentration of the final product or of an intermediate. In feedback inhibition, if the concentration of a particular product exceeds a certain level, then the product occupies the active site of the 

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