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The regulatory effects exercised by substrates through mass action generally influence all reactions in metabolic pathways; therefore, these control mechanisms are not very specific.
There are, however, a number of mechanisms by which specific reactions in a pathway can be regulated.
In one such mechanism, enzymes catalyzing specific reactions of the pathway are influenced by the type and amount of certain regulatory metabolites that are present.
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These enzymes are called allosteric enzymes because their catalytic activity is modified when specific metabolites, called allosteric effectors, are bound to a site on the enzyme other than the active site.
If the metabolite has an inhibitory effect, it is called a negative effector; if its effects are stimulatory, then it is called a positive effector. Some of the more common allosteric effectors are listed in Table 11-2.
Feedback Inhibition:
Inhibitory allosteric effects are caused when the product of a reaction sequence binds to an allosteric site of an enzyme that catalyzes a reaction at the beginning of a linear pathway or at the branch point of a branched pathway (Figs. 11-7a and 11-7b).
Binding of the effector to the enzyme causes a change in the configuration of the enzyme (called an allosteric transition) and this reduces the catalytic activity of the enzyme. Thus, as the end product of a reaction sequence begins to accumulate, more and more of the enzyme catalyzing the early stage of the reaction pathway leading to that product is rendered inactive.
In this way, the rate of formation of the end product is dramatically reduced. Where branches occur in a metabolic pathway, the end product of one branch usually affects the enzyme at the branch point leading to that product (Fig. 11-7b). This type of inhibition is called feedback inhibition or end product inhibition.
Feedback Stimulation:
Positive effectors generally act in one of two ways—by feedback stimulation or feed-forward stimulation. In feedback stimulation, the effector may be the end product of one branch of a pathway that combines with and stimulates the enzyme catalyzing the reaction at the branch point leading into the other pathway (Fig. 11-7c).
In other words, the reactions leading to the synthesis of the positive effector are attenuated, while the reactions that lead to the synthesis of an alternative product are enhanced.
Feed forward Stimulation:
In feed forward stimulation, the initial substrate of a pathway (or an early intermediate in the pathway) stimulates the activity of an enzyme further along the metabolic pathway (Fig. 11-7d). When an allosteric enzyme is affected by one effector it is said to be monovalent.
However, some allosteric enzymes may bind two or more effectors and are termed polyvalent. A single allosteric enzyme may possess sites that combine with either negative or positive effectors, and these effectors may compete with each other for the same allosteric site or be bound at different sites on the enzyme.
