5.3: Enzyme Regulation

We noted that some enzymes are regulated, which just means that there are factors in the cell that can slow down or speed up their rate of catalysis. In this way the cell can respond quickly to the metabolic needs reflected by the intracellular levels of these factors. Factors that slow down catalysis are inhibitors. Those that speed up catalysis are called activators.

In addition to responding to intracellular molecular indicators of the metabolic status of the cell, enzymes may also be inhibited by drugs, poisons, or changes in the chemical milieu (e.g., pH). Since cellular reactions occur as part of biochemical pathways, regulating a single enzyme can affect an entire pathway (e.g., Figure 5.4).

Figure 5.4: Reaction products in a biochemical pathway can alter the rate of synthesis of the pathway's final products. In this generic pathway, the end-product (D) accumulates (far right). At some point, excess E binds to the allosteric regulatory sites on enzyme 1 at the left, blocking the formation of B, an intermediate product. This kind of feed-back inhibition prevents a wasteful overproduction of D.

This biochemical pathway will produce substance E. Under normal conditions, another series of metabolic reactions would consume E. However, if the cell no longer needs so much E, it will accumulate in the cell. If there is an excess of E in the cell, some of the excess might bind to one of the enzymes. In the pathway shown, E binds to enzyme 1. This binding causes an allosteric change in the enzyme, inhibiting catalysis and slowing down the entire pathway.

In this example of allosteric regulation, the inhibitory regulation of enzyme 1 evolved to control the rate of production of substance E. This common mode of allosteric regulation is called feedback inhibition. Enzymes can be regulated precisely because they can be bent out of shape (or into shape for that matter!). Some small metabolites are chemical information when they accumulate in cells and can communicate cellular metabolic status. The result is a decrease or increase in enzyme activities to achieve an appropriate cellular response.

Whether an activator or an inhibitor of enzyme catalysis, regulatory molecules typically bind to enzymes at allosteric regulatory sites, causing local conformational changes in the enzyme, which are transmitted to the active site. Enzyme inhibition would occur if a change in shape reduced the affinity of the enzyme for a substrate—or if it reduced the rate of bond rearrangements after the substrate had already entered the active site. Enzyme activation would occur if the allosteric effect were to increase this affinity and/or catalytic rate. The mechanism of allosteric regulation of enzyme activity is shown in Figure 5.5.

Figure 5.5: Levels of small metabolic chemicals (metabolites) can reflect and control a cell’s metabolic status. Such metabolites, called allosteric effectors, have an affinity for regulatory sites on an enzyme (shown at the left), causing conformational (shape) changes in its active site (seen at the right). Allosteric regulation can reduce or increase the affinity of enzyme and substrate, either inhibiting catalysis, as suggested here, or stimulating it.

148-2 Allosteric Regulation of Enzyme Activity