Regulation of Enzyme Activity

Enzymes function in assembly line-like fashion to catalyze the thousands of reactions occurring in cells each second. Coordinating and regulating enzymatic activities is essential for efficient functioning of cells. Several control mechanisms that do not involve covalent modification of the enzymes are possible:

> Substrate level control - In this control mechanism, high levels of the product of a reaction inhibit the ability of the small amounts of substrate present to react. An example is the first step in glycolysis, catalyzed by hexokinase. It is inhibited by the product of its action, glucose-6-phosphate. If glycolysis is blocked for any reason, glucose-6-phosphate accumulates.

> Feedback control - In this mechanism, the product of a series of reactions (like in an assembly line) inhibits the action of an earlier step in the process (usually the first step). Feedforward regulation occurs when a molecule in an assembly line reaction activates an enzyme ahead of it in the pathway.

> Allosteric enzymes - These enzymes are invariably multisubunit proteins, with multiple active sites. They exhibit cooperativity in substrate binding (homoallostery) and regulation of their activity by other, effector molecules (heteroallostery).

> > Homoallostery - The effects of cooperative substrate binding on enzyme kinetics are shown in Figure 11.32. Binding of one substrate favors binding of additional substrates. Cooperative binding favors reduction of K M for the binding of substrates after the initial one. Figure 11.33 shows the effect of extreme homoallostery. At concentrations of S below a critical point, [S]c, the enzyme is almost inactive, but then changes activity rapidly with concentrations of S greater than [S]c.

> > Heteroallostery - This type of allosteric control involves heteroallosteric effectors which may be either inhibitors or activators of binding. If an enzyme can exist in two conformational states, T and R, that differ dramatically in the strength with which substrate is bound or which differ significantly in the catalytic rate, then the kinetics of the enzyme can be controlled by any other substance that, in binding to the protein, shifts the T<=>R equilibrium. Allosteric inhibitors shift the equilibrium toward T and activators shift it toward the R state.

> > Figure 11.34 illustrates how heteroallosteric control of an enzyme affects the shape of a V-vs-[S] curve. Note that shifts toward the R state (activators) increase the velocity for a given substrate concentration, whereas shifts toward the T state have the opposite effect.

See also: Covalent Modifications to Regulate Enzyme Activity, Aspartate Carbamoyltransferase, Hexokinase

INTERNET LINK: Properties of Allosteric Enzymes