Sudden and dramatic changes in cellular activity (e.g., conduction of nerve impulses by a nerve cell or the contractions of a muscle cell) demand rapid increases (or decreases) in the cellular level of particular metabolic intermediates.
The binding of effectors at the regulatory sites of allosteric enzymes acts to quickly increase (or decrease) the level of enzyme activity and in so doing quickly alter the rate at which substrate is converted to product by that enzyme.
Such mechanisms for regulating the flux of a metabolic pathway through a particular reaction may be augmented by the use of substrate cycles.
Consider the scheme shown in Figure 8-27. Metabolic intermediate A is the product of enzymes El and E4 and is the substrate of enzyme E2, an allosteric enzyme influenced by the binding of a positive effector. Intermediate B is the product of allosteric enzyme E2 and is the substrate of enzymes E3 and E4. Thus, A and B form, a substrate cycle. Substrate cycles such as the one shown in Figure 8-27 are also referred to as “futile cycles” because in the absence of any regulation the cycle would simply go around and around, dissipating energy (in the form of wasted ATP).
Suppose that under “resting” cellular conditions the cycle is at idling speed and there are moderate fluxes in both the forward and reverse directions, but the net flux in the direction of B is very low (i.e., approaching zero) because most of B produced by E2 is converted back to A by E4. In such an instance, even a small increase in the activity of E2 (through binding of a positive effector) would dramatically increase the net flux in the direction of B.
The magnitude of the effect may be illustrated by assigning some hypothetical values to these fluxes. For example, if under resting conditions the A → B flux is 100 and the B →A flux is 98, then the net flux in the direction A→B would be 2. An increase in the A→B flux from 100 to 110 (a 10% increase) could increase the net flux in the A -+B direction from 2 to 12 (a 600% increase).
This, of course, presumes that the increase in the rate at which B is being produced does not cause an increase in the activity of E4. The latter could readily be avoided if (a) E4 were already at saturation kinetics, (b) E3 were activated so that there is little or no increase in the concentration of B, or (c) E4 is inhibited by the same effector that stimulates E2.
Catalysis by RNA:
The synthesis of RNA destined to be incorporated into a cell’s ribosomes involves a series of processing stages in which a large polyribonucleotide is cleaved at specific points to form a smaller product. Though most RNA processing involves enzymes called endonucleases, it has recently been discovered that one of these cleavages (at least in the protist Tetrahymena) is catalyzed by RNA itself; that is, the RNA molecule catalyzes the hydrolysis of one of its own phosphodiester linkages. This RNA has been called ribozyme to emphasize these enzymelike properties.
Ribozyme may be an example of a primordial bio- catalyst; certainly, its discovery lends support to a popular notion that nucleic acid synthesis proceeded by a self-replicating process prior to the evolution of enzymes as biocatalysts.