The Regulation of Enzymatic Activity and Metabolism

Living cells must operate with controls that provide a stable environment and a relatively constant supply of materials needed for biosynthesis and for meeting the energy needs of cells. They must also be responsive to changes in their environment and must be able to undergo mitosis and reproduce when appropriate. 

The necessary control of metabolism and of growth is accomplished largely through mechanisms that regulate the locations, the amounts, and the catalytic activities of enzymes. The purpose of this chapter is to summarize these control mechanisms and to introduce terminology and shorthand notations that will be used throughout this book. Many of the control elements considered are summarized in Fig. 11-1. 

Metabolic control can be understood to some extent by focusing attention on those enzymes that catalyze rate-limiting steps in a reaction sequence. Such pacemaker enzymes1-4 are often involved in reactions that determine the overall respiration rate of a cell, reactions that initiate major metabolic sequences, or reactions that initiate branch pathways in metabolism. Often the first step in a unique biosynthetic pathway for a compound acts as the pacemaker reaction. Such a reaction may be described as the committed step of the pathway. It usually proceeds with a large decrease in Gibbs energy and tends to be tightly controlled. Both the rate of synthesis of the enzyme protein and the activity of the enzyme, once it is formed, may be inhibited by feedback inhibition which occurs when an end product of a biosynthetic pathway accumulates 

Some catabolic reactions depend upon ADP, but under most conditions its concentration is very low because it is nearly all phosphorylated to ATP. Reactions utilizing ADP may then become the rate-limiting pacemakers in reaction sequences. Depletion of a reactant sometimes has the effect of changing the whole pattern of metabolism. Thus, if oxygen is unavailable to a yeast, the reduced coenzyme NADH accumulates and reduces pyruvate to ethanol plus C02 (Fig. 10-3). The result is a shift from oxidative metabolism to fermentation. 

Pacemaker enzymes are often identified by the fact that the measured mass action ratio, e.g., for the reaction A + B — P + Q, the ratio [P][Q]/[A][B], is far 

In spite of its usefulness, fhe pacemaker concept is oversimplified. If is often impossible to identify a specific pacemaker enzyme. When bofh catabolism and biosynthesis occur (e.g., as in the scheme in Fig. 11-2) it may be more useful to model fhe entire system with a computer than to try to identify pacemakers. If is also important to realize that reaction rates may be 

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