Harper's Illustrated Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Carbohydrate and Lipid Metabolism
Regulation of Carbohydrate Metabolism
General Principles of the Regulation of Metabolic Pathways

The regulation of reaction rates within a specific metabolic pathway is frequently achieved by altering The rate of one or perhaps two key Reactions Catalyzed by "regulatory Enzymes." Certain physicochemical factors that control the rate of an enzymatic reaction, such as Substrate Concentration (see ch. 9), are of paramount importance in regulating the overall rate of product formation in a given metabolic pathway. At the same time, other factors influencing enzyme activity, such as Temperature and pH, remain constant in warm-blooded animals and are virtually irrelevant for regulating metabolic reaction rates. (Note, however, the shift in pH along the gastrointestinal tract and its impact on Digestion; see ch. 53.)

Equilibrium and Nonequilibrium Reactions

When equilibrium is reached, the forward and reverse reactions proceed at the same rate, and consequently, the concentrations of product and substrate remain constant. Many metabolic reactions occur under precisely these conditions, meaning they are "equilibrium" reactions.

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Under steady-state conditions in vivo, the reaction can proceed from left to right due to the continuous supply of substrate and the constant removal of product D. Such a pathway could function, but it would leave little room for regulating its rate by changing enzyme activity, since increased activity would merely lead to a more rapid attainment of equilibrium.

In reality, a metabolic pathway typically features one or more "nonequilibrium" reactions, where reactant concentrations are far from equilibrium. As the reaction proceeds in a nonequilibrium state, Free energy is dissipated as heat, rendering the reaction practically irreversible.

Through such a pathway, the flux of reactants moves in a specific direction; however, without a control system, depletion would occur. The concentrations of enzymes catalyzing nonequilibrium reactions are usually low, and their activity is regulated by specialized mechanisms acting like a "one-way valve" to control the rate of product formation.

Rate-Determining Reaction of a Metabolic Pathway

A rate-determining reaction is the initial reaction in a metabolic pathway whose enzyme becomes saturated with substrate. It can be defined as a "nonequilibrium" reaction characterized by a K_m value significantly lower than the normal substrate concentration. The first reaction of Glycolysis, catalyzed by hexokinase (Fig. 22.2), serves as an example of such a rate-determining reaction.