Each metabolic pathway has a committed step. For example in glycolysis, the committed step often is the reaction catalyzed by phosphofructokinase, or PFK. Once the substrate is converted to product, the cell must metabolize it. The cell no longer has the option to convert it to another sugar or to store it.

The committed step has a large, negative free energy change associated with it. Negative free energy changes tell us that the reaction is spontaneous in the forward direction. This means that the committed step is essentially irreversible. The enzyme activity of the committed steps is regulated. For example, multiple activators and inhibitors allosterically regulate PFK activity. Other regulated steps also have large, negative free energy changes. The remaining unregulated steps occur near equilibrium with free energy changes that are near zero. These steps are reversible, which means that the reaction may proceed in either the forward or the reverse direction. The committed step is like a valve in a pipeline. It controls what flows through it.

One of the reasons the PFK reaction is spontaneous with a large negative free energy change is because it’s coupled to the hydrolysis of ATP. The addition of orthophosphate to this sugar doesn’t spontaneously occur. ATP hydrolysis is highly exergonic. When these two reactions are coupled, the overall reaction is now favorable and proceeds in the forward direction. Many of the reactions needed to keep an organism alive would not occur without the input of energy in the form of coupled reactions.

Anabolic and catabolic pathways that make or break down a particular molecule must be different. This is because a pathway can only be spontaneous in one direction. For example, the metabolic pathway that degrades glucose is not identical to the pathway that synthesizes it. Glucose is synthesized in a process called gluconeogenesis. The three regulated steps in glycolysis are different from those in gluconeogenesis. Recall that in glycolysis, these are the three steps with large negative free energy changes. The reactions have to be different in order for them to be spontaneous in the opposite direction. This is accomplished by changing how these steps are coupled to exergonic reactions like the hydrolysis of ATP. In addition, since both degradative and synthetic reactions can occur simultaneously in the cell, they must be separately regulated.

The cell also controls opposing activities by isolating them in different compartments or organelles. For example, fatty acid oxidation occurs in the mitochondrial matrix, whereas fatty acid biosynthesis takes place in the cytosol.

Cells have developed highly integrated networks of biochemical reactions. Organisms must be able to respond appropriately to changing concentrations of nutrients and environmental conditions. All metabolic pathways must work together in order for an organism to reproduce and survive.

Copyright 2006 The Regents of the University of California and Monterey Institute for Technology and Education