Chemotrophic Energy

Metabolism:

Glycolysis and

Fermentation

Chapter 9

Becker’s The World of Cell

Metabolic Pathways

Metabolic pathways in cells are

usually either anabolic (synthetic) or

catabolic (degradative).

Catabolic reactions provide the

energy necessary to drive the

anabolic reactions.

ATP: The Universal Energy Coupler

ATP is useful for storing chemical energy in cells

because its terminal anhydride bond has an

intermediate free energy of hydrolysis. This allows ATP to

serve as a donor of phosphate groups to a number of

biologically important molecules such as glucose. It also

allows ADP to serve as an acceptor of phosphate

groups from molecules such as PEP.

ATP Hydrolysis Is Highly Exergonic Because of

Charge Repulsion and Resonance Stabilization

Chemotrophic Energy Metabolism

Most chemotrophs derive the energy needed to

generate ATP from the catabolism of organic nutrients

such as carbohydrates, fats, and proteins. They do so

either by fermentative processes in the absence of

oxygen or by aerobic respiratory metabolism in the

presence of oxygen.

Although glycolysis may seem overly complex, it

represents a mechanism by which glucose can be

degraded in dilute solution at temperatures compatible

with life, with a large portion of the free energy yield

conserved as ATP.

Biological Oxidations Usually Involve the Removal of Both Electrons

and Protons and Are Highly Exergonic

Coenzymes Such as NAD Serve as Electron Acceptors in Biological

Oxidations

Glycolysis and Fermentation: ATP Generation

Without the Involvement of Oxygen

Using glucose as a prototype substrate, catabolism

under both anaerobic and aerobic conditions begins

with glycolysis, a ten-step pathway that converts

glucose into pyruvate. In most cases, this leads to the

production of two molecules of ATP per molecule of

glucose.

In the absence of oxygen, the reduced coenzyme

NADH generated during glycolysis must be reoxidized at

the expense of pyruvate, leading to fermentation end-

products such as lactate or ethanol plus carbon

dioxide.

Alternative Substrates for Glycolysis

Although usually written with glucose as the starting

substrate, the glycolytic sequence is also the

mainstream pathway for catabolizing a variety of

related sugars, such as fructose, galactose, and

mannose.

Glycolysis is also used to metabolize the glucose-1-

phosphate derived by phosphorolytic cleavage of

storage polysaccharides such as starch or glycogen.

FIGURE 9-11 Pathways for Glycolysis and Gluconeogenesis Compared. The pathways for glycolysis (left) and gluconeogenesis (right) have nine intermediates and seven enzyme-

catalyzed reactions in common. The three essentially irreversible reactions of the glycolytic pathway (in green shading) are circumvented in gluconeogenesis by four bypass reactions (in yellow shading). Gluconeogenesis, on the other hand, is an anabolic pathway, requiring the coupled hydrolysis of six phosphoanhydride bonds (four from ATP, two from GTP) to drive it in the direction of glucose formation. The enzymes

that catalyze the bypass reactions are shown in gold and are identified in the box. In animals, glycolysis occurs in muscle and various other tissues, whereas gluconeogenesis occurs mainly in the liver and to a lesser degree in

the kidneys.

Gluconeogenesis

Gluconeogenesis is, in a sense, the opposite of glycolysis because it is the pathway used by some cells to synthesize glucose from three- and four-carbon starting materials such as pyruvate. However, the gluconeogenic pathway is not just glycolysis in reverse.

The two pathways have seven enzyme-catalyzed reactions in common, but the three most exergonic reactions of glycolysis are bypassed in gluconeogenesis by reactions that render the pathway exergonic in the gluconeogenic direction by the input of energy from ATP and GTP.

The Regulation of Glycolysis and Gluconeogenesis

Glycolysis and gluconeogenesis are regulated by

modifying the activity of enzymes that are unique to

each pathway. These enzymes are regulated by one or

more key intermediates in aerobic respiration, including

ATP, ADP, AMP, acetyl CoA, and citrate.

An important allosteric regulator of both glycolysis and

gluconeogenesis is fructose-2,6-bisphosphate. Its

concentration depends on the relative kinase and

phosphatase activities of the bifunctional enzyme PFK-2.

PFK-2 in turn is regulated by the hormones glucagon

and epinephrine via their effects on the cyclic AMP

concentration in cells.

Novel Roles for Glycolytic Enzymes

In addition to their roles as catalysts, several well-known

glycolytic enzymes have recently been shown to play

regulatory roles in cells, affecting processes such as cell

division, programmed cell death, and cancer cell

migration.