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Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002.

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Biochemistry. 5th edition.

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Chapter 16Glycolysis and Gluconeogenesis

Glycolysis produces energy.


Glycolysis produces energy. Michael Johnson sprints to another victory in the 200-meter semifinals of the Olympics. Johnson, like anyone who sprints, requires a source of energy that can be rapidly accessed. The anaerobic metabolism of glucose—the (more...)

The first metabolic pathway that we encounter is glycolysis, an ancient pathway employed by a host of organisms. Glycolysis is the sequence of reactions that metabolizes one molecule of glucose to two molecules of pyruvate with the concomitant net production of two molecules of ATP. This process is anaerobic (i.e., it does not require O2) inasmuch as it evolved before the accumulation of substantial amounts of oxygen in the atmosphere. Pyruvate can be further processed anaerobically (fermented) to lactate (lactic acid fermentation) or ethanol (alcoholic fermentation). Under aerobic conditions, pyruvate can be completely oxidized to CO2, generating much more ATP, as will be discussed in Chapters 17 and 18.

Glucose can be synthesized from noncarbohydrate precursors, such as pyruvate and lactic acid, in the process of gluconeogenesis. Although glycolysis and gluconeogenesis have some of the same enzymes in common, the two pathways are not simply the reverse of each other. In particular, the highly exergonic, irreversible steps of glycolysis are bypassed in gluconeogenesis. Both pathways are stringently controlled by intercellular and intracellular signals, and they are reciprocally regulated so that glycolysis and gluconeogenesis do not take place simultaneously in the same cell to a significant extent.

Our understanding of glucose metabolism, especially glycolysis, has a rich history. Indeed, the development of biochemistry and the delineation of glycolysis went hand in hand. A key discovery was made by Hans Buchner and Eduard Buchner in 1897, quite by accident. The Buchners were interested in manufacturing cell-free extracts of yeast for possible therapeutic use. These extracts had to be preserved without the use of antiseptics such as phenol, and so they decided to try sucrose, a commonly used preservative in kitchen chemistry. They obtained a startling result: sucrose was rapidly fermented into alcohol by the yeast juice. The significance of this finding was immense. The Buchners demonstrated for the first time that fermentation could take place outside living cells. The accepted view of their day, asserted by Louis Pasteur in 1860, was that fermentation is inextricably tied to living cells. The chance discovery of the Buchners refuted this vitalistic dogma and opened the door to modern biochemistry. Metabolism became chemistry.


Derived from the Greek stem glyk-, “sweet,” and the word lysis, “dissolution.”

Studies of muscle extracts then showed that many of the reactions of lactic acid fermentation were the same as those of alcoholic fermentation. This exciting discovery revealed an underlying unity in biochemistry. The complete glycolytic pathway was elucidated by 1940, largely through the pioneering contributions of Gustav Embden, Otto Meyerhof, Carl Neuberg, Jacob Parnas, Otto Warburg, Gerty Cori, and Carl Cori. Glycolysis is also known as the Embden-Meyerhof pathway.


A term coined by Friedrich Whilhelm Kühne in 1878 to designate catalytically active substances that had previously been called ferments. Derived from the Greek workds en, “in,” and zyme, “leaven.”

In our consideration of the glycolytic and gluconeogenic pathways, we shall examine the mechanisms of selected enzymes in some detail. Of particular interest will be the enzymes that play the most central roles in converting one type of chemical energy into another.

16.0.1. Glucose Is an Important Fuel for Most Organisms:

Image tree.jpg Glucose is an important and common fuel. In mammals, glucose is the only fuel that the brain uses under nonstarvation conditions and the only fuel that red blood cells can use at all. Indeed, almost all organisms use glucose, and most that do process it in a similar fashion. Recall from Chapter 11 that there are many carbohydrates. Why is glucose instead of some other monosaccharide such a prominent fuel? We can speculate on the reasons. First, glucose is one of the monosaccharides formed from formaldehyde under prebiotic conditions, so it may have been available as a fuel source for primitive biochemical systems. Second, glucose has a low tendency, relative to other monosaccharides, to nonenzymatically glycosylate proteins. In their open-chain (carbonyl) forms, monosaccharides can react with the amino groups of proteins to form Schiff bases, which rearrange to form a more stable amino ketone linkage. Such nonspecifically modified proteins often do not function effectively. Glucose has a strong tendency to exist in the ring formation and, consequently, relatively little tendency to modify proteins. Recall that all the hydroxyl groups in the ring conformation of β-glucose are equatorial, contributing to this high relative stability (Section 11.12.12).

16.0.2. Fermentations Provide Usable Energy in the Absence of Oxygen:

Although glycolysis is a nearly universal process, the fate of its end product, pyruvate, may vary in different organisms or even in different tissues. In the presence of oxygen, the most common situation in multicellular organisms and many unicellular ones, pyruvate is metabolized to carbon dioxide and water through the citric acid cycle and the electron-transport chain. In the absence of oxygen, fermentation generates a lesser amount of energy; pyruvate is converted, or fermented, into lactic acid in lactic acid fermentation or into ethanol in alcoholic fermentation (Figure 16.1). Lactic acid production takes place in skeletal muscle when energy needs outpace the ability to transport oxygen. Although we will consider only these two fermentations, microorganisms are capable of generating a wide array of molecules as end points to fermentation (Table 16.1). Indeed, many food products are the result of fermentations. These foods include sour cream, yogurt, various cheeses, beer, wine, and sauerkraut.


An ATP-generating process in which organic compounds act as both donors and acceptors of electrons. Fermentation can take place in the absence of O2. Discovered by Louis Pasteur, who described fermentation as “la vie sans l'air” (“life without air”).

Figure 16.1. Some Fates of Glucose.

Figure 16.1

Some Fates of Glucose.

Table 16.1. Starting and ending points of various fermentations.

Table 16.1

Starting and ending points of various fermentations.

Fermentations yield only a fraction of the energy available from the complete combustion of glucose. Why is a relatively inefficient metabolic pathway so extensively used? The fundamental reason is that oxygen is not required. The ability to survive without oxygen affords a host of living accommodations such as soils, deep water, and skin pores. Some organisms, called obligate anaerobes, cannot survive in the presence of O2, a highly reactive compound. The bacterium Clostridium perfringens, the cause of gangrene, is an example of an obligate anaerobe. Other pathogenic obligate anaerobes are listed in Table 16.2.

Table 16.2. Examples of pathogenic obligate anaerobes.

Table 16.2

Examples of pathogenic obligate anaerobes.

Facultative anaerobes can function in the presence or absence of oxygen. For instance, organisms that live in the intertidal zone, such as the bivalve Mytilus (Figure 16.2), can function aerobically, using gills when they are under water and anaerobically when exposed to the air. Such organisms display habitat-dependent anaerobic functioning, or habitat-dependent anaerobiosis. Muscles in most animals display activity-dependent anaerobiosis, meaning that they can function anaerobically for short periods. For example, when animals perform bursts of intense exercise, their ATP needs rise faster than the ability of the body to provide oxygen to the muscle. The muscle functions anaerobically until the lactic acid builds up to the point at which the fall in pH inhibits the anaerobic pathway (Section 16.2.1).

Figure 16.2. The Bivalve Mytilus.

Figure 16.2

The Bivalve Mytilus. These mussels, inhabitants of the intertidal zone, display habitat-dependent anaerobiosis. [Ed Reschke/Peter Arnold.]

  • 16.1. Glycolysis Is an Energy-Conversion Pathway in Many Organisms
  • 16.2. The Glycolytic Pathway Is Tightly Controlled
  • 16.3. Glucose Can Be Synthesized from Noncarbohydrate Precursors
  • 16.4. Gluconeogenesis and Glycolysis Are Reciprocally Regulated
  • Summary
  • Problems
  • Selected Readings

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2002, W. H. Freeman and Company.
Bookshelf ID: NBK21150


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