Glycolysis, a series of enzymatic steps in which the six-carbon glucose molecule is degraded to yield two three-carbon pyruvate molecules, is a central catabolic pathway in plants, animals and many microorganisms.
In a sequence of 10 enzymatic steps, energy released from glucose is conserved by glycolysis in the form of adenosine triphosphate (ATP). So central is glycolysis to life that its sequence of reactions differs among species only in how its rate is regulated, and in the metabolic fate of pyruvate formed from glycolysis.
In aerobic organisms (some microbes and all plants and animals), glycolysis is the first phase of the complete degradation of glucose. The pyruvate formed by glycolysis is oxidized to form the acetyl group of acetylcoenzyme A, while its carboxyl group is oxidized to CO2. The acetyl group is then oxidized to CO2 and H2O by the citric acid cycle with the help of the electron transport chain, the site of the final steps of oxidative phosphorylation of adenosine diphosphate molecules to high-energy ATP molecules.
In some animal tissues, pyruvate is reduced to lactate during anaerobic periods, such as during vigorous exercise, when there is not enough oxygen available to oxidize glucose further. This process, called anaerobic glycolysis, is an important source of ATP during very intense muscle activity.
Anaerobic glycolysis also serves to oxidize glucose to lactic acid with the production of ATP in anaerobic microorganisms. Such lactic acid production by bacteria sours milk and gives sauerkraut its mildly acidic taste.
A third pathway for pyruvate produced by glycolysis produces ethanol and CO2 during anaerobic glycolysis in certain microorganisms, such as brewer's yeast—a process called alcoholic fermentation. Fermentation is an anaerobic process by which glucose or other organic nutrients are degraded into various products to obtain ATP.
Because glycolysis occurs in the absence of oxygen, and living organisms first arose in an anaerobic environment, anaerobic catabolism was the first biological pathway to evolve for obtaining energy from organic molecules.
Glycolysis occurs in two phases. In the first phase, there are two significant events. The addition of two phosphate groups to the six-carbon sugar primes it for further degradation in the second phase. Then, cleavage of the doubly phosphorylated six-carbon chain occurs, breaking fructose 1,6-diphosphate into two 3-carbon isomers. These are fragments of the original six-carbon sugar dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.
In the second phase, the two 3-carbon fragments of the original 6-carbon sugar are further oxidized to lactate or pyruvate.
Entry into the second phase requires the isomer to be in its glyceraldehyde 3-phosphate form. Thus, the dihydroxyacetone phosphate isomer is transformed into glyceraldehyde 3-phosphate before being further oxidized by the glycolytic pathway.
Glycolysis produces a total of four ATP molecules in the second phase, two molecules of ATP from each glyceraldehyde 3-phosphate molecule. The ATP is formed during substrate-level phosphorylation-direct transfer of a phosphate group from each 3-carbon fragment of the sugar to adenosine diphosphate (ADP), to form ATP. But because two ATP molecules were used to phosphorylate the original six-carbon sugar, the net gain is two ATP.
The net gain of two ATP represents a modest conservation of the chemical energy stored in the glucose molecule. Further oxidation, by means of the reactions of the Kreb's cycle and oxidative phosphorylation are required to extract the maximum amount of energy from this fuel molecule.
Atkinson, D.E. Cellular Energy Metabolism and Its Regulation. New York: Academic, 1977.
Lehninger, A.L. Principles of Biochemistry. New York: Worth Publishers, Inc., 1982.