Glycolysis

Simply put, glycolysis (glyco = sugar; lysis = splitting) splits a 6‐carbon sugar, glucose, into two molecules of 3‐carbon pyruvate in a series of steps, each catalyzed by a particular enzyme. The energy of the sugar molecule is released in stages and transferred to adenosine triphosphate (ATP) and the reduced coenzyme nicotinamide adenine dinucleotide (NADH), each of which are then available for other energy‐requiring metabolic processes. (Note: Pyruvic acid formed in the reactions dissociates to pyruvate plus H +; the acid and the pyruvate exist together in equilibrium, and so the names “pyruvate” and “pyruvic acid” are used interchangeably by textbook authors.)

First steps (preparatory, energy-using stages)

The energy needed to start the reaction comes from an ATP molecule that is added, together with a phosphate group, to one of the sugar carbons, thereby energizing the sugar to glucose‐6‐phosphate.

The molecule is restructured, a second ATP enters, binding another phosphate group to a different carbon atom, and the 6‐carbon energized sugar molecule splits into two 3‐carbon molecules, each with a phosphate group consisting of dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3‐phosphate (PGAL).

Final steps (energy-releasing phase)

DHAP converts to PGAL. There are now two molecules of PGAL going forward. Two almost simultaneous reactions occur next: an oxidation and a phosphorylation. Energy is harvested in the oxidation of PGAL (H atoms and their electrons are removed), and the coenzyme NAD + is reduced (H atoms and electrons added) to form NADH, a high‐energy compound.

The phosphorylation, using some of the oxidation energy, attaches an inorganic phosphate group (P i) to the carbon ring (the bond energy is similar to that of the high energy bonds of ATP). The substrate is now 1,3‐bisphosphoglycerate, with two phosphate groups attached.

A phosphate group is released to phosphorylate a molecule of ADP, forming a molecule of ATP. This kind of phosphorylation—formation of ATP by transferring a P i from a metabolic intermediate compound—is called substrate‐level phosphorylation. Since there are two PGAL molecules from each glucose molecule, two ATPs are formed at this stage. Two ATPs were needed to activate the pathway, so at this point the energy use and production are equal.

The substrate molecule is restructured: The remaining P i group is moved to another binding site in the molecule, and a molecule of water is removed resulting in a high‐energy, phosphorylated compound being formed (phosphoenolpyruvate).

A second substrate‐level phosphorylation takes place; the P i is moved to ADP, and the second molecule of ATP is formed.

The result of all of these reactions is: two molecules of 3‐carbon pyruvate, four ATPs, and two NADHs for each molecule of glucose. The net gain of ATP, however, is only two molecules of ATP since two molecules were used to initiate the process. The two pyruvate molecules retain about 80 percent of the energy of the glucose molecule, and the two NADH molecules also are used in later energy‐requiring metabolic reactions in the mitochondria. (Six molecules of ATP can be produced by re‐oxidizing them back to NAD +.)

Remember that the above reactions take place in the cytosol of cells and are catalyzed by enzymes specific for each reaction. Note that oxygen is not used in any of the above reactions. Glycolysis is an anaerobic process.