Glycolysis is the metabolic pathway that converts glucose into pyruvate and, in most organisms, occurs in the liquid part of cells known as the cytosol. This process is so fundamental that it likely began before life itself fully formed, occurring in the oxygen-free conditions of the Archean oceans. The reactions that make up glycolysis can take place without enzymes, catalyzed instead by metal ions, suggesting this is a plausible prebiotic pathway for abiogenesis. The most common type of glycolysis is the Embden, Meyerhof, Parnas pathway, named after Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas, who pieced together the puzzle over nearly a century of scientific inquiry. While other pathways exist, such as the Entner, Doudoroff pathway, the Embden, Meyerhof, Parnas pathway remains the central focus of modern biochemistry because it is the universal engine of cellular energy.
The Century-Long Discovery
The modern understanding of the pathway of glycolysis took almost 100 years to fully learn, requiring the combined results of many smaller experiments. The first steps began in the 1850s when French scientist Louis Pasteur investigated why wine sometimes turned distasteful instead of fermenting into alcohol. His experiments showed that alcohol fermentation occurs by the action of living microorganisms, yeasts, and that glucose consumption decreased under aerobic conditions, a phenomenon now known as the Pasteur effect. In the 1890s, Eduard Buchner revolutionized biochemistry by demonstrating that the conversion of glucose to ethanol was possible using a non-living extract of yeast, proving that enzymes within the extract were responsible for the reaction. This allowed later scientists to analyze the pathway in a controlled laboratory setting. Between 1905 and 1911, Arthur Harden and William Young discovered the regulatory effects of ATP on glucose consumption and identified fructose 1,6-bisphosphate as a key intermediate. By the 1920s, Otto Meyerhof linked these pieces together, extracting enzymes from muscle tissue to artificially create the pathway from glycogen to lactic acid. It was not until the 1940s that Gustav Embden, Meyerhof, and many other biochemists had finally completed the puzzle of glycolysis.The Investment and Payoff
The glycolysis pathway can be separated into two distinct phases: the investment phase and the yield phase. The first five steps are regarded as the preparatory phase, wherein ATP is consumed to convert the glucose into two three-carbon sugar phosphates. Once glucose enters the cell, the first step is phosphorylation by hexokinases to form glucose 6-phosphate, which consumes ATP but acts to keep the glucose concentration inside the cell low. This phosphorylation also blocks the glucose from leaking out because the cell lacks transporters for glucose 6-phosphate. The energy expenditure of another ATP in the third step is justified because it makes the reaction irreversible and destabilizes the molecule, allowing the hexose ring to be split by aldolase into two triose sugars. The second half of glycolysis is known as the pay-off phase, characterized by a net gain of the energy-rich molecules ATP and NADH. Since glucose leads to two triose sugars in the preparatory phase, each reaction in the pay-off phase occurs twice per glucose molecule, yielding 2 NADH molecules and 4 ATP molecules, leading to a net gain of 2 NADH molecules and 2 ATP molecules from the glycolytic pathway per glucose.