Spoiled French wine helped uncover how every cell burns sugar
In the 1850s the French wine trade wanted to know why some batches went sour instead of turning to alcohol. Louis Pasteur's answer, that living yeasts drive fermentation, launched nearly a century of work on glycolysis, the ten-step pathway that splits glucose for energy and may be old enough to predate life itself.
Glycolysis converts glucose into pyruvate, usually in the fluid part of the cell, the cytosol, and captures some of the released energy as ATP and NADH. It runs in two phases: an investment stage that spends ATP, then a payoff stage that produces more than was spent. The standard version is the Embden-Meyerhof-Parnas pathway, named for Gustav Embden, Otto Meyerhof and Jakub Karol Parnas, though other routes such as the Entner-Doudoroff pathway also count.
The pathway's ubiquity suggests great age. Its reactions, and those of the parallel pentose phosphate pathway, can proceed in oxygen-free water resembling the Archean oceans, driven by metal ions and without any enzymes, which makes glycolysis a plausible chemical route toward the origin of life. With oxygen available, eukaryotic cells pass pyruvate on to the citric acid cycle and electron transport chain for far more ATP. Without oxygen, glycolysis is the only way eukaryotes can make ATP, so many organisms evolved fermentation, producing ethanol or lactic acid, to regenerate NAD+ and keep the pathway running.
Pieces came together slowly. Pasteur also noticed that yeast consumes less glucose when oxygen is present, now called the Pasteur effect. In the 1890s Eduard Buchner showed that a non-living yeast extract could still turn glucose into ethanol, proving enzymes were doing the work and opening the way to controlled lab studies.
Between 1905 and 1911, Arthur Harden and William Young found that ATP regulates glucose use during fermentation. Watching carbon dioxide output from yeast juice rise and then stall, they discovered that adding inorganic phosphate restarted it, leading them to isolate fructose 1,6-bisphosphate as an intermediate. A further experiment separated purified yeast juice, which could not ferment, from boiled extract, in which proteins were destroyed. Mixed together they worked, revealing that fermentation needs both heat-sensitive enzymes and heat-stable, non-protein helpers such as ATP and NAD+.
Source: Glycolysis
