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Landmark discoveries in the trail from chemistry to cellular biochemistry, with particular reference to mileposts in research on bioenergetics

Molecular oxygen was discovered in 1775 by Joseph Priestley. He also made the important observations that oxygen is produced by plants and that gases (O2 and CO2) mediate the interdependence of plant and animal life. The biological experiments of Priestley dealt with aerobes, the most advanced forms of life. It was the research of Louis Pasteur, however, on fermentation of sugar by anaerobic microbes that provided a system that was the first to reveal significant clues to the biochemistry of bioenergetics. Analysis of the detailed mechanism of anaerobic sugar fermentation by yeast during the first third of the 20th century and the later study of energy‐yielding aerobic respiration and energy conversion in photosynthesis required development of many new techniques. These became the tools that were exploited to yield the basic outlines of cell biochemistry. Included were chromatography, metabolic gas manometry, spectrophotometry, the use of stable and radioactive isotopes as tracers of intermediary metabolism, and procedures for purification of proteins and other macromolecules. Noteworthy advances included discovery and characterization of the (Krebs) tricarboxylic acid cycle, “activated” intermediates such as acetyl coenzyme A, electron carriers and coenzymes necessary for energy conversion and reductive biosynthesis, ATP (the universal energy “currency”) and a multitude of enzymes involved in catabolic and biosynthetic metabolism.