It is strange, but in many ways characteristic for the process of science, that the “riddle” of phosphorus in life was solved by first eliminating life. In such “lifeless” fermentations, Arthur Harden found that the conversion of sugar begins with the formation of a hexose phosphate (1904). The “ferment” of yeast, called zymase, proved to be a composite of several enzymes. Hans von Euler-Chelpin isolated one part of zymase, which remains active even after heating its solution to the boiling point. From 1 kilogram of yeast, he obtained 20 milligrams of this heat-stable enzyme, which he called cozymase and identified as a nucleotide composed of a purine, a sugar, and phosphoric acid.[36] In the years between the two World Wars, zymase was further resolved into more enzymes, one of them the coenzyme I, which was shown to be ADP connected with another molecule of ribose attached to the amide of nicotinic acid, or diphosphopyridine nucleotide:

Figure 20.—Fritz A. Lipmann (b. 1899) shared with Hans Adolf Krebs the Nobel Prize in Medicine and Physiology in 1953 for his work on coenzyme A. He discovered acetyl phosphate as the substance in bacteria, which transfers phosphate to adenylic acid.

Figure 21.—Alexander R. Todd (b. 1907) received the Nobel Prize in Chemistry in 1957 for his research on nucleotides. He determined the position of the phosphate groups in the molecule and confirmed it by synthesis of dinucleotide phosphates.

Its function is connected with the transfer of hydrogen between intermediates formed through phosphate-transferring enzymes. Fermentation proceeds by a cascade of processes, in which phosphate groups swing back and forth, and equilibria between ATP with ADP play a major role.