The first indication that phosphorus is important for life came from the experience that plants take it up from the substances in the soil. They incorporate it in their body substance. What makes phosphorus so important that they cannot grow without it? The next insight was that animals acquire it from their plant food. It is then found in bones, in fat and nerve tissue, in all cells and particularly in the cell nuclei. What are its functions there? The answers to such questions were developed from the study of a long-known process, the conversion of carbohydrates into carbon dioxide and alcohol by yeast. It started with Eduard Buchner's discovery of 1890, that fermentation is produced by a preparation from yeast in which all living cells have been removed. When yeast is dead-ground and pressed out, the juice still has the ability to produce fermentation. 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: ^ NH_{2} / \\ | / \\ N ^ || |-CONH_{2} //\ / \\ || | | || N \ // | || | N_{+} N--+ | | | \// | | N H--C------+ H--C------+ | | | | H--C--OH | H--C--OH | | O | O H--C--OH | H--C--OH | | | | | H--C------+ O O H--C------+ | || || | CH_{2}--O--P--O--P--O--CH_{2} | | O- OH Coenzyme I [Illustration: 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.]