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Fritz Lipmann

The introductory quote reproduced from Franklin Harrod's "The Vital Force" exemplifies the focus of the EXBAN website. It emphasizes the confusion generated in the minds of students by terms such as "high energy phosphates." The misconceptions surrounding the molecular basis of energy transformation in biological systems that persist today are associated with semantics introduced many decades ago. Terms such as "energy stored in bonds", "the high energy phosphate bond", and phrases such as the "role of phosphate bond energy in driving anabolic processes" have been responsible for the persistent misconception that bond breaking is exothermic. The introduction by Fritz Lipmann of terms such as "the high energy phosphate bond" which he denoted with his famous squiggle (~), and "phosphate bond energy", served to emphasize the origins of energy transformations in the cell, but at the same time has been the source of considerable confusion. However, Fritz Lipmann's focus on the role of phosphates in the energy metabolism in the cell, in many ways, revolutionized biochemical thinking. He was a pioneer and a giant in linking descriptive biochemistry with energy transformations in the cell. It would be highly unfair to stress the confusion that has arisen in chemistry as well as in biology due to the semantics he employed, without drawing attention to the enormous contributions he made, particularly in the area directly connected with the terminology that is under question.

With degrees in medicine and chemistry Fritz Lipmann spent his life as a researcher in biochemistry. He was awarded the Nobel prize in medicine and physiology along with Dr. Hans Krebs in 1953 for his discovery of coenzymeA. Descriptions of his life and scientific career can be found in a number of references on the Web, as well as in volumes dedicated to him over the years. His scientific life is traced out in his own contribution "Wanderings of a Biochemist". It was in a 1941 review article published in Advances in Enzymology in which Lipmann emphasized the significance of phosphates and the transfer of phosphate groups in bringing about energy transformations in cells as well as introducing "the high energy phosphate bond", the squiggle ~ and "phosphate transfer potential" in discussing these transformations. A lengthy review article of a similar nature was published the same year by H. Kalckar in Chem. Reviews. Both of these articles drew attention to the thermodynamic instability of those molecules that are said to possess "high energy" and did not emphasize the significance of bond breaking and making in exergonic, or endergonic reactions.

It is an unfortunate casualty of today's crowded biochemistry and chemistry curricula that students do not have the time to develop a greater appreciation of their fields from a historical perspective. In addition to the references provided here, the book by Joseph Fruton contains valuable insights into the development of this aspect of biochemistry.

Lipmann, F. (1941) Metabolic Generation and Utilization of Phosphate Bond Energy. Adv. Enzym. 1, 99-162.

Kalckar, H. M, (1941) The Nature of Energetic Coupling in Biological Synthesis. Chem. Reviews 28, 71-178.

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