Fritz Lipmann's landmark paper, "Metabolic Generation and Utilization of Phosphate Bond Energy," published in 1941, laid the foundation for research into concepts involving group potential and the role of group transfer in biosynthesis. Lipmann had revealed the basis for the relationship between metabolic energy production and its use, providing the first coherent picture of how living organisms operate. His discovery in 1945 of coenzyme A (CoA), which occurs in all living cells and is a key element in the metabolism of carbohydrates, fats, and some amino acids, earned him the 1953 Nobel Prize in physiology or medicine. Lipmann also conducted groundbreaking research in protein synthesis. Lipmann was an instinctual researcher with a knack for seeing the broader picture. Lacking the talent or inclination for self-promotion, he struggled early in his career before establishing himself in the world of biochemistry.
Fritz Albert Lipmann was born on June 12, 1899, in Königsberg, the capital of East Prussia (now Kaliningrad, Russia). After graduating from the gymnasium, Lipmann decided to pursue a career in medicine, largely due to the influence of an uncle who was a pediatrician and one of his boyhood heroes. In 1917 he enrolled in the University of Königsberg but had his medical studies interrupted in 1918 as he was called to the medical service during World War I. In 1919, he was discharged from the army and went to study medicine in Munich and Berlin. He eventually returned to Königsberg to complete his studies and obtained his medical degree from Berlin in 1922. Lipmann's interest in biochemistry and physiology was further cultivated when during his practical year of medical studies he worked in the pathology department in a Berlin hospital and took a three-month course in modern biochemistry taught by Peter Rona. Returning to Königsberg, Lipmann, chose to do his thesis work with biochemist Otto Meyerhof, whose physiological investigations focused on the muscle.
For the most part, Lipmann worked on inhibition of glycolysis (the breakdown of glucose by enzymes) by fluoride in muscle contraction and did his doctoral dissertation on metabolic fluoride effects. During this time in Berlin, Lipmann met many of the era's great biochemists, including Karl Lohmann, who discovered adenosine triphosphate (ATP--a compound that provides the chemical energy necessary for a host of chemical reactions in the cell) and taught Lipmann about phosphate ester chemistry, which was to play an important role in Lipmann's later research. During this time Lipmann also met his future wife.
Over the next ten years, Lipmann continued with a varied research career. Lipmann spent a short time in Heidelberg when Meyerhof moved his laboratory there but then returned to Berlin and worked with Albert Fischer on tissue culturing and the study of metabolism as a method to measure cell growth. Soon, uniformed followers of Hitler began to appear in the streets of Berlin; both Lipmann and his wife had unpleasant encounters--and Lipmann was physically assaulted. Realizing that they would soon have to leave Germany, Lipmann, through Fischer's intervention, received an offer to work at the Rockefeller Foundation (now Rockefeller University). At the Rockefeller Foundation, Lipmann worked in the laboratory of chemist Phoebus Aaron Theodor Levene, who had conducted research on the egg yolk protein, which he called vitellinic acid, and found that it contained 10 percent bound phosphate (that is, phosphate strongly attached to other substances). Lipmann's interest in this protein, which served as food for growing animal tissues, led him to isolate serine phosphate from an egg protein.
At the end of the summer of 1932, Lipmann and his wife returned to Europe to work with Fischer, who was now in the Biological Institute of the Carlsberg Foundation in Copenhagen, Denmark. Free to pursue his own scientific interests, Lipmann delved into the mechanism of fermentation and glycolysis and eventually cell energy transformation. In the course of these studies, Lipmann found that pyruvate oxidation (a reaction that involves the loss of electrons) yielded ATP. Lohmann, who first discovered ATP, had also found that creatine phosphate provides the muscle with energy through ATP. Further work led Lipmann to the discovery of acetyl phosphate and the recognition that this phosphate was the intermediate of pyruvate oxidation. A discovery that Lipmann said was his most impressive work and had motivated all his subsequent research.
Before Lipmann could piece together his formula for the foundation of how organisms produce energy, once again the rise of the Nazis forced him to flee to the United States. Lipmann acquired a research fellowship in the biochemistry department of Cornell University Medical College. His work with pyruvate oxidation and ATP had germinated and set him on a series of investigations that led to his theories of phosphate bond energy and energy-rich phosphate bond energy. During a vacation on Lake Iroquois in Vermont, Lipmann began his essay "Metabolic Generation and Utilization of Phosphate Bond Energy," in which Lipmann first proposed the notion of group potential and the role of group transfer in biosynthesis.
Although his essay covered a wide range of topics, including carbamyl phosphate and the synthesis of sulfate esters, Lipmann's explanation of the role of ATP in group activation (such as amino acids in the synthesis of proteins), foretold the use of ATP in the biosynthesis of macromolecules (large molecules). In more general terms, he identified a link between generation of metabolic energy and its utilization. A prime example of ATP's role in energy transmission was the transfer of phosphor potential from ATP to provide the energy needed for muscles to contract.
Subsequently, Lipmann gained an unusual appointment in the Department of Surgery at the Massachusetts General Hospital through the support of a Ciba Foundation fellowship. Building upon his group transfer concept, Lipmann delved into the nature of the metabolically active acetate, which had been postulated as an "active" intermediary in group activation. In 1945, working with a potent enzyme from pigeon liver extract as an assay system for acetyl transfer in animal tissue, Lipmann and colleagues at Massachusetts General Hospital discovered Coenzyme A (CoA), the "A" standing for the activation of acetate. (Coenzymes are organic substances that can attach themselves to and supplement specified proteins to form active enzyme systems.) Eventually, CoA would be shown to occur in all living cells as an essential component in the metabolism of carbohydrates, fats, and certain amino acids. In 1953, Lipmann received the Nobel Prize in physiology or medicine for his discovery specifically of the acetyl-carrying CoA, which is formed as an intermediate in metabolism and active as a coenzyme in biological acetylations. (Lipmann shared the prize with his old colleague and friend, Hans Krebs, from Berlin.) Although proud of the Nobel Prize, Lipmann often stated that he believed his earlier work on the theory of group transfer was more deserving.
In 1957 Lipmann once again found himself at the Rockefeller Institute, twenty-five years after his first appointment there. Lipmann was to spend the next thirty years at the institute, primarily working on the analysis of protein biosynthesis. He and his colleagues contributed greatly to our understanding of the mechanisms of the elongation step of protein synthesis (stepwise addition of single amino acids to the primary protein structure).
In addition to the Nobel Prize, Lipmann received the National Medal of Science in 1966 and was elected a foreign member of the Royal Society in London.
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