Meyerhof, Otto Fritz (1884-1951)

German-born US biochemist who carried out research into the metabolic processes involved in the action of muscles. For this work he shared the 1922 Nobel Prize for Physiology or Medicine.

Meyerhof was born in Hanover and studied at a number of German universities. From 1912 he worked at the University of Kiel, becoming professor 1918. He headed a department specially created for him at the Kaiser Wilhelm Institute for Biology in Berlin 1924-29, when he moved to Heidelberg. As a result of Adolf Hitler's rise to power in the 1930s, Meyerhof left Germany 1938 and went to Paris, where he became director of research at the Institut de Biologie Physiochimique. In 1940, when France fell to Germany in the early part of World War II, he fled to the USA, and was given a professorship at the University of Pennsylvania. In 1920 Meyerhof showed that, in anaerobic conditions, the amounts of glycogen metabolized and of lactic acid produced in a contracting muscle are proportional to the tension in the muscle. He also demonstrated that 20-25% of the lactic acid is oxidized during the muscle's recovery period and that energy produced by this oxidation is used to convert the remainder of the lactic acid back to glycogen. Meyerhof introduced the term glycolysis to describe the anaerobic degradation of glycogen to lactic acid, and showed the cyclic nature of energy transformations in living cells. The complete metabolic pathway of glycolysis is known as the Embden-Meyerhof pathway after Meyerhof and Gustav George Embden (1874-1933). The Beginning of Meyerhof's Career in Science in detail

Ludolf von Krehl was building up a small research program on metabolism at his University of Heidelberg Medical Clinic at the same time that Otto Meyerhof was finishing up his medical studies in Heidelberg. Otto Warburg, who had been a student of Emil Fischer, had joined Krehl in 1906. When Krehl offered Meyerhof his first research position in 1909, it was Warburg's responsibility to teach the newly graduated physician his techniques for investigations of respiration, oxygen consumption and growth rates in sea urchin eggs. Warburg's innovative ideas and dynamic, self-confident approach had a dramatic impact on Meyerhof, inspiring him to focus his career on physiological chemistry. Meyerhof worked at Krehl's laboratory for little over two years, but the establishment of ties with Krehl and the development of his close friendship with Warburg were to be factors which would continue to shape Meyerhof's career.

After leaving Heidelberg, Meyerhof took a position at the University of Kiel, where he quickly began to make a name for himself. In 1913, he presented an epoch making lecture on the energetics of living cells. This was one of the very first adaptations of the physical laws of thermodynamics to physiological chemistry. Meyerhof's goal was to understand how energy is transformed during chemical interactions in the cell. He recognized that between initial energy input via food and its final dissipation as heat, a series of intermediate steps to transform that energy must occur to maintain the organism in a state of dynamic equilibrium. With minor revisions, his theory on the thermodynamics of living matter remained influential for decades.

In his ensuing efforts to relate energy transformations and chemical changes to cellular function, Meyerhof turned his attention increasingly toward experimentation with muscle, where such transformations promised to be large enough in scale to test his new theory. Meyerhof, however, was also interested in analogies between oxygen respiration in muscle and alcoholic fermentation in yeast and the role that enzymes played in both. 1918 marked the first experimental milestone in Meyerhof's career, when he showed that a coenzyme involved in the production of lactic acid in muscle was the same as Harden and Young's coenzyme in alcoholic fermentation in yeast. This was important early evidence of the unity in life of fundamental biological processes.

In his 1913 address, Meyerhof had mentioned the work of the Englishman, A.V. Hill. Hill had pioneered methods to measure heat production in biological processes. Since Meyerhof's lecture, Hill had found a pattern of discrete temperature changes during muscle contraction and relaxation that suggested a complicated series of biochemical interactions. This reminded him of work by Fletcher and Hopkins in 1907, which had shown that lactic acid increases in resting muscle in an oxygen-free environment, but then disappears when oxygen is reintroduced. Hill noted that his own measurements of heat during anaerobic conditions correlated strikingly to Fletcher's and Hopkins' results. This was important evidence for the theory that lactic acid was not simply a by-product of muscle activity, but must be a part of the muscle machine itself.

Soon after the end of World War One, Meyerhof began collaborating with A.V. Hill. Both men were convinced that a key to understanding metabolism lies in quantitatively correlating data on heat development, mechanical work and cellular chemical reactions. In Germany, Meyerhof focused on chemical methods to measure oxygen consumption, the conversion of carbohydrates, lactic acid formation and decomposition, then correlating it to thermodynamic data and various phases of muscle activity. Meyerhof at the the time of the award of his Nobel Prize Between 1918 and 1922, Meyerhof worked out an extraordinary amount of this biochemical detail, including proofs that it is glycogen that is converted into lactic acid in the absence of oxygen. He also showed that in the presence of oxygen, only one-fifth to one-fourth of lactic acid production during anaerobic contraction of the muscle is subsequently oxidized to carbon dioxide and water. Thus, Meyerhof tied the release of energy during this particular oxidation to the reconversion of the remaining four fifths of the lactic acid back to glycogen.

These results had several important ramifications: they explained the course of heat production measured by Hill; and they confirmed and extended a famous theory of Pasteur's that less glycogen is consumed in muscle metabolism in the presence of oxygen than in its absence. The depression of glycolysis by respiration was thereafter referred to as the Pasteur-Meyerhof effect. This would be significant later on in working out the full details of the glycolytic pathway. Finally and most importantly, the conversion of glycogen to lactic acid and back again to glycogen was the first evidence of the cyclical character of energy transformations in living cells. Meyerhof called it the lactic acid cycle. Meyerhof and Hill's analysis of this cycle and its relation to respiration earned both men the Nobel Prize in 1922.

Meyerhof and A.V. Hill, with whom he won the Nobel Prize, at the KWImF around 1931.
Standing in the background from left to right are Karl Lohmann, Alexander von Muralt,
Grigore Alexandru Benetato, Hermann Blaschko, Arthur Grollman,
H. Laser, his technicians Fischer and Schulz and Eric Boyland.

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