Tfoe V&wœr . . .
Fritz Lipmann Receives Carl Neuberg Medal A STAFF R E P O R T
JL HE second award of the Carl Neuberg Medal of the American Society of European Chemists and Pharmacists was made to Fritz Lipmann of Massachusetts General Hospital at a meeting of the ASKCP in New York's Master Institute on March 4. Lipmann, head of the biochemical research laboratory of Massachusetts General Hospital and associate in biochemistry at Harvard Medical School, received the award from the hands of the man for whom it» was named and in whose honor it was created, Carl Neuberg, the eminent biochemist. Neuberg Praises Lipmann Neuberg, the first recipient of the medal, which was presented to him at a meeting of the society last November, preceded Lipmann on the program and delivered an address entitled "Fritz Lipmann—The Medalist." A capacity audience heard Neuberg review7 the scientific accomplishments of the medalist which he punctuated with reminiscent references to his personal acquaintanceship with Lipmann and mutual friends in Europe. Neuberg revealed that he firs., made Lipmann's acquaintance in 1927 in Dahlem, Germany, where the latter was working in Meyerhofs laboratory. Lipmann had received his M.D. degree at the age of 23 and had continued his studies toward his Ph.D., which he received under Meyerhof at the age of 28. Shortly after this, Neuberg continued, Lipmann began his investigations into the mechanism of fluoride effects, his first paper showing that under anaerobic conditions no disappearance of lactic acid takes place in muscle tissue in the presence of sodium fluoride. In the next two years, Neuberg explained, it was established that the oxidation quotient of lactic acid is greatly reduced by fluoride, and that in the frog muscle no resynthesis of lactic acid occurs in the presence of fluoride ion. From fluorine mechanisms, Lipmann shifted his interest to those of phosphorus. First with Levene in New York and then later by himself he studied the phosphoric acid linkage in phosphoproteins and determined its position in the hydroxylated amino acids. In particular, Neuberg continued, he isolated serine phosphoric acid, whose product is phosphoglyceric acid, the same substance that plays 860
such a dominant role in carbohydrate metabolism as a primary product of the oxidation step of glycolytic processes. In 1937, Lipmann observed that a transphosphorylation, brought about by cocarboxylase, is essential for pyruvate oxidation. These findings started him, on a series of new investigations, Neuberg continued, in the course of which he developed the ideas of phosphate bond energy and energy rich phosphate bond energy. Although the ordinary ester linkage has a bond energy of 3,000 calories, 11,000 calories are liberated during the hydrolysis of energy rich phosphates. Among the latter, Neuberg declared, are creatinephosphoric acid and adenosine-polyphosphates as well as acylphosphates. Lipmann did much to formulate the laws of metabolic generation and the utilization of the phosphate bond energy. In 1939, Lipmann postulated the occurrence of acetylphosphate, and in 1940 he proved its existence. In 1942, he isolated it and two years later he and his co-workers accomplished the synthesis of the substance and established a method for its determination. Neuberg concluded his address by praising the work of Lipmann on pantothenic acid and his investigations into cancer research and cell structure. Lipmann Discusses Pantothenic Acid After the presentation of the Neuberg medal, Lipmann presented his medalist address in which he discussed the metabolic function of pantothenic acid. He said that of the known water soluble vitamins, thiamin, riboflavin, pyridoxine, and niacin have been shown to exert their physiologic action in the form of phosphorylated derivatives which combine with specific proteins to catalyze certain reactions of intermediary metabolism. The earliest clue to the metabolic role of pantothenic acid, Lipmann explained, came from studies of the oxygen consumption of pantothenic acid deficient cells. The oxidation of pyruvic acid to acetic acid using a purified enzyme system, the medalist said, showed that the oxidation proceeded in two steps in which acetylphosphate was formed in the first and reacted with adenylic acid in the second to form acetic acid and adenosinetriphosphate (ATP). It was possible to reverse C H E M I C A L
Fritz Lipmann 9 head of the biochemical research laboratory of Massachusetts General Hospital this second step of the oxidation, he continued, and it seemed probable that acetylphosphate might be regarded as either a phosphorylat ing or an acetylating agent concerned in biological acetylation. Essential Component of the Coenzyme This thought was reinforced by the successful purification of the coenzyme of pork liver. It was showrn that the same coenzyme which was required for the acetylation of sulfanilamide by the liver enzyme also functioned in the acetylation of choline by the brain enzyme. Acid hydrolysis of the coenzyme, Lipmann continued, and subsequent analysis for ^-alanine indicated that the coenzyme contained about 10% of pantothenic acid. Comparison of the pantothenic acid content and the coenzyme activity of a series of coenzyme preparations of varying potency showed that pantothenic acid was actualh an essential component of the coenzyme. More recent work makes it appear likely, the medalist continued, that the coenzyme is concerned in the reaction of A.TP with acetate leading to the formation of an activated form of the latter, probably phosphorylated, that can then acetylate choline, sulfanilamide, and other substances. It seems unlikely that the function of the coenzyme is limited to that of acetylation, especially in view of its universal presence in cells. The condensation of acetate with sulfanilamide represents the synthesis of a peptide bond whil that of acetate with choline is the formation of an ester linkage. It may be possible, he concluded, that the pantotheniacid-containing coenzyme participates generally in protein and fat syntheses another processes requiring the activation of a, carboxyl group as a preliminary to condensation. A N D
ENGINEERING
NEW
