Fritz Lipmann

136 TIBS 12- Aprd 1987 Obituaries from egg yolk, contained 10% phos- Fritz Lipmann (1.899-1986): phate by weight Lfpmann speculated ~hat phosvltln might contain a high- an appreciation energy storage form of phosphate (P~N), but he identified it as phosphoserine Fritz lapmann, one of the most influen- tute for Biology (now the Max Planck which was not energy-nch m nature tial biochemists of the 20th century, died Institute) in Berlin Even though When Ltpmann first elucidated the aged 87 on 24 July 1986 in Poughkeepsie. Meyerhof was a Nobel Laureate, he was chemical properties of phosphorylated New York, alter a short illness Since unable to sponsor a PhD student, Carl serme residues in the 1930s, no one could 1969, he had been professor emeritus at Neuberg In Berlin served as Lipmann's predict the importance that they have The Rockefeller University, although he nominal graduate professor After being assumed today Lipmann moved to preferred toomlt 'emeritus' Best known awarded his PhD Lipmann retained Albert Fischer's laboratory at the for introducmg the concept o[ high with Meyerhof's group, where he studied Biological Institute of the Carlsberg energy or energy nch bonds in Foundation in Copenhagen in 1932. and metabolism, which he denoted ~th the remained there until 1939, where he 'squiggle', as in ~P, he was the first scien- stud~ed the Pasteur effect (inhibition of tist to enunciate the pnnclple that ATP glucose consumption by oxygen) in fib- serves as the common currency of energy roblasts m tissue culture Prior to the exchange in metabolism Dr Lipmann advent of antibiotics, this methodology received the Nobel Pnze for Physiology was fraught with difficulty and not as or Medlone in 1953 for the discovery and commonly used as it is today An interest identification of coenzyme A m the Pasteur effect prompted him to the study of the mechanism of pyruvate Early training and sclentdic work oxidation, thereby leading him to the dis- Fritz Lipr~ann was born m covery of acetyl phosphate, an energy- Koenfgsberg, Germany, in 1899 (the city nch and activated form of phosphate (or is now Russian and known as Kahnm- acetate), in Lactobacdlus delbruecku grad) After completing his high school This work served as the background for studies in 1917, he studied medicine in his formulauon of the concept of the high Koenig~berg, Munich and Berlin He energy bond and prompted the line of recalled that his scholastic achievements work which eventually led to the discov- both in school and at the university were ery of coenzyme A only average His medical studies were LIpmann moved to Cornell University interrupted for about a year in 1918when School of Medicine in 1939, where he he served as a military medical assistant worked in Vincent Du Vigneaud's and gained considerable expenence in department in the laboratory of Dean what would now be termed emergency Burk (a former colleague in the medicine Lipmann commented in later Meyerhof laboratory) He compared the years that he was told by a sergeant that phosphate ester chemistry with Karl composition of amino acids with the n- he would never amount to anything His Lohmann The properties of hydrolysis configuration m tumongemc and normal earl) work in biochemistry was done as a of phosphate compounds by 1 ~ HCI tissue and found no difference LIpmann medical student under the tutelage of were important In quantltating and collaborated with Rolhn D Hotchklss at Peter Rona (an early associate of Leonor characterizing ATP, creatme phosphate the nearby Rockefeller Institute to show Michaelts) in Berlin The resulting work and various sugar phosphates OttoWar- that the polypeptlde antibiotics gramlcl- on colloid chemistry was used for his MD burg's group was located at the same din S and tyrocldme contained amino thesis and became the subJect for his first institute, and Hans A Krebs was there acids of the ~configuratlon The first paper, published In Btochenuscbe Zeit- with Warburg at the same tzme volume of Advances in Enzymoiogy shn.~ in 1924 In 192.3 he received a three- Meyerhof accompanied by Lipmann, (1941) ~,,,talned Lipmann's famous month [ellowslup to work with Ernst moved his Institute to Heidelberg in r~vlew m which he discussed the role of Laquer in the Department of Pharmacol- 1930 Lipmann wrote that the time he the high energy bonds of ATP, creatme ogy in Amsterdam It was there that he spent with Meyerhof laid the founda- phosphate and phosphoenolpyruvate in performed his first biochemical research, tions for all that he was to accomplish on metabolism In his autobiography he which prompted him to continue his his own descnbed how he 'stepped into a hor- studies in the biochemical sciences He Dr Lipmann took advantage of a net's nest' by using 'bond energy' to obtained his MD from the University of Rockefeller Foundation fellowship and express the potential energy denvable Berlin in 1924 and pursued a PhD in spent a year with P A Levene at The from a bond instead of the generally Chemistry, which he received Rockefeller Institute for Medical Re- accepted meaning of energy expended to m 1927 under the tutelage of Hans search (now Rockefeller University) in form a bond He also introduced the Meerweln in Koenlgsberg and Otto New York in 1931 Levene had just term 'group transfer potential' in this Meyerhof at the Kaiser-Wilhelm [nsti- demonstrated that phosvltln, isolated article as an alternative to high energy ~1 ILM7Elu.~lcr Puhhcatt~m~ Camhndg~ tFt'lh- ~hT~TP~P2IKI TIBS 12 - Aprd 1987 i 37 bond and group activation In retro- with Krebs, he had already begun look- tyrosme sulfatton m transformed cells spect, the conflicts surrounding the ter- ing toward other problems minology forced everyone to address the In contrast to the redirect routes and Scientific style issues and may have accelerated the blind alleys which finally led to the dis- Llpmann was interested in pnnclples adoption of the concept covery of coenzyme A, the elucidation of of life's processes and worked with the the nature of actwe carbamate as car- most appropnate systems to address Later scientific work bamoyl phosphate in 1955 came in a very specific questions He tned to idenufy Lipmann took a position as a direct and straightforward fashion important problems and work toward Research Chemist tn the Department of In 1957 Dr Lipmann moved to The their solution Some research inevitably Surgery at the Massachusetts General Rockefeller University as professor led into blind alleys and many results Hospital in Boston m 1941 Up untd this where he worked on vanous aspects of were not of great importance He pre- time he had done most of his own expen- nbosomal protein synthesis for 15 years ferred, moreover, to work in areas which mental work vath some collaboration, He was greatly interested m the were not overcrowded with other mvesU- moreover, he was the sole author on 35 mechanism of amino acid activation by gators After the discovery of coenzyme of the 47 full papers he had then pub- adenylatlon and the subsequent forma- A, for example, he left the field to let lashed In 1941, he supervised his first tion of charged transfer RNA This others do the "mopping up' He minuted full-time technician (L Constance Tut- mechamsnt with the involvement of the work on cyclic AMP in the late 1960s, tie), who was to be co-author on several pyroph,~sphate split, parallels acetate soon thought that this area was becom- subsequent pubhcattons Dunng 1942- and fatty acid actwatnon and this may ing overcrowded, and subsequently 1943 he was joined by H A Barker, have been part of the basis for his attrac- devoted much less of his energy to this who was on sabbatical leave from the tion toward this problem The resolution research Umverslty of Cahfomm This oegan the of bacterial elongation factors into Tu One of h,s favonte expressions was era of the discovery of active acetate as a and Ts (unstable and stable) and G was "What is the mechanism 'y' He mapped denvatlve of coenzyme A (coenzyme of a formidable problem The properties out general areas of research and direc- acetylauon), resulting m our present and mechanisms associated with the tions In later years he rarely des,gned a awareness that coenzyme A plays a cen- elongation factors also attracted his protocol, and left this task to the mem- tral role in the metabolism of all attention Francois Chapevllle, working bers of his laboratory When progress organisms m Ltpmann's laboratory, prepared was being made, he wanted to be kept The number of students and postdoc- [14Clalamne-tRNAC- by reduction of informed and continued to be excited toral fellows assocmted with Ltpmann [t4C]cysteine-tRNAC- In collaborative and stimulated by the results When a increased greatly dunng this work expenments w~th Seymour Benzer, it project was not going well, he freely Nathan O Kaplan was the first postdoc- was demonstrated that the alanyl denva- offered his suggestions for trying new toral associate to joan him and G David tire was incorporated into hemoglobin in approaches It was generally up to post- Novelh was his first graduate student postt|ons corresponding to cysteme This doctoral associates or graduate students Earl R Stadtman, a graduate student proved that the adaptor RNA was the to write the papers He might make a few with H A Barker, soon joined the lab- important component in the placement changes, or he might completely re-write oratory as a postdoctoral fellow Other of amino acids in the polypeptide chain the manuscript He spent considerable laboratories played an important role and not the amino acid perse time writing reviews on ,ubjects of his m work on the coenzyme A.

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