H. Edwin Umbarger's Contributions to the Discovery of Feedback Inhibition
Year: 2005
Type: article
Abstract: Isoleucine and Valine Metabolism in Escherichia coli. V. α-Ketoisovaleric Acid Accumulation (Adelberg, E. A., and Umbarger, H. E. (1953) J. Biol. Chem. 205, 475–482) Harold Edwin Umbarger (1921–1999) was born in Shelby, Ohio. His undergraduate education was at Ohio University, where he graduated in 1943, and his graduate education was at Harvard University, where he received his Ph.D. degree in bacteriology and immunology in 1950. Umbarger also served as a hospital corpsman in the U. S. Navy on the USS Rescue from 1944 to 1946. After completing his graduate studies, he remained in the Department of Bacteriology and Immunology at Harvard Medical School and eventually became Assistant Professor. In 1960 he was appointed Staff Investigator at the Cold Spring Harbor Biological Laboratory and then joined the faculty of Purdue University in 1964. In 1970, he was named Wright Distinguished Professor of Biological Sciences at Purdue. Umbarger was a leading researcher in the field of amino acid biosynthesis in bacteria. However, he is probably best known for his contributions to the discovery of feedback inhibition, which is the subject of the Journal of Biological Chemistry (JBC) Classic reprinted here. Using isoleucineless mutants of Escherichia coli, Umbarger and Edward A. Adelberg showed that the presence of valine in the growth medium inhibited the formation of α-ketoisovalerate, a valine precursor. From this, they concluded that “an end product, in this case valine, can regulate the rate of its own biosynthesis.” The phenomenon of end product inhibition had been demonstrated previously (1Koch A.L. Putnam F.W. Evans E.A. The purine metabolism of Escherichia coli..J. Biol. Chem. 1952; 197: 105-112Abstract Full Text PDF PubMed Google Scholar, 2Abelson P.H. Bolton E.T. Aldous E. Utilization of carbon dioxide in the synthesis of proteins by Escherichia coli..II. J. Biol. Chem. 1952; 198: 173-178Abstract Full Text PDF PubMed Google Scholar, 3Gots J.S. Chu E.C. Studies on purine metabolism in bacteria. I. The role of p-aminobenzoic acid..J. Bacteriol. 1952; 64: 537-546Crossref PubMed Google Scholar), and Umbarger speculated that this was likely a general control phenomenon, although the mechanism was unclear. Three years later, in 1956, Umbarger reported that, in E. coli, isoleucine specifically inhibited the first enzyme-catalyzed reaction in the sequence of steps leading to its biosynthesis from threonine (4Umbarger H.E. Evidence for a negative-feedback mechanism in the biosynthesis of isoleucine..Science. 1956; 123: 848Crossref PubMed Scopus (206) Google Scholar). He stated, “it would seem that the interaction between l-isoleucine and l-threonine dehydrase constitutes a negative-feedback loop that could permit the biosynthesis of isoleucine to proceed only when the level of l-isoleucine in the medium or in the metabolic pool has been reduced to a very low level.” In the same year, Richard Yates and Arthur Pardee reported another example of negative feedback in the inhibition, by cytidine triphosphate, of the first committed step in the pathway leading to its biosynthesis in E. coli. This was the subject of a previous JBC Classic (5JBC Classics Yates R.A. Pardee A.B. J. Biol. Chem. 1956; 221: 757-770Abstract Full Text PDF PubMed Google ScholarGerhart J.C. Pardee A.B. J. Biol. Chem. 1962; 237: 891-896http://www.jbc.org/cgi/content/full/280/41/e38Abstract Full Text PDF PubMed Google Scholar). The discovery of feedback inhibition offered new insights into ways in which the life processes of cells are regulated and opened new approaches to the design of drugs aimed at inhibiting pathogenic organisms. Umbarger was honored for his contributions to science by election to the National Academy of Sciences and the American Academy of Arts and Sciences. He received a Medallion of Pioneering Research from the Ben Gurion University of Negev, Israel, the Rosenstiel Award in Basic Medical Sciences from Brandeis University, and the McCoy Award for Contributions to Science from Purdue. In 1999, Purdue established the Umbarger Distinguished Professorship of Biological Sciences in his honor. Umbarger served as Editor of the Journal of Bacteriology and was on the editorial board of the JBC. He also served as Chairman of the Division of Microbial Physiology of the American Society for Microbiology. Umbarger's coauthor on the paper, Adelberg, also went on to a distinguished career in biochemistry. Several years after the paper was published, he became Chairman of the Department of Bacteriology at the University of California, Berkeley (1957–1961) and then joined the faculty at the Yale University Department of Microbiology, becoming chairman of that department for two terms (1961–1964 and 1970–1972). He was also Director of Biological Sciences at Yale (1964–1969), Deputy Provost for the Biomedical Sciences (1983–1992), and Assistant to the Provost (1993 to present). Currently he is Professor Emeritus in the Yale Department of Genetics. He was elected to the National Academy of Sciences in 1971 and the American Academy of Arts and Sciences in 1979.
Source: Journal of Biological Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1497080620