The Characterization of Intestinal Peptidases by Emil L. Smith
Year: 2004
Type: article
Abstract: The Peptidases of Intestinal Mucosa (Smith, E. L., and Bergmann, M. (1944) J. Biol. Chem. 153, 627-651) Emil L. Smith was born in New York City in 1911. Unlike many other prominent scientists, Smith was not especially interested in science as a child. Says Smith, “It has always intrigued me to learn that so many of my fellow scientists came to their interest in science early in life—because of a gift of a chemistry set or a telescope, or because they observed nature at first hand. I was a late starter and came to science largely by accident and by what, in retrospect, seems a process of drifting first to my interest in science and later to biochemistry” (1Smith E.L. Semenza G. The evolution of a biochemist. Of Oxygen, Fuels, and Living Matter, Part 2. John Wiley & Sons, Ltd., New York1982Google Scholar). 1All of the biographical information for this Classic introduction was taken from Ref. 1Smith E.L. Semenza G. The evolution of a biochemist. Of Oxygen, Fuels, and Living Matter, Part 2. John Wiley & Sons, Ltd., New York1982Google Scholar.1All of the biographical information for this Classic introduction was taken from Ref. 1Smith E.L. Semenza G. The evolution of a biochemist. Of Oxygen, Fuels, and Living Matter, Part 2. John Wiley & Sons, Ltd., New York1982Google Scholar. At age 16, Smith enrolled as a premedical student at Columbia University, because “the required courses in the sciences could lead to another type of career.” Fortunately, Smith's attitude changed during his sophomore year when two gifted teachers stimulated his interest in biology and organic chemistry. After graduating, Smith remained at Columbia to do a Ph.D. on photosynthesis in Selig Hecht's laboratory. By the time he finished his graduate studies in 1936, Smith realized a revolution was happening in biochemistry as more and more physiological phenomena were being attributed to the activity of proteins. Although he had a teaching position as Instructor at Columbia, in 1938 he decided to go to Cambridge University on a Guggenheim Fellowship to work with David Keilin. There he studied the chlorophyll-protein complex until the war forced him to return to the U.S., where he finished his fellowship work with Hubert Bradford Vickery at the Connecticut Agricultural Experiment Station in New Haven. In 1940, he joined Max Bergmann at the Rockefeller Institute. Bergmann had come to the U.S. from Germany because of the rise of Adolph Hitler and the National Socialist government. He had been the Director of the Institut für Lederforschung in Berlin and a student of the prominent German chemist Emil Fischer, who pioneered the study of protein and enzyme chemistry. His laboratory at the Rockefeller provided an opportunity to learn protein and enzyme chemistry without going to Europe, and notable biochemists who worked with Bergmann included Joseph S. Fruton (Yale), William H. Stein (Rockefeller), Stanford Moore (Rockefeller), Carl Nieman (Cal Tech), Klaus Hofmann (Pittsburgh), Heinz Fraenkel-Conrat (University of California, Berkeley), and Paul Zamecnik (Harvard). Bergmann's laboratory was devoted to developing methods of amino acid analysis and the synthesis of synthetic peptides to study proteolytic enzyme specificity. Bergmann suggested that Smith examine the specificity of intestinal erepsin, which is the subject of the Journal of Biological Chemistry (JBC) Classic reprinted here. The motivation behind Bergmann's suggestion was his irritation with a report that the crude enzyme preparation hydrolyzed both l-leucylglycine and d-leucylglycine, which would contradict his “polyaffinity theory.” By purifying what was known as “leucylpeptidase” from the crude intestinal extract, Smith was able to show that the activity toward d-leucylglycine was removed, proving that distinct enzymes cause the splitting of the two stereoisomeric peptides. Smith also found that leucylpeptidase became increasingly responsive to activation by Mn2+ and Mg2+ during the course of purification and that the enzyme displayed equal ability to hydrolyze l-leucylglycine, l-leucylglycylglycine, and l-leucinamide. Because these results indicated that leucylpeptidase was neither a dipeptidase nor a carboxypeptidase but actually an aminoexopeptidase, he renamed it l-leucine-aminoexopeptidase. Smith purified and characterized a variety of other intestinal peptidases, many of which he found also required the addition of metal ions to maintain activity. In 1942 Smith was offered a position at E. R. Squibb and Sons to aid in the development and production of purified human plasma proteins for use by the armed forces. After 4 years of being “knee-deep in blood and other large scale protein fractionations,” Smith left Squibb to head up his own laboratory at the University of Utah, College of Medicine. In 1958 Emanuel Margoliash joined Smith's laboratory and sequenced cytochrome c from several evolutionarily diverse species. Smith and Margoliash found that cytochromes from closely related species showed only a few differences in sequence whereas more distantly related species had a greater number of variant residues. Later Emile Zuckerkandl and Linus Pauling (2Zuckerkandl E. Pauling L. Evolutionarydivergence and convergence in proteins.in: Bryson V. Vogel H.J. Evolving Genes andProteins. Academic Press, New York1965: 97-166Crossref Google Scholar) proposed the idea of the molecular clock based on the sequences of hemoglobin published earlier by others. Smith and Margoliash's cytochrome c sequences (3Margoliash E. Smith E.L. Structural andfunctional aspects of cytochrome c in relation to evolution.in: Bryson V. Vogel H.J. Evolving Genes and Proteins. Academic Press, NewYork1965: 221-242Crossref Google Scholar) supported this idea. Zuckerkandl and Pauling's theory (2Zuckerkandl E. Pauling L. Evolutionarydivergence and convergence in proteins.in: Bryson V. Vogel H.J. Evolving Genes andProteins. Academic Press, New York1965: 97-166Crossref Google Scholar) also proposed that mutations accumulate at an approximately constant rate in DNA as long as the gene retains its original function. Thus, the difference between the DNA sequences of two species should be proportional to the time since the species diverged from a common ancestor. Smith remained in Utah until 1963, when he accepted an appointment as Chairman of the Department of Biological Chemistry at the University of California, School of Medicine in Los Angeles. He eventually terminated his research activities in June 1979 when he was awarded the title of Emeritus. In addition to the above mentioned work, Emil Smith has made numerous other valuable contributions to the field of biochemistry, including determining the sequences of the plant proteinase papain, the subtilisins, and several glutamate dehydrogenases. In 1969, Smith teamed up with James Bonner to sequence cow and pea histone H4. They determined that the two proteins were almost identical, which is the subject of a future JBC Classic. He also spearheaded, in 1954, the writing of the classic textbook Principles of Biochemistry with Abraham White, Philip Handler, and DeWitt Stetten. Smith was recognized for his many scientific achievements with his election to the National Academy of Sciences in 1962.
Source: Journal of Biological Chemistry
Language: English
Subfield: History and Philosophy of Science
Field: Arts and Humanities
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1605637018