The Conversion of Phenylalanine to Tyrosine: the Work of Seymour Kaufman
Year: 2007
Type: article
Abstract: The Nature of the Primary Oxidation Product Formed from Tetrahydropteridines during Phenylalanine HydroxylationJournal of Biological ChemistryVol. 236Issue 3Preview Full-Text PDF Open AccessA NEW COFACTOR REQUIRED FOR THE ENZYMATIC CONVERSION OF PHENYLALANINE TO TYROSINEJournal of Biological ChemistryVol. 230Issue 2Preview Full-Text PDF Open AccessTHE ENZYMATIC CONVERSION OF PHENYLALANINE TO TYROSINEJournal of Biological ChemistryVol. 226Issue 1Preview Full-Text PDF Open Access The Enzymatic Conversion of Phenylalanine to Tyrosine (Kaufman, S. (1957) J. Biol. Chem. 226, 511–524) A New Cofactor Required for the Enzymatic Conversion of Phenylalanine to Tyrosine (Kaufman, S. (1958) J. Biol. Chem. 230, 931–939) The Nature of the Primary Oxidation Product Formed from Tetrahydropteridines during Phenylalanine Hydroxylation (Kaufman, S. (1961) J. Biol. Chem. 236, 804–810) Seymour Kaufman was born in Brooklyn, New York. Having demonstrated some talent in art, he was admitted to the High School of Music and Art in New York. “Ironically, this ability was a significant handicap for my ultimate career in science because it shunted me into a milieu where I was exposed to four years of outstanding daily studio art instruction, but where I took hardly any science courses,” he recalled (1Kaufman S. Experiencing classical enzymology in its prime.Protein Sci. 1996; 5: 1742-1746Crossref PubMed Scopus (0) Google Scholar). “Consequently, on graduation from high school, I knew very little about biology and chemistry.” Fortunately, during his senior year in high school, Kaufman read deKruif's Microbe Hunters and Sinclair Lewis' novel Arrowsmith. These two books made him realize that he wanted to do some kind of biomedical research, either in biochemistry or organic chemistry. He learned that the University of Illinois had an outstanding chemistry department and thus went there for his undergraduate education. He took courses offered by both the organic and biochemistry divisions, but he found that “many of the chemistry courses emphasized what seemed to [him] to be useless facts, e.g. the exact conditions of temperature and pressure under which a synthetic reaction had to be carried out” (1Kaufman S. Experiencing classical enzymology in its prime.Protein Sci. 1996; 5: 1742-1746Crossref PubMed Scopus (0) Google Scholar). The courses were so boring that he began to lose interest in chemistry. This all changed, however, when he took a course on intermediary metabolism by Journal of Biological Chemistry (JBC) Classics author William C. Rose (2JBC Classics: Rose W.C. J. Biol. Chem... 1931; 94 (McCoy, R. H., Meyer, C. E., and Rose, W. C. (1935) J. Biol. Chem.112, 283–302): 155-165http://www.jbc.org/cgi/content/full/277/37/e25Google Scholar) during his senior year. Kaufman also gained valuable experience in synthetic chemistry at this time by working part-time for the Department of Chemistry synthesizing organic compounds that were needed by faculty members for their research. Kaufman received his B.S. degree in 1945 and remained at the University of Illinois to do a Masters degree. He worked with Carl Vesting and published his first paper in the JBC (3Vestling C.S. Kaufman S. Maxwell R.E. Quastler H. The oxidation of octanoate by normal and leucemic mouse liver homogenates.J. Biol. Chem. 1946; 165: 385-386Abstract Full Text PDF PubMed Google Scholar). He graduated in 1946 and went to Duke University to do graduate work with JBC Classics author Hans Neurath (4JBC Classics Schwert G.W. Neurath H. Kaufman S. Snoke J.E. J. Biol. Chem. 1948; 212 (Davie, E. W., and Neurath, H. (1955) J. Biol. Chem. 212, 515–530): 515-530http://www.jbc.org/cgi/content/full/280/2/e1Google Scholar). His time spent working with Neurath firmly consolidated Kaufman's interest in enzymes, which continued throughout his research career. When he graduated 3 years later, he accepted a position as a postdoctoral fellow with JBC Classics author Severo Ochoa (5JBC Classics Stern J.R. Ochoa S. J. Biol. Chem. 1951; 193 (Korkes, S., del Campillo, A., Gunsalus, I. C., and Ochoa, S. (1951) J. Biol. Chem. 193, 721–735): 721-735http://www.jbc.org/cgi/content/full/280/11/e8Abstract Full Text PDF PubMed Google Scholar, 6JBC Classics Salas M. Smith M.A. Stanley Jr., W.M. Wahba A.J. Ochoa S. J. Biol. Chem. 1965; 240: 3988-3995http://www.jbc.org/cgi/content/full/281/21/e16Abstract Full Text PDF PubMed Google Scholar) at New York University Medical School. He worked with Ochoa for 5 years, first as a postdoctoral fellow, then as an Instructor and Assistant Professor. In 1954, Kaufman accepted a position at the National Institute of Mental Health's newly created Laboratory of Cellular Pharmacology. When he arrived in Bethesda, he learned that the new laboratory existed only on paper and that it would be many months until construction was completed. This allowed Kaufman to spend a long time thinking about what his first research project as an independent scientist would be. He wanted a basic problem that, if solved, would help advance the understanding of a clinical problem. He decided to study the enzyme responsible for the conversion of phenylalanine to tyrosine. It had been shown that an inherited inability to convert phenylalanine to tyrosine resulted in the disease phenylketonuria (PKU), so discovering the enzyme(s) involved in the reaction would potentially help to discover appropriate therapies for the disease. In the first JBC Classic reprinted here, Kaufman reports on the partial purification of two enzymes that participate in the conversion of phenylalanine to tyrosine. One enzyme was purified from rat liver, and the other was purified from sheep liver. Kaufman discovered that the reaction also required the presence of triphosphopyridine nucleotide (TPNH; now known as NADPH) and oxygen. In the second Classic, Kaufman reports that in addition to the two enzymes, oxygen, and TPNH, another co-factor was involved in the reaction. Although the identity of the co-factor had yet to be established, it appeared to be different from any other known vitamin or coenzyme. Preliminary studies suggested that the cofactor interacted directly with TPNH. The Classic paper details the purification of the cofactor from rat liver. The new cofactor was eventually identified as a tetrahydropteridine. In the final JBC Classic, Kaufman explores the tetrahydropteridine product formed during phenylalanine hydroxylation. Although no direct evidence had been found for the formation of an oxidized pteridine intermediate, Kaufman had inferred its existence from previous kinetic studies. In the Classic paper, Kaufman reports on conditions in which the intermediate accumulates during the enzymatic conversion of phenylalanine to tyrosine. By synthesizing an active compound which appeared to be identical to the intermediate, he was able to show that it was a double bond tautomer of the inactive 7,8-dihydropteridine. The discovery of this new hydroxylation coenzyme opened up a new field of enzymology, and Kaufman soon became a leading authority on tertrahydrobiopterin. He eventually showed that the missing component in the classical form of PKU is phenylalanine hydroxylase. Several years later, after he had been appointed as the Chief of the Laboratory of Neurochemistry at the National Institute of Mental Health, Kaufman and others described less common forms of the disease and traced them to the lack of other essential components of the hydroxylation system. In recognition of his contributions to science, Kaufman was elected to the National Academy of Sciences and the American Academy of Arts and Sciences in 1987. He received the Hillebrand Prize in 1991. 1Biographical information on Seymour Kaufman was taken from Ref. 1Kaufman S. Experiencing classical enzymology in its prime.Protein Sci. 1996; 5: 1742-1746Crossref PubMed Scopus (0) Google Scholar. 1Biographical information on Seymour Kaufman was taken from Ref. 1Kaufman S. Experiencing classical enzymology in its prime.Protein Sci. 1996; 5: 1742-1746Crossref PubMed Scopus (0) Google Scholar.
Source: Journal of Biological Chemistry
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1497101728