Pyridine Nucleotide Enzymes and Coenzymes: the Work of Nathan O. Kaplan (2007)

Pyridine Nucleotide Transhydrogenase. III. Animal Tissue Transhydrogenases (Kaplan, N. O., Colowick, S. P., and Neufeld, E. F. (1953) J. Biol. Chem. 205, 1–15) Nathan Oram Kaplan (1917–1986) was born in New York City but moved to Los Angeles when he was 2 years old. Not particularly academically oriented in high school, Kaplan was interested in sports and became a member of the University of California, Los Angeles track team soon after enrolling there as a chemistry major. He planned to become a doctor or to take a job in industry but after graduating in 1939 he decided to go to the University of California, Berkeley for graduate school instead. At Berkeley, Kaplan worked with David Greenberg in the Biochemistry Division of the Berkeley medical school, studying phosphate utilization, distribution, and turnover in various nutritional states in the rat liver. His experience with extracting, separating, and identifying organic phosphate compounds of metabolic significance led to a collaboration with Michael Doudoroff and William Zev Hassid, both of whom were featured in previous Journal of Biological Chemistry (JBC) Classics (1Entner N. Doudoroff M. J. Biol. Chem. 1952; 196 (JBC Classics:): 853-862(http://www.jbc.org/cgi/content/full/280/27/e24)Abstract Full Text PDF PubMed Google Scholar, 2Babad H. Hassid W.Z. J. Biol. Chem. 1964; 239 (JBC Classics:): 946-948Abstract Full Text PDF Google ScholarBabad H. Hassid W.Z. J. Biol. Chem. 1966; 241: 2672-2678(http://www.jbc.org/cgi/content/full/280/34/e31)Abstract Full Text PDF PubMed Google Scholar). Working together, Kaplan, Doudoroff, and Hassid showed that glucose 1-phosphate and fructose were the products of sucrose breakdown. These results were published in the JBC (3Doudoroff M. Kaplan N. Hassid W.Z. Phosphorolysis and synthesis of sucrose with a bacterial preparation.J. Biol. Chem. 1943; 148: 67-75Abstract Full Text PDF Google Scholar); this was Kaplan's first scientific publication. Although his studies were interrupted by his work as a research chemist on the Manhattan Project, Kaplan earned his Ph.D. in 1943. He then spent the next year as an instructor at Wayne State University. In 1945, Kaplan became a research associate with Nobel laureate and JBC Classic author Fritz Lipmann (4Lipmann F. J. Biol. Chem. 1945; 160 (JBC Classics:): 173-190(http://www.jbc.org/cgi/content/full/280/21/e18)Abstract Full Text PDF Google Scholar) at the Massachusetts General Hospital, where he continued his study of liver extracts, focusing on coenzyme A. During his time at Mass General, Kaplan isolated coenzyme A, was instrumental in determining its structure, and helped establish the universality of coenzyme A in 2-carbon metabolism. Kaplan left Lipmann's laboratory in 1949 to become an assistant professor of biochemistry at the University of Illinois College of Medicine. A year later, Kaplan and JBC Classic author Sidney Colowick (5Pullman M.E. San Pietro A. Colowick S.P. J. Biol. Chem. 1954; 206 (JBC Classics:): 129-141(http://www.jbc.org/cgi/content/full/280/39/e36)Abstract Full Text PDF PubMed Google Scholar) left Illinois to become assistant professors at the McCollum-Pratt Institute at Johns Hopkins University. At the Institute, Kaplan and Colowick developed a successful and productive collaboration studying the chemistry of the pyridine nucleotide coenzymes and the enzymes that are involved with them. The JBC Classic reprinted here is just one of the many fruits of this partnership. The work was done in collaboration with Elizabeth Neufeld, who was the subject of a previous JBC Classic (6Barton R.W. Neufeld E.F. J. Biol. Chem. 1971; 246 (JBC Classics:): 7773-7779Abstract Full Text PDF PubMed Google ScholarKresse H. Neufeld E.F. J. Biol. Chem. 1972; 247: 2164-2170Abstract Full Text PDF PubMed Google ScholarCantz M. Chrambach A. Bach G. Neufeld E.F. J. Biol. Chem. 1972; 247: 5456-5462(http://www.jbc.org/cgi/content/full/282/20/e15)Abstract Full Text PDF PubMed Google Scholar). It describes discovery of a transhydrogenase from pig heart mitochondria that transfers hydrogen from TPNH (NADPH) to DPN (NAD) with an equilibrium constant of 1. This was controversial until Martin Klingenberg (7Klingenberg M. Slenczka W. Pyridine nucleotide in liver mitochondria. An analysis of their redox relationships.Biochem. Z. 1959; 331: 486-517PubMed Google Scholar) and Lars Ernster (8Danielson L. Ernster L Demonstration of a mitochondrial energy-dependent pyridine nucleotide transhydrogenase reaction.Biochem. Biophys. Res. Commun. 1963; 10: 91-96Crossref PubMed Scopus (52) Google Scholar) found that the mitochondrial transhydrogenase transfers electrons from NADH to NADP in an energy-dependent reaction. In 2006, Freeman et al. (9Freeman H. Shimomura K. Horner E. Cox R.D. Ashcroft F.M. Nicotinamide nucleotide transhydrogenase: a key role in insulin secretion.Cell Metab. 2006; 3: 35-45Abstract Full Text PDF PubMed Scopus (127) Google Scholar) reported that mice with mutations in the energy-dependent transhydrogenase fail to release insulin from pancreatic beta cells in response to increased glucose levels. Kaplan and Colowick shared a laboratory until 1955 when Kaplan moved out and established his own laboratory in the Institute. However, the pair continued to collaborate on the biochemistry of nucleotides. In addition to their research, Kaplan and Colowick helped to establish a biochemistry division in the Biology Department at the Institute. Their partnership also led to their founding in 1955 of the classic series, Methods in Enzymology. Kaplan remained on the biology faculty of the McCollum-Pratt Institute until 1957, when he became founding chairman of the Graduate Department of Biochemistry at Brandeis University. He played a large role in establishing Brandeis as a major research-oriented university in the sciences in the 1960s. Kaplan remained at Brandeis as Professor and Chairman of Biochemistry until 1968, when he accepted a Professorship in Chemistry at the University of California, San Diego. During the 1970s Kaplan focused his research on chemotherapy and is credited with having discovered the relationship between different types of cancer and the amount of lactate dehydrogenase in the blood. With Gordon Sato, Kaplan founded a nude mouse colony at UCSD's Cancer Center, producing experimental specimens for cancer studies across the country. In 1980, Kaplan became Associate Director of the Cancer Center. Among his honors, Kaplan shared the Sugar Research Award in 1946 for work on phosphorolysis and synthesis of sucrose and the Nutrition Award in 1948 for work on coenzyme A. He was presented the American Chemical Society's Eli Lilly Award in Biological Chemistry in 1953 for work on the metabolic significance of vitamins. Kaplan was elected to the American Academy of Arts and Sciences in 1958 and to the National Academy of Sciences in 1970. He co-edited the journal Analytical Biochemistry and was on the editorial advisory board of several other biochemistry journals including Molecular Pharmacology, Biochemical Genetics, and Biochemical Medicine. 1Biographical information on Nathan O. Kaplan was taken from Ref. 10McElroy W.D. Nathan Oram Kaplan.Vol. 63. National Academy of Sciences, Washington, D. C.1994: 246-292Google Scholar. We thank William S. Allison, Emeritus Professor of Chemistry and Biochemistry at the University of California, San Diego, for providing information for this introduction. 1Biographical information on Nathan O. Kaplan was taken from Ref. 10McElroy W.D. Nathan Oram Kaplan.Vol. 63. National Academy of Sciences, Washington, D. C.1994: 246-292Google Scholar. We thank William S. Allison, Emeritus Professor of Chemistry and Biochemistry at the University of California, San Diego, for providing information for this introduction.