Carbamyl Phosphate Biosynthesis: the Work of Mary Ellen Jones
Year: 2007
Type: article
Abstract: The Pathway of Carbonate in the Biosynthesis of Carbamyl Phosphate (Jones, M. E., and Spector, L. (1960) J. Biol. Chem. 235, 2897–2901) Initial Steps in Pyrimidine Synthesis in Ehrlich Ascites Carcinoma in Vitro. II. The Synthesis of Carbamyl Phosphate by a Soluble, Glutamine-dependent Carbamyl Phosphate Synthetase (Hager, S. E., and Jones, M. E. (1967) J. Biol. Chem. 242, 5667–5673) Mary Ellen Jones (1922–1996) was born in La Grange, Illinois. She became interested in biology when she was in high school, and as a result she majored in biochemistry at the University of Chicago. She earned her B.S. in 1944. During her time at the University of Chicago, Jones was also employed part time as a bacteriologist at Armour and Company. After graduating, she worked at Armour for 4 more years and was eventually promoted to research chemist. Her work at the company resulted in her first two scientific publications (1Munson P.L. Jones M.E. McCall P.J. Gallagher T.F. A colorimetric method for estimation of dehydroisoandrosterone and its application to urine extracts. J. Biol. Chem. 1948; 176: 73-82Google Scholar, 2Jones M.E. Koch F.C. Heath A.E. Munson P.L. Isolation of α-monopalmitin from hog pancreas. J. Biol. Chem. 1949; 181: 755-760Abstract Full Text PDF PubMed Google Scholar), both in the Journal of Biological Chemistry (JBC). Jones entered the Yale University graduate program in 1948 and earned her Ph.D. in 1951. She did her thesis research on the catalytic properties of cathepsin C under the direction of Joseph Fruton. Jones then did a postdoctoral fellowship with JBC Classic author Fritz Lipmann (3Lipmann F. JBC Classics. 1945; 160 (http://www.jbc.org/cgi/content/full/280/21/e18): 173-190Abstract Full Text PDF Google Scholar) in the Chemical Research Laboratory at Massachusetts General Hospital. It was during her time with Lipmann that Jones, along with Leonard Spector, discovered carbamyl phosphate (4Jones M.E. Spector L. Lipmann F. Carbamyl phosphate, the carbamyl donor in enzymatic citrulline synthesis. J. Am. Chem. Soc. 1955; 77: 819-820Google Scholar), a compound essential for the biosynthesis of arginine, urea, and pyrimidine nucleotides. Jones and Lipmann also showed that in microorganisms, carbamyl phosphate is formed when the terminal phosphate of ATP is transferred to carbamate (5Jones M.E. Lipmann F. Chemical and enzymatic synthesis of carbamyl phosphate. Proc. Natl. Acad. Sci. U. S. A. 1960; 46: 1194-1205Crossref PubMed Google Scholar). Jones remained at Massachusetts General Hospital until 1957 after which she became an assistant professor in the newly established graduate Department of Biochemistry at Brandeis University. She was promoted to associate professor in 1960. At Brandeis, Jones continued her work on carbamyl phosphate in collaboration with Spector. As reported in the first JBC Classic reprinted here, they established that carbon dioxide or bicarbonate is the source for the initial activation step leading to carbamyl phosphate formation by carbamyl-phosphate synthetase in animal tissues. Using H 182O, and KHC18O3, they showed that oxygen was added to the orthophosphate residue of carbamyl phosphate via equilibration of water with bicarbonate. Several years later, Jones speculated that there were two separate carbamyl-phosphate synthetase isozymes: one that required ammonia for the synthesis of arginine or urea and one dependent on glutamine for the synthesis of orotate. In 1966, Jones and Sally E. Hager isolated the glutamine-dependent carbamyl-phosphate synthetase from the rat liver. Their paper, published in Science (6Jones M.E. Hager S.E. Source of carbamyl phosphate for pyrimidine biosynthesis in mouse Ehrlich ascites cells and rat liver. Science. 1966; 154: 422Google Scholar), was the first to demonstrate the existence of carbamyl-phosphate synthetase II. They followed the Science paper with a detailed description of their isolation procedure in the JBC. This article is the second JBC Classic reprinted here. In attempting to isolate carbamyl-phosphate synthetase II, Jones and Hagar realized that the enzyme was extremely unstable, which explained why it had not been isolated before. However, by adding the substrate ATP to the homogenization buffer, they were able to stabilize the enzyme and purify and characterize it. They showed that carbamyl-phosphate synthetase II had a high affinity for glutamine but demonstrated low activity with ammonia. Jones later determined that carbamyl-phosphate synthetase I is found in mitochondria and preferentially uses ammonia in the formation of citrulline by ornithine carbamyltransferase, and carbamyl-phosphate synthetase II occurs in the cytoplasm and only uses glutamine for the formation of carbamyl-aspartate by the enzyme aspartate carbamyltransferase. Bacteria, on the other hand, only had one carbamyl-phosphate synthetase whose product, carbamyl phosphate, was used for either arginine or for pyrimidine synthesis. In 1966, Jones joined the University of North Carolina at Chapel Hill as an associate professor of biochemistry. She was promoted to professor 2 years later, and in 1968 was appointed professor in the Department of Zoology. Jones left Chapel Hill in 1971 for the University of Southern California School of Medicine where she was a professor of biochemistry until 1978. Then, she returned to the University of North Carolina to chair the Department of Biochemistry. She was named a Kenan Professor in 1980 and continued active research until 1995. Jones was the first woman scientist to hold an endowed chair at the University of North Carolina and the first woman to become a department chair at the medical school. Jones was widely recognized for her scientific accomplishments and for her leadership roles. Among her awards were the Wilbur Lucius Cross Medal from Yale University (1982), the North Carolina American Chemical Society Distinguished Chemist Award (1986), the Thomas Jefferson Award from the University of North Carolina (1990), and the state of North Carolina's Award in Science (1991). She was elected to the Institute of Medicine (1981), the National Academy of Sciences (1984), the American Association of Arts and Sciences (1991), and the American Philosophical Society (1994). Jones was president of the Association of Medical School Departments of Biochemistry in 1985, the American Society for Biochemistry and Molecular Biology in 1986, and the American Association of University Professors in 1988. She was also honored by having a research center dedicated with her name at the University of North Carolina. 1Biographical information on Mary Ellen Jones was taken from Ref. 7Traut T.W. Biographical Memoir of Mary Ellen Jones. 2001; 79 (National Academy of Sciences, Washington, D. C.): 182-202Google Scholar. 1Biographical information on Mary Ellen Jones was taken from Ref. 7Traut T.W. Biographical Memoir of Mary Ellen Jones. 2001; 79 (National Academy of Sciences, Washington, D. C.): 182-202Google Scholar.
Source: Journal of Biological Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1557882829