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McCoy et al. 112 (1): 283
J. Biol. Chem., Vol. 277, Issue 37, 25, September 13, 2002
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Classics
The Discovery of the Amino Acid Threonine: the Work of William C. Rose
Feeding Experiments with Mixtures of Highly Purified Amino Acids. I. The
Inadequacy of Diets Containing Nineteen Amino Acids
(Rose, W. C. (1931)
J. Biol. Chem. 94,
155–165)
Feeding Experiments with Mixtures of Highly Purified Amino Acids. VIII.
Isolation and Identification of a New Essential Amino Acid
(McCoy, R. H.,
Meyer, C. E., and Rose, W. C. (1935) J. Biol. Chem.
112, 283–302)
William Cumming Rose (1887–1985) discovered threonine, the last of the 20 amino acids universally present in proteins to be identified. He was born in Greenfield, South Carolina, and at age 16, after schooling at home, entered Davidson College where he majored in chemistry. When Rose started graduate school at Yale, Russell Chittenden was Director of the Sheffield School of Science, which was at that time one of the centers of biochemistry in the United States. During his interview with Chittenden, Rose mentioned nutritional chemistry as an interest and was directed to meet Lafayette B. Mendel, who, with Thomas B. Osborne, was studying the nutritional value of proteins. (Osborne and Mendel are the authors of a previous JBC Classic (1).) Rose's work with Mendel, although not on proteins and amino acids, guided his research throughout his career.
After completing his doctoral studies at Yale, Rose moved to a position as Instructor of Physiological Chemistry at the University of Pennsylvania. During a brief leave in Germany to work with Franz Knoop, he was offered the opportunity to organize a department of biochemistry at the University of Texas College of Medicine in Galveston. There he became professor and head of the department but was persuaded in 1922 to move to the University of Illinois to head the Division of Physiological Chemistry, later Biochemistry, within the Chemistry Department. Until his retirement in 1955, Rose spent the remaining 33 years of his scientific career at Illinois (3).
While interested in many aspects of metabolism, Rose focused his research work on amino acid metabolism and nutrition after arriving at Illinois. Osborne and Mendel had demonstrated nutritional requirements for the individual amino acids (1). The corn protein zein was not adequate as a sole source of nitrogen; tryptophan and lysine were also needed. Rose showed that casein hydrolysate was likewise inadequate as a sole dietary protein; additional histidine was required. It was important that arginine would not replace histidine, which proved incorrect a proposal that histidine and arginine were interchangeable (2). These observations led to efforts to use mixtures of pure, individual amino acids as substitutes for proteins or protein hydrolysates in nutritional studies. The first of this pair of Journal of Biological Chemistry (JBC) Classics reports that 19 pure amino acids did support the growth of rats. Rose and his colleagues had purified 13 of the known amino acids from natural sources, synthesized 6 others, and established the purity of each. Rats lost weight when fed the 19 amino acids as their sole source of dietary nitrogen. Rose concluded that growth-supporting proteins contained at least one additional component that was lacking in the synthetic mixture, or that the proteins provided one or more of the known amino acids in significantly larger quantities. He favored the first explanation.
The second of these JBC Classics identifies the component essential for
growth that was missing from the mixture of 19 amino acids. With growth
stimulation as an assay, Rose and his colleagues used the laborious techniques
available before the development of chromatography to purify the new amino
acid. It was crystallized, and the structure was determined to be
-amino-
-hydroxy-n-butyric acid, later named threonine.
With the addition of threonine to the other 19 amino acids, rats were, for the
first time, successfully reared on a diet in which pure amino acids were the
sole source of nitrogen.
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Over the next 20 years, Rose extended his studies to quantify the dietary requirements for individual amino acids. This quantitative work distinguished the amino acids that are absolutely essential from those that are necessary only for optimal growth. For rats, the omission of histidine, isoleucine, leucine, threonine, lysine, methionine, phenylalanine, tryptophan, or valine resulted in eventual death, whereas omission of arginine resulted in suboptimal growth. Rose went on to determine for each amino acid the minimum daily requirements for optimal growth.
In 1942, Rose and associates turned their attention to the amino acid requirements for humans using basically the same methodology he had with rats except that healthy, male graduate students were the experimental animals. "Subjects" were fed a diet consisting of corn starch, sucrose, butter fat without protein, corn oil, inorganic salts, the known vitamins, and mixtures of highly purified amino acids. The diet included also a large brown "candy," which contained a concentrated liver extract to supply unknown vitamins, sugar, and peppermint oil to provide a "never-to-be-forgotten taste" (3). The adequacy of the diet was assessed, not by survival of the subjects, but by measuring total nitrogen excretion in urine and feces to determine the nitrogen equilibrium. The results proved that only eight amino acids, isoleucine, leucine, tryptophan, lysine, methionine, phenylalanine, threonine, and valine, are required in the human diet. Rose used University of Illinois graduate students for many other studies, and "they were grateful in those days for the free rations, the dollar a day they were paid and the prospect of getting their initials in print in Rose's widely read publications" (3).
As an authority on protein nutrition, Rose was appointed to many panels and boards, including the Food and Nutrition Board of the National Research Council, and was instrumental in advising government agencies on dietary recommendations. He was a dedicated teacher and mentor who inspired many students to follow careers in biochemistry and received many honors for both his research and teaching. Rose served as President of the American Society of Biological Chemists from 1939 to 1941.
On his 90th birthday, former students, colleagues, and friends honored him by establishing the William C. Rose Lectureship in Biochemistry and Nutrition to recognize annually a biochemist who exemplifies Rose's dedication to research training and teaching. The award and lecture were originally given at the University of Illinois to enable Rose to attend. The William C. Rose Award in Biochemistry, as it was later named, is administered by the American Society for Biochemistry and Molecular Biology. The award and lecture are presented each year at the national meeting of the Society.1,2
FOOTNOTES
1 Virtually all of the biographical information was taken from Ref.
3. 
2 We thank Minor J. Coon, Emeritus Professor of Biological Chemistry at the
University of Michigan, for reading this Introduction to the Rose Classic
papers and helpful comments. Professor Coon was a student with Rose.
Additional information about Rose can be found in the JBC Reflection by
Professor Coon (4).
REFERENCES
- JBC Classics: Osborne, T. B., and Mendel, L. B. (1916) J. Biol. Chem. 25, 1–12; (1917) J. Biol. Chem. 31, 149–163 (http://www.jbc.org/cgi/content/full/277/18/e7)
- Rose, W. C., and Cox, G. J. (1926) J. Biol.
Chem. 68,217
–223
[Free Full Text] - Carter, H. E., and Coon, M. J. (1995) Biographical Memoir for William Cumming Rose, Vol.68 , pp. 253–271, National Academy of Sciences, Washington, D. C.
- Coon, M. J. (2002) JBC Reflection: Enzyme ingenuity in
biological oxidations: a trail leading to cytochrome P-450. J.
Biol. Chem. 277,28351
–28363
[Free Full Text]
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