Esmond E. Snell and the B Vitamins
Year: 2005
Type: article
Abstract: The Vitamin Activities of “Pyridoxal” and “Pyridoxamine” (Snell, E. E. (1944) J. Biol. Chem. 154, 313–314) Vitamin B6 and Transamination (Schlenk, F., and Snell, E. E. (1945) J. Biol. Chem. 157, 425–426) A previous Journal of Biological Chemistry (JBC) Classic (1.JBC Classics: Eakin, R. E., Snell, E. E., and Williams, R. J. (1940) J. Biol. Chem. 136, 801–802; Eakin, R. E., Snell, E. E., and Williams, R. J. (1941) J. Biol. Chem. 140, 535–543 (http://www.jbc.org/cgi/content/full/279/41/e5)Google Scholar) on Esmond Emerson Snell (1914–2003) offered a look into Snell's early career, including his Ph.D. studies at the University of Wisconsin (Madison), his postdoctoral work with Roger J. Williams at the University of Texas (Austin), and their research on biotin. This Classic focuses on the later part of Snell's life and his numerous contributions to vitamin B research. After discovering biotin, Snell turned his attention to Streptococcus faecalis R. Unlike other lactic acid bacteria, S. faecalis is unable to grow when supplemented only with a purine base and uracil but grows well when large amounts of thiamine or small amounts of yeast extract are added. Teaming up with Herschel Mitchell, Snell mounted a major effort to purify this new growth factor from spinach. Using a steam kettle and filter press, they processed roughly 4 tons of spinach and came up with a concentrate 130,000 times more active than a standard liver extract at supporting S. faecalis growth (2.Mitchell H.K. Snell E.E. Williams R.J. The concentration of folic acid.J. Am. Chem. Soc. 1941; 63 (2284): 2284Crossref Scopus (128) Google Scholar). They named their new growth factor folic acid, from the Latin word for leaf, folium. Folic acid marked the last of the unidentified bacterial vitamins required by S. faecalis and Lactobacillus casei, and the two bacteria could now be used to assay for substances required for growth. However, when Snell used S. faecalis to assay tissue extracts for pyridoxine (vitamin B6), he noticed that the values he obtained were hundreds to thousands of times higher than those obtained with yeast or animal assays. He reasoned that the extracts contained a substance, which he called he called “pseudopyridoxine,” that the bacteria either responded to in addition to pyridoxine or that enhanced bacterial response to pyridoxine. Snell also found that pseudopyridoxine was elevated in the tissues of animals fed extra pyridoxine as well as in his own urine when he ingested pyridoxine (3.Snell E.E. Guirard B.M. Williams R.J. Occurrence in natural products of a physiologically active metabolite of pyridoxine.J. Biol. Chem. 1942; 143: 519-530Abstract Full Text PDF Google Scholar). He eventually concluded that when he autoclaved the bacterial media, oxidation or amination probably converted pyridoxine to an aldehyde or amine, both of which promoted the growth of the bacteria. Snell enlisted the aid of Karl Folkers at Merck & Co. to synthesize the possible structures for the aldehyde and amine compounds (4.Harris S.A. Heyl D. Folkers K. The structure and synthesis of pyridoxamine and pyridoxal.J. Biol. Chem. 1944; 154: 315-316Abstract Full Text PDF Google Scholar). He tested the compounds for growth-promoting activity in lactic bacteria and determined that the active aldehyde was 2-methyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine (pyridoxal) and that the amine was 2-methyl-3-hydroxy-4-aminomethyl-5-hydroxymethylpyridine (pyridoxamine). The discovery of these two new forms of vitamin B6 is reported in the first JBC Classic reprinted here. Because autoclaving the growth medium increased the activity of pyridoxine, Snell tried the same with pyridoxal and pyridoxamine. He found that with autoclaving pyridoxal activity was greatly reduced in L. casei but was slightly increased in S. faecalis. Because previous experiments had shown that only pyridoxal promoted growth in L. casei, but both pyridoxal and pyridoxamine promoted growth in S. faecalis, the autoclaving result was consistent with the transformation of pyridoxal to pyridoxamine. Snell confirmed this by heating glutamate with pyridoxal and isolating the products. The transamination reaction was fully reversible and corresponded to Reaction 1. Glutamate+pyridoxal⇌pyridoxamine+α−ketoglutarate Reaction 1 Because pyridoxal could also react with other α-amino acids and α-ketoacids including aspartate and oxalacetate, Snell hypothesized that pyridoxal and pyridoxamine should be able to catalyze the following reaction (Reaction 2). Glutamate+oxalacetate⇌α−ketoglutarate+aspartate Reaction 2 In the second JBC Classic, Snell and Fritz Schlenk test tissues from control and vitamin B6-deficient rats for their ability to catalyze the above reaction. They found that tissues from the B6-deficient rats had low transaminase activity. However, when they attempted to increase the transamination rate by adding pyridoxine, pyridoxamine, and pyridoxal, they got variable results. Some experiments showed that the vitamins could catalyze the reaction whereas others showed the opposite. Eventually, Snell would discover that pyridoxal phosphate was the active catalyst and that it also participated in a variety of enzyme-catalyzed reactions involving amino acids. In 1945 Snell returned to Madison as a faculty member at the University of Wisconsin. However, he moved back to Texas in 1951 after being offered a position as Professor of Chemistry with a part-time appointment in the Biochemical Institute. In 1956, he was invited to chair the Department of Biochemistry at University of California Berkeley and served in that role for 6 years. He retired from Berkeley in 1976 and returned to Austin to be chair of the Department of Microbiology. In 1990 Snell retired as an active faculty member but remained a professor emeritus until 2003. During his long and productive career, Snell received numerous awards, including the Meade-Johnson Vitamin B Complex Award in 1946, the Osborne-Mendel Award from the American Institute of Nutrition in 1951, and the William C. Rose Award from the American Society of Biological Chemists in 1985. He was elected to the National Academy of Sciences in 1955 and was elected a Fellow of the American Institute of Nutrition in 1982. He also served as the editor of the Annual Review of Biochemistry from 1968 to 1983. 1All biographical information on Esmond E. Snell was taken from Refs. 5.Miles E.W. Metzler D.E. Esmond Emerson Snell (1914–2003).J. Nutr. 2004; 134: 2907-2910Crossref PubMed Scopus (1) Google Scholar and 6.Snell E.E. From bacterial nutrition to enzyme structure: a personal odyssey.Annu. Rev. Biochem. 1993; 62: 1-27Crossref PubMed Google Scholar.1All biographical information on Esmond E. Snell was taken from Refs. 5.Miles E.W. Metzler D.E. Esmond Emerson Snell (1914–2003).J. Nutr. 2004; 134: 2907-2910Crossref PubMed Scopus (1) Google Scholar and 6.Snell E.E. From bacterial nutrition to enzyme structure: a personal odyssey.Annu. Rev. Biochem. 1993; 62: 1-27Crossref PubMed Google Scholar.
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: W1567378694