Lester J. Reed and the α-Keto Acid Dehydrogenase Complexes

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α-Keto Acid Dehydrogenation Complexes. IV. Resolution and Reconstitution of the Escherichia coli Pyruvate Dehydrogenation Complex (Koike, M., Reed, L. J., and Carroll, W. R. (1963) J. Biol. Chem. 238, 30–39) Lester James Reed was born in 1925 in New Orleans, Louisiana. He received his B.S. degree from Tulane University in 1943 and completed his Ph.D. in organic chemistry with Reynold C. Fuson at the University of Illinois, Urbana in 1946. He then took a position as a postdoctoral research associate at Cornell University Medical College with Vincent du Vigneaud, who was featured in a previous Journal of Biological Chemistry (JBC) Classic (1JBC Classics: du Vigneaud, V., Cohn, M., Chandler, J. P., Schenck, J. R., and Simmonds, S. (1941) J. Biol. Chem.140, 625–641; du Vigneaud, V., Melville, D. B., Folkers, K., Wolf, D. E., Mozingo, R., Keresztesy, J. C., and Harris, S. A. (1942) J. Biol. Chem.146, 475–485; du Vigneaud, V., Ressler, C., and Trippett, S. (1953) J. Biol. Chem.205, 949–957; Katsoyannis, P. G., and du Vigneaud, V. (1958) J. Biol. Chem.233, 1352–1354 (http://www.jbc.org/cgi/content/full/279/51/e11)Google Scholar). In 1948, Reed joined the faculty of the Department of Chemistry at the University of Texas at Austin, where he became Professor in 1958, Director of the Clayton Foundation Biochemical Institute in 1963, and Ashbel Smith Professor in 1984. He retired in 1999 and is currently Ashbel Smith Professor Emeritus. About 6 months after Reed joined the faculty of the University of Texas he started working on the isolation of a factor that replaced acetate in the growth medium for certain lactic acid bacteria. The project was inherited from Esmond Snell, a JBC Classic author (2JBC 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, 3JBC Classics: Snell, E. E. (1944) J. Biol. Chem.154, 313–314; Schlenk, F., and Snell, E. E. (1945) J. Biol. Chem.157, 425–426 (http://www.jbc.org/cgi/content/full/280/13/e10)Google Scholar) who had initiated the studies while at the University of Wisconsin and continued them after he moved to Texas. Reed eventually purified this acetate-replacing factor and named it α-lipoic acid (4Reed L.J. DeBusk B.G. Gunsalus I.C. Hornberger Jr., C.S. Crystalline α-lipoic acid: a catalytic agent associated with pyruvate dehydrogenase.Science. 1951; 114: 93-94Crossref PubMed Scopus (232) Google Scholar). Intrigued by this compound, he started to investigate its biological function. He determined that protein-bound lipoic acid was involved in the CoA- and NAD+-linked oxidative decarboxylation of pyruvate and α-ketoglutarate. This discovery led Reed to studies on the α-keto acid dehydrogenase complexes, which is the subject of the JBC Classic reprinted here. At that time, enzyme complexes that catalyzed the oxidative decarboxylation of pyruvate and α-ketoglutarate had been isolated from both pig heart and Escherichia coli, and it was believed that as many as four separate enzymes were involved in the reactions. Reed developed a mild procedure for purification of the pyruvate and α-ketoglutarate oxidation systems from E. coli, and by the late 1950s Masahiko Koike in his laboratory succeeded in isolating the enzyme systems as highly purified functional units. Over a period of several years, Reed, Koike, and William Carroll dissected the pyruvate and α-ketoglutarate dehydrogenase complexes into their component enzymes, characterized them, and reassembled the large functional units from the isolated enzymes. Reed’s Classic paper describes the separation of the E. coli pyruvate dehydrogenase complex into three components: (a) pyruvic carboxylase, (b) a component containing bound lipoic acid and exhibiting dihydrolipoic transacetylase activity (the lipoic reductase-transacetylase), and (c) a flavoprotein, dihydrolipoic dehydrogenase. These later became known as the E1 (pyruvate dehydrogenase), E2 (dihydrolipoyl transacetylase), and E3 (dihydrolipoyl dehydrogenase) enzymes, multiple copies of which make up the pyruvate dehydrogenase complex. After publishing this Classic, Reed continued to study the structure and function of the pyruvate and α-ketoglutarate dehydrogenase complexes and their individual components from both mammals and bacteria. Details of this subsequent research can be found in Reed’s JBC Reflections (5Reed L.J. A trail of research from lipoic acid to α-keto acid dehydrogenase complexes.J. Biol. Chem. 2001; 276: 38329-38336Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar). Reed has served on the editorial boards of the Archives of Biochemistry and Biophysics, the Journal of Biological Chemistry, and Biofactors. His honors and awards include the American Chemical Society's Eli Lilly Award in Biological Chemistry (1958), an Honorary Doctor of Science Degree from Tulane University (1977), and the American Society for Biochemistry and Molecular Biology's Merck Award (1994). Reed was elected to the National Academy of Sciences in 1973 and the American Academy of Arts and Sciences in 1981. His family and friends established the Lester B. Reed Professorship in Biochemistry in his honor.