ABSTRACT

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My research on lipoic acid began with its isolation and characterization and then went on to identification of its functional form. The trail then led to elucidation of major features of the structure, function, and regulation of a-keto acid dehydrogenase multienzyme complexes. This trail of discovery started in the spring of 1949, about 6 months after I joined the faculty of the Department of Chemistry at the University of Texas at Austin. At that time I started working on the isolation of a factor that stimulated growth of Lactobacillus casei on an acetate-free synthetic medium. Research on the ‘‘acetate-replacing factor’’ was initiated by Esmond Snell and associates at the University of Wisconsin and then at the University of Texas at Austin. I inherited this project in the spring of 1949. We established that this factor is widely distributed in animal, plant, and microbial cells and that animal liver is a rich source. The factor is tightly bound to liver protein, and it is released by proteolysis or by acid hydrolysis. At that time, pharmaceutical companies were processing large amounts of pork and beef liver to obtain extracts suitable for the treatment of pernicious anemia. The active principle was shown later to be vitamin B12. Fresh liver was extracted with warm water, and the residual liver proteins and fatty material were dried and sold as an animal feed supplement. Arrangements were made with Eli Lilly and Co. to obtain liver residue, and we developed procedures for extracting and purifying the acetate-replacing factor. We were eventually able to process about 6 lb of liver residue at a time. A 16,000-to 50,000-fold purification was achieved.