Memories of microbes and metabolism.

As Jackie Gleason was wont to say: "How sweet it really is!" And--reflecting on the 1940s-1980s, when studies of microbial nutrition revealed exciting structure-function relationships of the B-complex vitamins with relevance to metabolism in humans--it really is. A chemistry degree from Beloit College and a doctorate in biochemistry from the University of Wisconsin set the stage for my life's work at Lederle Laboratories, the University of Illinois, and Vanderbilt University. At Lederle my research contributed to folic acid chemistry: coenzyme forms and function; antimetabolites and cancer chemotherapy.

Buthionine sulfoximine, an experimental tool to induce glutathione deficiency: elucidation of glutathione and ascorbate in their role as antioxidants.

The development of buthionine sulfoximine, a selective inhibitor of glutathione biosynthesis, is an important new tool to elucidate the in vivo role of glutathione. Recent investigations have shown that ascorbic acid can serve as an essential antioxidant in the presence of severe glutathione deficiency.

Swainsonine-induced high mountain disease in calves.

Swainsonine, an indolizidine alkaloid in the locoweeds (certain species of the Astragalus and Oxytropis genera), was fed to young Holstein bull calves in their milk at high elevation (3090 m), and the incidence of high mountain disease (HMD) was compared with locoweed-fed and control calves. Five of 5 calves fed swainsonine and 5 of 5 calves fed fresh Oxytropis sericea showed outward signs of HMD, which included edema under the jaws, throat area and brisket and gross and microscopic lesions of HMD and locoweed poisoning. Grossly there were HMD lesions, including congestion of the liver, right ventricular hypertrophy, and dilatation and excessive fluid in the thoracic and abdominal cavities.

Pipecolic acid biosynthesis in Rhizoctonia leguminicola. II. Saccharopine oxidase: a unique flavin enzyme involved in pipecolic acid biosynthesis.

The fungal parasite Rhizoctonia leguminicola produces two indolizidine alkaloids, slaframine and swainsonine, of physiological interest. These alkaloids are biosynthesized from pipecolic acid which in turn is derived from L-lysine in this fungus as shown in the accompanying paper (Wickwire, B.M.