Selenoproteins—Tracing the Role of a Trace Element in Protein Function

I n retrospect, the history of selenium biochemistry does not differ greatly from the study of a number of other trace elements in that it occurred over many years, progressing from periods of little general interest to widespread concern regarding toxicity problems and eventually to recognition of selenium as an essential nutrient for many forms of life. My involvement in studies on selenium metabolism is a classic example of serendipity. I was studying an interesting enzyme from an anaerobic bacterium that utilized glycine as substrate (glycine reductase), but the amounts of pure protein I could isolate were very limited because it seemed to be produced only during the very early stages of bacterial cell growth. The rich culture medium supported continued luxuriant growth of the bacterium, but the level of the desired enzyme in the cells merely underwent dilution during the process. Finally, after testing many known growth stimulatory supplements to no avail, my colleagues and I tried two inorganic nutrients, molybdate and selenite. This approach was prompted by the report that addition of these inorganic compounds to a medium used for anaerobic growth of Escherichia coli supported synthesis of the enzyme formate dehydrogenase [1]. Much to my delight, addition of selenite to our growth medium resulted in greatly increased levels of the glycine reductase enzyme, and synthesis of the protein continued throughout the entire growth period. Thus, a common belief among microbiologists that a so-called rich culture medium high in tryptone and yeast extract content was nutritionally adequate is incorrect if growth of the organism depends on ability to synthesize a selenium-containing enzyme. In our case other amino acids in the medium could support growth even when the trace of selenium was depleted and synthesis of glycine reductase stopped. With this unexpected fi nding, we had an ideal biological system for unraveling details of the role of selenium in the anaerobic metabolism of glycine. The element selenium was discovered by the Swedish chemist Berzelius in 1817, and the few organic selenium-containing compounds that were prepared during the subsequent 100 years were considered primarily as chemical curiosities. Finally, in the 1930s, selenium was recognized as the potent toxic substance present in various types of plants that, when ingested by grazing animals, caused chronic symptoms of poisoning. Determination of the selenium contents of several native plants from Wyoming and South Dakota revealed that members of the genus Astragalus accumulated extremely high …