Since amino acids are the building blocks of protein, they are readily obtained in the process of digesting or degrading protein supplied by foods. But the organism is also capable of synthesizing amino acids from other molecules. For example, bacteria such as E. coli can make the entire basic set of amino acids. Humans can make some of them, which are called " non-essential amino acids," whereas the others that must be supplied in the diet are termed " essential amino acids." When and how many amino acids are to be produced is mainly dependent upon the activity of their biosynthetic enzymes, and the enzymatic activity is often controlled by the final products of the pathway, as seen in the biosynthesis of lysine, threonine, and methionine.

After returning from Europe, Earl resumed his previous research on the metabolism of heterocyclic compounds. This investigation was interrupted in 1963, however, when a postdoctoral fellow, Clifford Woolfolk, joined his laboratory. Although Woolfolk came with a strong desire to follow up Earl's work in Paris on the regulation of aspartokinase, he was advised by Earl to search for another enzyme that could catalyze the first common step in a branched pathway. In 1964, Earl was delighted to find that, among the three candidates Woolfolk suggested, glutamine synthetase was involved in a branched pathway, its activity being regulated by several end products. As Earl later recollected, this "exciting discovery initiated a dramatic change in the focus of much of the research in the Laboratory of Biochemistry and for almost 35 years has occupied the time and energies of numerous highly talented postdoctoral fellows, visiting scientists, and senior associates." It was the beginning of a highly successful, productive research program, in which Earl demonstrated his ingenuity not only as a scientist but also as a leader of many other researchers.

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Glutamine synthetase. Because of its fine control system, this