While working in Cori's laboratory, Sutherland, with the help of his co-workers, made several discoveries concerning the mechanism of glycogen metabolism that, years later, led him to his discovery of the biological activity of cyclic AMP. Cori's laboratory had previously established the basic mechanism of glycogen metabolism, for which they were awarded the Nobel Prize in Physiology or Medicine. Sutherland helped to identify the importance of liver phosphorylase (LP) in the process of glycogenolysis. Of the three basic enzymes involved in glycogenolysis, he found that LP was rate-limiting, meaning that the progression of glycogen metabolism is dependent on this enzyme. LP would become the subject of his research for the next several years, and it was through experimentation on LP and hormone interaction that his most renowned discovery was made.