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How did scientists discover that proteins are continually synthesized and degraded in cells?

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Diagram showing how epinephrine binding to a beta-adrenergic receptor on a cell membrane activates a G-protein, which then stimulates adenylyl cyclase to convert ATP into cyclic AMP (cAMP), leading to physiological effects such as increased heart rate, blood vessel dilation, and glycogen breakdown. — Biochemistry In biochemistry, researchers study the chemical substances and processes that occur in living organisms and cells. In particular, various processes by which cells gain energy, such as epinephrine-stimulated cAMP synthesis, have been deduced through the study of biochemistry.

Scientists discovered that proteins are continually synthesized and degraded in cells by using isotopes to trace the fate of nutrients within an organism.1

Prior to this discovery in the 1930s, it was widely believed that tissue proteins were stable structures that remained unchanged until the death of the cell. This view was overturned when researchers, notably Rudolf Schoenheimer and his colleagues, fed animals amino acids labeled with isotopic nitrogen.12

Even though the total protein content of the liver and gut tissues remained constant, the researchers found that the labeled isotopes were rapidly incorporated into the proteins of those tissues. This evidence revealed that proteins exist in a dynamic steady state, where high rates of synthesis are balanced by equal rates of degradation. This turnover process allows cells to adjust to changes in their environment, though the rate of this "dynamic state" varies significantly between different tissues, such as the liver versus the muscle or brain.1