Gerty T. Cori

Their studies on glucose use in tumors convinced the Coris that much basic research on carbohydrate metabolism remained to be done. They began this task by examining the rate of absorption of various sugars from the intestine. They also measured levels of several products of sugar metabolism, particularly lactic acid and glycogen. The former compound results when sugar combines with oxygen in the body.

The Coris measured how insulin affects the conversion of sugar into lactic acid and glycogen in both the muscles and liver. From these studies, they proposed a cycle (called the Cori cycle in their honor) that linked glucose with glycogen and lactic acid. Their proposed cycle had four major steps: (1) blood glucose becomes muscle glycogen, (2) muscle glycogen becomes blood lactic acid, (3) blood lactic acid becomes liver glycogen, and (4) liver glycogen becomes blood glucose. Their original proposed cycle has had to be modified in the face of subsequent research, a good deal of which was carried out by the Coris themselves. For example, scientists learned that glucose and lactic acid can be directly inter-converted, without having to be made into glycogen. Nonetheless, the Coris' suggestion generated much excitement among carbohydrate metabolism researchers. As the Coris' work continued, they unraveled more steps of the complex process of carbohydrate metabolism. They found a second intermediate compound, glucose-6-phosphate, that is formed from glucose-1-phosphate. (The two compounds differ in where the phosphate group is attached to the sugar.) They also found the enzyme that accomplishes this conversion, phosphoglucomutase.

By the early 1940s the Coris had a fairly complete picture of carbohydrate metabolism. They knew how glycogen became glucose. Rather than the simple non-enzymatic hydrolysis reaction that, twenty years earlier, had been believed to be responsible, the Coris' studies painted a more elegant, if more complicated picture. Glycogen becomes glucose-1-phosphate through the action of one enzyme (phosphorylase). Glucose-1-phosphate becomes glucose-6-phosphate through the action of another enzyme (phosphoglucomutase). Glucose-6-phosphate becomes glucose, and glucose becomes lactic acid, each step in turn mediated by one specific enzyme. The Coris' work changed the way scientists thought about reactions in the human body, and it suggested that there existed specific, enzyme-driven reactions for many of the biochemical conversions that constitute life.

Resumes Early Interest in Pediatric Medicine

In her later years, Cori turned her attention to a group of inherited childhood diseases known collectively as glycogen storage disorders. She determined the structure of the highly branched glycogen molecule in 1952. Building on her earlier work on glycogen and its biological conversions via enzymes, she found that diseases of glycogen storage fell into two general groups, one involving too much glycogen, the other, abnormal glycogen. She showed that both types of diseases originated in the enzymes that control glycogen metabolism. This work alerted other workers in biomedicine that understanding the structure and roles of enzymes could be critical to understanding diseases. Here again, Cori's studies opened up new fields of study to other scientists. In the course of her later studies, Cori was instrumental in the discovery of a number of other chemical intermediate compounds and enzymes that play key roles in biological processes.