Understanding how the human body processes sugars, particularly glucose, is fundamental to our knowledge of human health and disease. The supply of glucose can vary greatly based on diet or time of day. However, the levels of glucose in the bloodstream must remain fairly constant in order to maintain a steady energy supply and prevent damage to various organs. To do this, the human body has an intricate system of checks and balances to regulate how much glucose is allocated to storage versus allowed to enter the bloodstream. The scientist featured in today’s article was instrumental in discovering how this system functions. In 1947, Gerty Theresa Cori was awarded the Nobel Prize in Physiology or Medicine “for [her] discovery of the course of the catalytic conversion of glycogen.” She was the first woman to receive this award, and the third woman to receive a Nobel Prize. She shared the prize with Carl Cori, her husband and collaborator for decades, and Bernardo Houssay, a sugar metabolism researcher from Argentina.
Life and Career
Gerty met her husband while they were both attending medical school in Prague at the beginning of World War I. After being separated when Carl was drafted into the Austrian army, they married in 1920 and worked as both physicians and researchers in Vienna. Gerty remained in Vienna until she was able to obtain a position at the State Institute for the Study of Malignant Disease in Buffalo, where Carl had secured a position in 1922. Gerty and Carl collaborated extensively for the rest of their research careers, eventually moving to Washington University of St. Louis in 1931, where they worked together until Gerty’s death in 1957. As a female scientist working in the early 20th century, Gerty faced a fair degree of gender discrimination. For example, when they started at Washington University, Gerty was paid only one tenth of what Carl was paid, despite having similar education and research experience. The Coris also faced resistance to collaborating in their research, as many scientists thought it strange, counter-productive, and even un-American for a husband and wife to be working together. However, Gerty did not allow the opinions of her colleagues to hamper her research. Far from riding on her husband’s coattails, Gerty worked tirelessly to earn every honor she received, eventually being promoted to professor at Washington University. She was an equal partner in every collaboration with Carl and conducted large amounts of her own research. Though not always treated as such, Gerty eventually proved that she was a great biochemist, both to her colleagues, to those she mentored, and to the Nobel Prize committee.
Before the Cori’s research into the biochemistry of glucose metabolism began, it was known that defects in glucose metabolism cause diabetes and that administration of the hormone insulin can keep diabetes in check. It was also known that glucose is stored in the liver and muscle as glycogen, which is a polymer, or long chain, of glucose molecules analogous to starch in plants. What was not known was exactly how levels of glucose and glycogen are maintained or the mechanisms of conversion between glucose and glycogen. This is where the Coris stepped in.
Glucose shuttle: The Cori Cycle
While not the research that earned her the Nobel Prize, the proposal and the demonstration of the Cori cycle is still a fundamental part of Gerty’s contribution to this field. The cycle that the Coris proposed begins in skeletal muscle, where glucose is made from stored glycogen and utilized to produce the large amounts of energy that muscles need to function. If oxygen supplies in the muscle are low, as often happens during exercise, a byproduct of the reactions that harvest energy from glucose is lactic acid. This lactic acid is shuttled to the liver via the bloodstream, where it is converted back to glucose through a long, multistep process known as gluconeogenesis. This newly re-formed glucose is either used to make more liver glycogen or sent via the bloodstream back to the skeletal muscle, where it is used to replenish glycogen stores. In this way, the function of the liver as an energy storehouse and the function of the muscle as an energy producer are coordinated to help meet the demands of daily life as a human. Gerty, working closely with her husband, helped to theorize and later prove the existence of this cycle. They also discovered that insulin increases the synthesis of glycogen in both the liver and muscle, while another hormone known as adrenaline or epinephrine decreases muscle and liver glycogen stores. These discoveries increased our knowledge of how sugar metabolism works in general, which helped us to understand the negative effects of diabetes and many other metabolic diseases.
Glycogen breakdown: The Cori Ester
The other fundamental discovery made by Gerty and her husband was the first product of glycogen breakdown. This product is similar in structure and size to glucose, but with a phosphate group (a large, negatively charged structure) attached. This phosphate group and its position on the molecule allow the proteins involved in glycogen metabolism to recognize it and shuttle it to the next step in making a form of glucose the body can use for energy. The Coris were able to discover this molecule, which they named glucose-1-phosphate, from preparations of frog skeletal muscle, which they used extensively in their biochemical research. The Coris also established the structure of this molecule and the enzyme that produces it, which they named phosphorylase. The discoveries of glucose-1-phospate (also termed the Cori esther) and phosphorylase was one of the first steps toward understanding the intricate regulation of glucose metabolism, an understanding which is taken for granted by biochemistry students today. The discovery was honored when the US Postal Service included Gerty on a stamp in April of 2008, despite a small error in the structure. Her greatest honor, despite having two craters named after her and her husband, was to have her name attached to two such fundamental aspects of glucose metabolism.
Stamp honoring Gerty Cori. From the Washington University Magazine.
Sources and further reading
- American Chemical Society National Historic Chemical Landmarks. Carl and Gerty Cori and Carbohydrate Metabolism. http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/carbohydratemetabolism.html (accessed April 4, 2015)